S T U D I E S D I L a T a T I

E X P E R I M E N T A L S T U D I E S

0 N

A C U T E G A S T R I C D I L A T A T I 0 N

R. Wekselman, B. Sc., M. D.

Research Assistant in the Department of Experimental Surgery, Demonstrator in the Department of Anatomy, McGill University, Montreal, Canada.

A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the Degree of Master of Science.

August, 1961. McGill University. "When thus you pause in serious dubitation

You must then think of GASTRIO DILATATION • 11

Sir Zachary Oope. i

PREFACE

The author of this thesis enlisted in the Faculty of Graduate Studies at McGill University in July 1960. Dr. Stanley c. Skoryna, Research Director of the Department of Experimental Surgery, suggested that I undertake the study of "Acute Gastric Dilatation" on which some of the preliminary work has been carried out in the department. This happened to coincide with my personal interest derived from having previous training in Surgery. I also happened to read a press report of the case of one, Sharry Rubin (Time, December 1958), a 11 neurotic 11 New York girl who developed acute gastric dilatation following the ingestion of an abnormally large meal and died. The review of literature revealed that numer ous controversies exist on this subject, sorne of them based on older ill-founded views which do not stand the scrutiny of modern methods of investigation. It appeared also, that only a small amount of experimental work has been carried out on the subject recently, and that a reevaluation of the problem is needed. One particular aspect is worth mentioning and that is, that ii

acute gastric dilatation is a frequent condition in cattle and sheep, and that sorne elues as to its etiology may be derived from correlated studies. During the year of investigation at McGill University, I consider myself fortunate to have had advice from many members of the Departments of Surgery and the Basic Sciences. It has indeed provided me with an opportunity to learn not only the method, but also the significance of medical research and to appreciate its importance in clinical practice. I would like to thank Dr. D. R. Webster, Professor of Surgery at McGill University and Surgeon in-Chief at the Royal Victoria Hospital, for making the necessary arrangements and providing the facili ties on the study of gastric dilatation. The research project was under the supervision of Dr. s. C. okoryna, the Director of Research of the Department and Assistant Professor of Surgery. He originated this study and gave excellent guidance throughout the year. I'·1any of his thoughts have been used in expanding the thesis. Dr. C. A. Macintosh, Professor of Physiology, contributed several very constructive ideas on the physiology of the stomach, and suggested modifications iii

of the recording apparatus. Dr. li. G. B. Gi~bert, Chairman of the Department of Anaesthesia at McGill University has been very helpful in attending seminars on the subject and making several very useful and pertinent suggestions. Dr. D. s. Kahn, Assistant Professer of Pathology at McGill University, has also been very kind in reviewing the pathology of sorne of the specimens that were used in the study. Dr. D. G. Dale (D. V. M.), Assistant Professer of Animal Science at Macdonald College,has been very kind in making avail able the departmental and his personal library for the review of literature on gastric dilatation in animals. Dr. I Kwilecki, Assistant Professer of the Department of Pharmacology at the University of Ottawa, was very useful for her suggestions on the use of various phar macological compounds used in the investigation.

Dr • .D. A. Murphy (D. V. J.Vl.), presentl.y on the House

~taff of the Montreal General Hospital, has spent con siderable time with the author in reviewing the data on the development of gastric dilatation in cattle. Dr. P. Secoly, Medical Electronist of the Department of Physiology, suggested the modification for the channel recording apparatus. Mr. P. L. Rojowski (M.Sc.) iv

very skilfully constructed the necessary recording apparatus used in the study. Dr. P. Bryden, of the Department of Psychology, very kindly assisted in the statistical analysis of the resulta. I would like to thank Miss u. Murer who was very efficient in the management of the secretarial work and the correspondance on the subject, and Miss A. Watkins who cheerfully gave her time in pre paring the various biochemical and pharmacological solutions used in the experimenta. Mrs. L. Tripanova prepared excellent microscopie elides that were used in part of the study. I would also like to thank Mr. M. Farrel, Mr. J. Byers and Mr. s. Podymov for their kind assis tance in the experimental operations and in the care of the animale. It was a pleasure to have spent the year with the other Research Assistants in the Department who added sorne ideas and provided encouragement during the experimental year. They include: Drs. R. Beaudry, A. Becerra, R. Chari, A. Dukay, G. Elias, A. Legare, D. McSweeney, G. Prohaska and E. Wright. My gratitude goes to the University of Alberta, v

and its professors of the Faculty of Medicine under whom I studied as well as to the Misericordia Hospital In Edmonton and its Staff Men, under whom I interned, as their guidance and the training they provided was valuable for the preparation of this year of research. At last but not least, to my wonderful wife, Edna, without whose constant encouragement and under standing, it would not have been possible for me to reach this stage of my career. I am also very grate ful to her in having the patience in proof-reading and typing this thesis. vi

TABLE OF CONTENTS Page

PREFACE • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • i TABLE OF CONTENTS ••••••••••••••••••••••••••••• vi LIST OF TABLES AND ILLUSTRATIONS •••••••••••••• ix

OHAPTER I: INTRODUCTION ••••••••••••••••••••• 1 OHAPTER II: ETIOLOGIOAL FACTORS IN GASTRIO DILATATION IN MAN •••••••••••••••• 5 A. Anatomical Factors •••••••••••••••••••• 5 B, Physiological Factors ••••••••••••••••• 10 o. Idiopathie Gastric Dilatation ••••••••• 24 OHAPTER III: GASTRIO DILATATION IN ANIMALS •••• 26 A. Etiology of Bloat ••••••••••••••••••••• 27 B. Mechanism of Bloat •••••••••••••••••••• 29 O. Course of Bloat ••••••••••••••••••••••• 29 D. Therapy of Bloat •••••••••••••••••••••• 35 E. Prevention of Bloat ••••••••••••••••••• 36 OHAPTER IV: OLINICAL COURSE OF GASTRIC

1 DILATATION ••••••••••••••••••••••• 37 A. Symptoms and Signs of Acute Gastric Dilatation •••••••••••••••••••••••••••• 38 B. Laboratory Findings in Acute Gastric Dilatation •••••••••••••••••••••••••••• 39 vii

Page

c. Treatment of Acute Gastric Dilatation •• 43 D. Prophylaxie of Gastric Dilatation •••••• 46 E. Prognosis of Acute Gastric Dilatation •• 47

CHAPTER V: SPONTANEOUS GASTRIC RUPTURE •••••• 49 Note on Traumatic Rupture of the Stomacn •• 51 CHAPTER VI: PATHOLOGICAL FINDINGS IN ACUTE

GASTRIC DILA~TION AND SPONTANEOUS RUPTURE OF THE STQrtlACH • • • • • • • • • • • 53

CHAPTEh VII: MATERIALS AND ~ŒTHODS •••••••••••• 6L A. General Comments on the Apparatus Used •• 62

~. Apparatus for measuring the effects of acetylcholine on the contractility of the gastric wall ••••••••••••••••• 62

~. Apparatus for measuring the intralu minal gastric pressure by distension with knwon voluntes of fluid ••••••••• 66 B. General Comments on the Methods Used ••• 70 1. Hethod of study of the contractility of strips of gastric wall on the various experimental conditions ••••• 70 2. Method of study of the intraluminal gastric pressures by distending the stomach with fluid •••••••••••••••••• 71

C. Genera~ Commente on the Preparation of Various Groups of Experimental Animals.. 73

1. ~tudies on the gastric tonus under various experimental conditions ••••• 73 2. :studies on the influence of pantothenic acid and magnesium on the tonus of the gastric wall •••••••••••••••••••••••• 76 viii

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CHA~T~ VIII: EFFECTS OF C~TYLCHO~INE UPON

TID.; CON :J!RA ü

GAo:J!RIC WA • • • • • • • • • • • • • • • • • EFFECTS OF STENSIO.N BY

M~oUlŒ!J VO rŒS OF FLUID

UPON THE GA' RIC WAL~ •••••••• 92 A. Discussion of the Me hod of Conversion of Pressure to Radi and Longitudinal Force •••••••••••••••••••••••••••••••• 92 B. Effects of Distensio on the Wall of the whole otomach 94

1. ~xperiments on r s weighing 220 to 250 grams • • • • • • • • • • • • • • • • • • • • • • • • • 94

2. ~xperiments on r ts weighing 70 to 80 grams •••••••••••••••••••••••••• L07 0. Effect of Distensio on the Wall of the Ruminectomized o omach ••••••••••• ~18

CHA~T~R X: ONCLUSIONo •••••• .i2'(

BIBLIOGRAPHY • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 129 ix

LIST OF TABLES AND ILLUSTRATIONS Page

FIGURE I • Acquired duodenal ileus •••••••• 6

FIGURE II • Gastric dilatation aggravated by nasal oxygen ••••••••••••••••••• 21

FIGURE III • Cow suffering from bloat ••••••• 30 FIGURE IV • Escape of foamy ingesta from incised rumen •••••••••••••••••• 32

FIGURE V • Air-fluid levels in gastric dilatation ••••••••••••••••••••• 41 FIGURE VI : Barium-outlined dilated stomach. 42

FIGURE VII • Autopsy specimen of gastric dilatation ••••••••••••••••••••• 54 FIGURE VIII Gross specimen of dilated stomach •••••••••••••••••••••••• 55

FIGURE IX • Gross specimen of dilated and ruptured stomach ••••••••••• 56

FIGURE X • Perforation site of dilated stomach •••••••••••••••••••••••• 57 FIGURE XI : Perforation site of dilated stomach •••••••••••••••••••••••• 58 FIGURE XII : Apparatus for studying effects of acetylcholine ••••••••••••••• 63 FIGURE XIII : Diagram of apparatus for studying effects of acetylcholine ••• 64

FIGURE XIV • Diagram of apparatus for study ing effects of distension upon the stomach •••••••••••••••••••• 67

I : Effect of acetylcholine on normal stomachs ••••••••••••••••••••••• 80 TABLE No. II: Effect of acetylcholine on vagotomized stomachs ••••••••••• 81 x Page TABLE No. III: Effect of acetylcholine on ruminectomized stomachs • • • • • • • • • 82 TABLE No. TI: Effect of acetylcholine on stomachs of traumatized animals •• 83 TABLE No. V: Effect of acetylcholine on distended glandular stomachs • • • • 84 TABLE No. VI; Effect of acetylcholine on distended glandular stomachs of vagotomized animals • • • • • • • • • • • • • 85 FIGURE XV : Comparison of the effect of acetylcholine on various stomach preparations •••••••••••••••••••• 86 FIGURE XVI : Comparison of the effect of acetylcholine on various stomach preparations •••••••••••••••••••• 87 FIGURE XVII : Comparison of the effect of distension upon the stomachs of various experimental animals •••• lOO FIGURE XVIII : Comparison of the bursting points of various stomachs ••••••••••••• 101 TABLE No. VII: Effect of distension on normal stomachs •••••••••••••••••••••••• 95 TABLE No.VIII: Effect of distension on stomachs of vagotomized rats ••••••••••••• 97 TABLE No. IX: Effect of distension on stomachs of traumatized rats ••••••••••••• 103 FIGURE XIX : Post-mortem pictures of traumatized rat ••••••••••••••••• 105 TABLE NO. X: Effect of distension of stomachs of young rats ••••••••••••••••••• 108 TABLE No. XI: Effect of distension of magnesium deficient rats •••••••••••••••••• 109 xi

Page TABLE No. XII: Effect of distension of pantothenic acid-deficient rats ••••••••••••••••••••••••• llO TABLE NO. XIII: Effect of distension of traumatized young rats ••••••• 112 TABLE No. XIV: Effect of distension of traumatized pantothenic acid deficient rats ••••••••••••••• 113

FIGURE xx • Comparison of effects of distension of various stomach preparations •••••••••••••••••• 115

FIGURE XXI • Comparison of effects of distension of various stomach preparations ••••••••••••••••• 116 FIGURE XXII : Post-mortem pictu.re of vagotomized rat •••••••••••••••••••• 119 XV: Effect of distension of ruminectomized stomachs •••••• 120 TABLE No. XVI: Effect o .r distension of distended rumincetomized stomachs ••••••••••••••••••••• 121 FIGURE XXIII : Comparison of effects of distension of various stomach preparations ••••••••••••••••• 122 TABLE No. XVII: Comparison of Pressure and Force at point of rupture •••• 123 - 1 -

CHAPTER I INTRODUCTION

The clinical condition of acute gastric dilatation is of considerable importance to both surgeons and physicians because of the rather sudden onset and the frequently fatal outcome if one fails to recognize it immediately. Fortun ately, the event is rare, nevertheless it is serious and embarrassing because it develops usually as an unexpected complication. It is known to follow trauma, infections and particu larly surgical procedures. The incidence of gastric dilatation has decreased considerably since the introduction of methods of anaesthesia and of gastric intubation in abdominal procedures. However, it still remains a problem of unknown etiology in many of the cases studied. Acute gastric dilatation represents an extremely interesting condition from the physio logical point of view. It appears that at least two forms of gastric dilatation can be distin guished; in one, the dilatation is produced by - 2 -

various forms of mechanical obstruction at the pylorus or at the duodenum, with a simultaneous inhibition of the vomiting mechanism; in the second form, the cause of the dilatation appears to be physiological and manifests itself in the inability of the stomach to contract itself beyond a certain point. Why this should happen in some cases and not in ethers, representa a problem for future investigation. The significance of finding a solution to this problem extends also to the numerous cases in which the dilatation is not extensive as well as cases of paralytic ileus which follow surgical procedures. In the last two years, a number of drugs have been introduced which are supposed to alle viate or prevent the adynamie states of the gastroin testinal tract. None of these appears to be com pletely successful, and a considerable amount of work has to be carried out in order to assess the usefulness of various preparations as well as to suggest new avenues for a pharmacodynamie approach. The work embodied in this report representa only a modest beginning in this large field of - 3 -

research. In the first place, we have attempted ta establish an experimental method for the pro duction of acute dilatation of the stomach. This took a considerable amount of time and numerous modifications were necessary before the method could be standardized in a satisfactory manner. We have then proceded with an attempt of studying the various physiological states such as these following vagotomy and the administration of various compounds. We hope that the resulte obtained have contributed to the advancement of knowledge to this important field. It seems ta be not inappropriate at this time to conclude the introduction by quoting Sir Zachary Cope, and published in the 11 The Diagnosis of the Acute Abdomen": "The stomach is a viscus large and hollow vfuich eagerly receives the food we swallow And afterwards, or even as we feed Contracte or swells according to the need, Within those limites which, though vague they be Are taught by modern physiology. So when a persan over-drinks or -eats, The stomach this offence by warnings greets, For flatulence or epigastric pain, Heartburn and nausea follow in its train Until the owner of the part maltreated Vows that his sin shall never be repeated. - 4 -

But sometimes after trauma or infection Or operation, either or election But much more often, I need hardly mention, In cases needing urgent intervention, From final causes really still unknown The gastric muscles may lose all their tone. The viscus then may quickly reach a size Extremely big and hard to realize Filling the upper abdomen so tightly That it becomes distended and unsightly, Nay, sometimes, when neglected, swells until Almost the whole abdomen it doth fill."

• • • • • • • • • • "When thus you pause in serious dubitation You must then think of GASTRIC DILATATION. 11 - 5 -

CHAPTER II ETIOLOGICAL FACTORS IN GASTRIC DILATAT.LON IN MAN

A. Anatomical Factors. There are several well-known anatomical factors which will produce or contribute to the development of gastric dilatation. The mechanism operational in such cases obviously is not related to the so-called idiopathie gastric dilatation which develops for no apparent anatomical reasons. The basis of the anatomical production of gastric dilatation is related to sorne form of obstruction of the pyloric end o:r ~~he stomach, or points distal to it. Even then, gastric dilatation will not develop if the vomiting reflex is preserved. On the ether hand, the anatomical factors which are described below may contribute to a varying extent in the development of gastric dilatation. 1. Dragging of the mesentery of the small intestine is known to result in compression and consecutive occlusion of the transverse portion of the duo denum (Baroody, 1958). Such a condition may result from an abnormally long mesenterial attach- FIGURE I

Aort;.

Third part of -+--ttrlrlllllt Duodenum 3upclior ~uperi.or :t-,esentr;ric J.iesenteric Artc~ry Artery Sm&ll Intestine

Smt>ll Intestine Pclvic ."loor

A. The emall bowel is supported by the pelvic floor and c ...,using no pull on the SUpl'!riOr mesenteri.e a.rtery.

Bo The smalJ. b01•el is unsupporteo 0'\<Ô.n ta cicntriz::~tionof the m~s~ntery by glands. The. mosenterl.o vessels nO\<' COlHp·ess the thir':J. part of the duodem.un producing ileus.

11 (From A. Lee McGregor, 11A Synopsis of Surgical An~tomy• • Fig. 65, P. 67, E~gthEd~t~on.) - 7 -

ment which causes the descent of the small bowel into the pelvis (See Fig. 1) and a pull on the superior mesenteric artery (Canner, 1907). Another condition which might produce secondary gastric dilatation can be induced by the incar ceration or compression of the distal end of the duodenum between the root of the mesentery which passes in front of it, and the vertebral column which lies behind it. Apart from the abnor malities in the course of the mesenteric artery, according to Canner (1907) the condition is aggravated by a lax and flabby abdominal wall and the lack of intestinal contents such as is found in fasting and the excessive use of laxa tives. Canner has also drawn attention to the possible pressure effect of a consolidated right lung in cases of pneumonia. However, the last mentioned factor is unlikely to be of consider able etiological importance. 2. Congenital abnormalities of the pyloric end of the stomach, such as prepyloric gastric atresia can also be responsible for or contribute to the development of gastric dilatation. Two types - 8 -

of atresia are distinguished by Brown and Hertzler (1960): complete atresia and partial atresia. The imcomplete form is more common due to the incidence of pyloric stenosis; it is said to result from an imbalance between the longitudinal and circular musculatures of the pyloric canal. In cases of pyloric stenosis, the regression of the circular musculature (Froelich, 1906) which normally occurs in the first year of life, fails to take place. This results in narrowing of the pyloric canal. The associated spasm is probably

responsible for the so-called 11 projectile vomit ing". The preservation of the vomiting reflex in these cases accounts for the fact that usually no gastric dilatation develops. However, occa sionally a graduel increase in gastric volume has been observed. 3. Primary pyloric hypertrophy in adults is a condi tion in which the stomach distends occasionally. According to Skoryna, Dolan and Glay (1959), this form of hypertrophy is probably based on similar congenital neuromuscular dysfunction of the pyloric canal mechanism as in the infantile form. However, the action o.f secondary factors during adul t life, - 9 -

such as electrolyte imbalance, might be respon sible for the late occurence of symptoms. Occa sionally, the presence of an ulcer in the pyloric canal might lead to secondary hypertrophy. 4. Compression of the duodenum by external forces, such as panacreatic cysts or tumors, spinal defor mities as found in tuberculosis, extensive spon dylitis, or in tertiary syphilis. Pressure by a consolidated pneumonie lung may also occasionally produce the development of gastric dilatation. Other intra-abdominal conditions, including preg nancies and tumors, are also known to be the cause of distension of the stomach. In pregnancy, there is compression of the third portion of the duodenum by the arteriomesenteric pedicle, which pulls the duodenum into the pelvis and compresses it against the uterus (Riviere, 1960). 5. Enlargement of the stomach in cases of gastric dilatation, whatever the etiology may be, acts as a mechanical factor and aggravates the condition. After the stomach has reached a certain size, kinking and rotation at the pylorus prevents it from emptying (Moynihan, 1926). The enlarged - 10 -

stomach also displaces the small bowel into the pelvis with a result of further traction of the mesentery and compression of the transverse portion of the duodenum against the vertabrae, thus setting up a vicious cycle (Leigh, 1960). 6. Anatomical anomalies of the cardia may contribute mechanically for obvious reasons to the obstruction of vomiting and indirectly to the development of gastric dilatation if the distal end of the stomach is occluded, or seme ether physiopathological fac tors exist which cause gastric dilatation. It has been suggested by Canner (1907) that a valve-like action of the cardia develops, inhibiting the expulsion of gastric contents upwards, into the oesophagus and oral cavity. B. Physiological Factors. In gastric physiology, several factors are involved in eliminating the agents which otherwise might contribute to the development of gastric dila tation. These include the secretion of gastric juice necessary for the digestive process, the propulsion of the bolus of food by the normal peristaltic move ments and the elimination of gases by belcning. When - 11 -

these functions deviate from the normal, no obstruc tion is necessary in order for gastric dilatation to develop. Normal peristaltic activity is governed by vagal impulses and maintained by the action of the myenteric plexuses. The peristaltic waves occur at the rate of two to three per minute. The force of contraction of the smooth muscle depends upon its initial length, thus distension either by fluid or gas produces powerful contractions of the gastric wall. With increasing distension, a critical point is reached at which these contractions cease. Any further increase in the intraluminal pressure results in the perforation of the gastric wall. The chemical changes which accompany smooth muscle contractions are similar to those in striated muscle. Glycogen is broken down and lactic acid is produced. In relative anoxia, lactic acid accumu lates resulting in the decrease of contractility. The tonus of smooth muscle is defined by Best and Taylor (1961) as the relation between the length of muscle and the tension which it maintains. The change in tonus constitutes a change in its - 12 -

elasticity, and is inversely related to the average volume capacity of the stomach. Any factor which decreases the tonus, depresses peristalsis. Follow ing vagotomy, the stomach is hypotonie and the pro pulsive waves cease. Normally, after several weeks or months, the tonus and peristalsis are partially restored lBest and Taylor). Reverse peristalsis occurs under various conditions of irritation of the gastrointestinal tract and of other organs, under certain metabolic disturbances such as in hyperemesis gravidrum and under psychogenic conditions due to visual, olfac tory and unsavoury stimuli. Vomiting is a protective reflex that serves to relieve the gastrointestinal tract of its irri tating contents. It is governed by the vomiting center which is situated in the dorsal part of the lateral reticular formation of the medulla oblongata (close to and sometimes including the tractus soli tarius) tBest and Taylor). Efferen~ fibers consist chiefly of the phrenics, the vagi and the sympatntics as well as the skeletal nerves to the abdominal muscles, and the cranial nerves to the palate, the - 13 -

pharynx, etc. The afferent impulses are transmitted through a number of pathways, but chiefly by the vagal and sympathetic fibers of the stomach and other abdomi nal viscera. When the vomiting center is intact, the gastric contents will be regurgitated, thereby pre venting their accumulation and subsequent gastric dilatation. 1. Severe degrees of aerophagia has been observed in emotional states (Gillesby, 1956). In no:nnal indi viduals, there is a considerable amount of air present in the stomach; this is eliminated in the presence of a normally functioning oesophageal sphincter. In breathing against a closed glottis, a negative pressure of thirty centimeters of water is produced in the oesophagus and in the stomach. Under these circumstances, air can be drawn into the stomach if the oesophageal sphincter is open (Maddock, 1951). In cases of belching, more air is drawn into the stomach than is eliminated. According to Soveri (Gerber, 1955), infants swal low air during deglutition, hence the rationale in 11 burping 11 them post-prandially. In the presence of mechanical obstruction, there - 14-

may or may not be any distension depending upon the amount of air swallowed (Fine, 1933). The accumulation of fluid depends primarily upon the presence of gases, and , in the absence of food, the swallowed air is the only source of gaseous distention. 2. Overaction of the gastric secretory function as a result of parasympathetic hyperactivity, com bined with inhibition of relaxation of the pyloric sphincter (McRae, 1943) results in the accumulation of gastric juices. Stimulation of secretion of digestive juices is affected by the ingestion of food and of various secretagogues. In gastric hypersecretion, where the digestive juices accumulate in the stomach, a 11 third space 11 is formed into which fluid and electrolytes are lost, dehydration occurs, and shock may result. 3. Neurogenic factors:- The vagus nerve supports motor impulses to the gastrointestinal muscu lature by increasing the tone and motility. Stimulation of the vagus results in contraction of the muscularis and in relaxation of the sphincters. The sympathetic system inhibits - 15 -

peristal s through the splanchnics. Response to stimulation of either system depends on or is conditioned by the preceding state of activity of the gastric musculature. a. Vagotomy and its effects have been known for quite sorne time. Klemptner (1935) found that vagotomy does not produce complete gastric atony if the intrinsic plexuses are intact. The stomach is capable of peristaltic move ments if the latter is not affected. Although motor functions of the gastrointestinal tract can be carried out through these local nervous mechanisms, an increased demand on the motor functions appear to be dependant on the vagal supply (Duncan, 1953). According to Gold (Edwards, 1954), stimulation of the vagus first enhances and then inhibits the gastric musculature, producing a local paralytic ileus which may act as an initiating force in acute gastric dilatation. b. Paralytic ileus refers to the impairment of gastrointestinal peristaltic activity which is seen in inflamatory reactions of the peri- - 16 - toneum or accompanying trauma or infections which may be extraperitoneal or even extra abdominal. It may also accompany certain taxie states such as uremia, and in electro lyte imbalance expecially where potassium is deficient, (Moore, 1957). The intestinal musculature is actually paretic in that its contractile powers are temporarily reduced. According to r~loore ( 195 ·(), the il eus ordinarily is due to an excessive neurogenic interference, probably by way of the sympathe tic inhibitory pathways. It is well-known that no mechanical obstruction is needed to prevent gases and fluids from escaping from the stomach. Moreover, overdistension may exhaust the gastric musculature and result in dilatation. Paralytic ileus follows surgery and is prolonged by peritonitis. It is characterized by the lack of bowel sounds in the absence of cramping pains in a patient suffering from abdominal distension, vomiting and obstipation. The pain is constant and combined with abdominal tenderness and rigidity, and is either general or localized. - 17 -

4. Gastric dilatation following any form of trauma usually begins twelve to seventy-two hours follow ing injury. Sixty-five to seventy per cent of these cases occur in surgical patients of which forty-five per cent follow gastric operations. However, adequate nutrition, normal blood volume, correction of fluid and electrolyte deficits, intestinal intubation and antibiotic preparation • • 1 of the gastrointestinal tract will ··a_lfiirit~:h- the incidence of this condition. In the post-operative period, early ambulation and ether measures to restore peristaltic waves are of importance. The return of peristalsis is recognized by the presence of mild abdominal cramps and the passage of flatus (Frazer, 1959). In post-traumatic gastric dilatation, stress may play a subsidiary role. According to Carlson and Ortiz (1960), there is an increase in free 17- hydroxycorticoid level following surgery which reverts back to normal in two to six days. With subsiding adrenocortical function, the gastrointestinal secretions increase. Adrenocorticotrophic hormone used in the treatment and prevention of - 18-

acute dilatation, may have its effect by suppres sing the exaggerated gastric hypersecretion which occurs in this condition. According to Dragstedt (1931), trauma causes an increased activity of the somatic and visceral nerves resulting in a reflex inhibition of the vagus and a loss in tone of the gastric musculature, secretions accumulate, air is swallowed and disten sion occurs. 5. The 11 cast Syndrome", according to Leucatia (1950) and Waddell (1955), is defined as a sequence of events, including gastric dilatation which follow any form of external injury and it is believed to be more common in nervous individuals. The dila tation is believed to be due to the hyperextended position of the spine following the application of body casts and hip spicas, or due to the limita tion of respiratory movements of the abdominal muscles. In either case, two factors seem to be of considerable importance, an emotional factor which causes the individual to hyperventilate and swallow excessive amounts of air, and an anatomical one where the third portion of the duodenum is com pressed by the mesentery and the superior mesenteric - 19 -

artery. 6. Post-anaesthetic gastric dilatation is due to the depression of gastric musculature by the anaethetic agent. Gastric tone and motility are decreased in the third stage of anaesthesia (Johnson, 1942). Primarily, the peripheral gastric motor mechanism is affected, and the conductive mechanism of the sympathetic and parasympathetic systems are affected secondarily. The depth of anaesthesia is believed to be more important than the length in the production of gastric dilatation. The use of the curareform drugs produce muscle relaxation at much more superficial levels of anaesthesia, and therefore decrease the necessity for deep anaesthesia and diminsh the inci dence of post-anaesthetic dilatation of the stomach. However, large doses of muscle relaxants will cause atonia of the musculature. The action of the curareform drugs is not by prevent ing the release of acetylcholine, but by blocking its action by combining at the muscle sole plate and competing with it. The other muscle relaxants however, as decamethonium and succinyl choline, are - 20-

similar in structure to acetylcholine and act as depolarizing agents, and are therefore readily destroyed by the cholinesterases. Pre-anaesthetic medication with morphine (and atropine which is anticholinergic by its com petitive action with acetylcholine at the recep tor) however, prolongs the effect of the anaesthe tic as it increases the gastric emptying time presumably due to a resultant spasm of the pyloric sphincter. Depending on the rapidity of induction of anaes thesia, we have various degrees of air swallowing. In the unconscious patient, any form of respira tory obstruction such as the accumulation of bron chiai secretions and the relaxation of the tongue allowing it to fall back into the pharynx and causing a ball valve effect on the oesophagus, allowing air entry but preventing its exit (Bolt, 1959). Also, in positive pressure breathing with a mask or with an improperly inserted nasal catheter or intratracheal tube, air may be forced into the stomach causing a rapid distension (Marrs, 1958). This is seen more commonly in patients who have - 21 -

FIGURE II

INCORRECT

Method in which acute gastric dilatation may be aggravated by nasal oxygen. The above figure demonstrates the correct and incorrect ways of introducing nasal oxygen catheters.

(From Marrs et al, Annals of Surgery, 148 : 8 3 5 ' 1958 • ) - 22 -

received muscle relaxants prior to endotracheal intubation (Evans, 1959). In the post-anaesthetic period we occasionally encounter gastric dilatation in patients if any form of respiratory obstruction is present. This is seen more commonly in debilitated patients with residual deep anaesthesia, over-relaxation, and in any form of pre-operative intestinal obstruction where there is a splinting of the diaphragm and abdominal wall resulting in poor function of the accessory respiratory mechanism. 7. The excessive use of narcotics may also lead to gastric dilatation. Morphine and its derivatives have a depressant action on the gastrointestinal activity and causes constriction of the sphincters with a resulting delay in emptying. Its action is believed to be due to vagal stimulation. Other drugs, such as heparin (Verhague, 1957) have also been implicated in the production of gastric atony. Heparin has an antispasmodic as well as an anticoagulant effect. In the treatment of post operative thrombosis with heparin, Verhague (1957) found that gastric dilatation developped, however, - 23 -

the nature of this effect is not clear, as gastric hypotonia may have preceded the onset of anticoagu lant theraphy post-operatively. 8. Ingestion of effervescent compounds may also result in acute gastric dilatation. Other dietary indiscre tions, that is to say, after a single very large meal or the rapidity with which it is ingested, the ingestion of vegetables and copious water drinking play an important role (Conner, 1907; Bolt, 1959; Time, December 15, 1958). Decomposition of carbohydrate foods as seen in baby diets (Gerber, 1955) liberate large amounts of carbon dioxide, which if not eliminated, will result in gastric dilatation. 9. Chronjc or debilitBting diseases, starvation and emaciation may predispose to gastric dilatation when amounts of food which would be considered normal to

the healthy are ~-Lven to these individuals. This factor may be related to avitaminosis and to fluid and electrolyte imbalance. Shock is often associated with acute dilatation of the stomach. However, the problem is one which covers such a tremendous field that no more than a mere - 24-

mention of it as a contributing factor shall be attempted in this paper. All forms of shock are involved, and it is not certain whether this is the primary factor, or whether gastric dilatation is the cause of the loss of fluid and electrolytes. o. Idiopathie Gastric Dilatation. Idiopathie or spontaneous gastric dilatation is a very rare condition. The enlargement of the stomach is attributed ta the flaccidity of its muscu lature and the distension of the organ with gas. The source of the gas and the reason for failure of its elimination is obscure (Bolt, 1959). This condition has also been named "acute duodenal ileus 11 , "acute mesenteric ileus 11 and "arteriomesenteric ileus1' (lVIoyers, 1957).

Idiopathie gastric dilatation differs from post-operative dilatation by its spontaneous onset. It is more common in the mentally retarded; it is com rnoner in the third decade, and there is no sex inci dence although it has been reported more frequently in women than in men. Primary neurogenic dilatation of the stomach - 25 -

is due either to neurogenic or muscular paralysis, with a secondary occlusion by kinking of the duodenum or by the traction exerted on the arteriomesenteric pedicle resulting in compression of the duodenum (Borchgrevink, 1913). The obstruction develops secon darily and increases the severity of the condition. Failure of the eructation mechanism and of the vomit ing reflex acts as an additional aggravating factor. - 26 -

CHAPTER III GASTRIC DILATATION IN ANIMALS

Gastric dilatation is observed frequently in ruminant animals such as cattle and sheep. It is called 11 bloat11 or ntympany", and is defined as a form of indigestion, marked by an accumulation of gas in the forestomach or rumen. Other names such as 11 hoove", "hooven11 and 11 blomen 11 have been used as synonymerJ to describe the condition. f., Bloat develops in cattle feeding on lush, succulent green pastures, such as alfalfa and fresh elever tops, especially when wet. It is a seasonal problem and occurs more commonly in the spring when the animals are turned out to fresh pasture for the first time. It also occurs in the fall when the pasture is rejuvenated by the cool wet weather (Merck). The problem that bloat presents to agri culture are three in number (Dougherty, 1956): (a) the loss of cattle, as fifteen per cent of the affected cases terminate fatally, (b) the loss in milk production after the animal has recovered, and (c) the necessity of changing the kind of feed arises. - 27 -

A. Etiology of Bloat. The principle cause of bloat is unknown; but atony and paralysis of the rumen is due to overdis tension. In bloat, there is a defective eructation mechanism, and although belching is initiated, the gases are not expelled due to excessive froth forma tion (Blake, 1957). The rumen may increase in volume one hundred fold before causing death. A hereditary factor has been suggested in the etiology of bloat, but it seems that the condition will not occur unless other factors are present. Climatic conditions may play a role, but its exact nature has not been determined (Dougherty); however as already noted, geographie conditions do influence its incidence depending upon the type of pasture present. In cattle that are prone to bloat, the foam in the ruminal contents is stable and of a high vis cosity, and is responsible for the direct inhibition of the eructation mechanism. Crude rumen liquor contains antifoaming agents. Bloat develops if the acidity of the liquor, whose normal value is at a pH of six (Johns, 1958), decreases and the condition - 28 -

deteriorates. The bicarbonate-phosphate buffering system of the saliva probably prevents bloat by decreasing the fall of the pH of the ruminal contents. The formation of gases in the rumen may depend on the type of sugars present, and fermentation is due to the presence of yeasts in the rumen tNewsome, 1952). Carbon monoxide, hydrogen sulphide and cyanide poisoning may also contribute to the animal's demise. The stimulus in eructation is the same as that

in rumination, namely the mechanical irritat~on of the ruminal wall, (Dougherty). When the dietary intake lacks roughage as with fresh legumes, it is suggested that the loss of the mechanical irritation to the rumen wall contributes to the cause of rumen atony. This rather than the chemical composition of the rich legumes is incriminated in the causation of bloat. Raising the fluid level above the cardia caused by denser feed sinking to the floor will prevent the

escape of gas frcm the dome of the paunc~ and inhibit eructation and the froth is not belched efficiently. Drinking water at the time of feeding aggravates the condition tNewsome). Other factors such as cyanide poisoning, obstrue- - 29- tion of the oesophgus by swollen lymph glands in the thorax, and low-grade peritonitis have also been described as contributing causes in the etio logy of bloat (Nichols, 1956). B. Mechanism of Bloat. The mechanism of bloat has been partly dis cussed together with its etiology, however the factors of importance in animale can be listed as follows: (1) the eructation mechanism is directly inhibited by foam; (2) gases are formed in the fermentation process; these are retained within the foam preventing them from being eliminated by belching. Sorne of these gases, such as carbon monoxide and hydrogen sulphide, are extremely toxic to the animal; (3) foam, under normal condi tions, is broken up by antifoaming agents inher ently present in the rumen. As the pH decreases, these agents lose their effect, the foam retains its stability and cannot be eliminated, thereby producing bloat; (4) the rumen becomes overdis tended resulting in atony and paralysis. c. Course of Bloat. Bloat is usually manifested three days, and often twelve hours after feeding in fresh legume pasture, especially when wet (Boda, 1956). The - 30 -

FIGURE III

1 C:ow 77 dppro•irn .. telv IS minute\ preceding :1·- ·t.. Nvt•· that th<' rumen does not dppea:r partieu~ "' v d;stended even though the rumen prenure ••· ceeded bO mm. Hg.

tFrom Boda et al, Journal of the American Veterinary Medical Association, ~:532, 1956) - 31 -

physical appearance is quite variable. The animal stops grazing, it has a distressed countenance and an open mouth, there is exessive salivation, the feet are spread apart and the gait is unsteady(Merck) the respirations are increased in rate and then cease after a period of restlessness (Newsome). There is often a very extensive fullness of the flank, but this may be minimal depending upon the looseness of the hide (Boda). The animal may not appear very distended, and yet it may go on to die. It may bloat up to a hundred consecutive times before its final termination (Dougherty). It has been observed in bloat that the heart rate usually increases, but it may decrease and the animal expires. In severe cases of bloat, the mucosal membranes are cyanotic and the animal may die in a convulsive state. Both are probably due to anoxia. However, the bloat may persist for one or two hours and then subside, with the subsequent recovery of the animal. The effects of ruminal distension may be described as follows: 1. Effect on salivation: The salivary flow is increased. The salivary - 32 -

FIGURE IV

The escape of foamy ingesta from cow after the rumen had been opened with a knife. The free gas had pre viously been allowed to escape by tapping the rumen.

(From Boda et al, Journal of the American Veterinary Medical Association, ~:532, 1956) - 33 -

mucoproteins produce a stable foam. The saliva contains one hundred millimoles per liter of carbon dioxide which are released and add gas to the foam when the acidity of the salivais increased to equal that of the ruminal contents. The volume required to raise the pressure by ten millimeters of mercury decreases as the ruminal pressure increases; that is, with slight bloat, only a small amount of gas can aggravate the con dition • The increased pressure in the rumen causes an increase in parotid secretion; corre spondingly, there is an increased flow of sliva from the mouth. Progressive inflation of the rumen inhibits this effect. Inflation of the oesophagus alone stimulates the parotid secretion; inflation of the rumen alone inhibits this effect. These responses are independant of the neurogenic stimulus (Kay and Phillipson, 1959). Section of the vagus has been found to abolish the autono mie nerve impulses from the oesophagus, while section of the vagus at the level o1" the diaphragm abolishes the inhibitory impulses from the rumen. 2. Effect on eructation: This consists of three stages: {a) the free rumen - 34 -

gas is moved to the antrum of the cardia by contraction of the rumen, (b) the cardia relaxes to permit the gas to enter the oesophagus, and (c) the gas is eliminated by the relaxation of the cranial oesophageal sphincter and contrac tion of the oesophagus. Eructation is stimulated by distension of the rumen with gas. The receptors responsible for this phenomenon are situated in the posterior dorsal sac of the rumen or in the region of the cardia (Kay and Phillipson). The movements of the rumen and eructation exist in the early stages of bloat, but decreases in efficiency as the cardia is covered by partially digested food and the oesophagus fills with foam. Bloat is then precipitated and aggravated. 3. Effect on respiration and blood pressure: Inflation of the rumen slows or stops respira tion resulting in a decreased oxygen consumption and in decreased arterial oxygen levels and an increased fluctuation in blood pressure. In the early stages, there is a small and stepwise increase in blood pressure in proportion with the increased intraruminal pressure. This is due to - 35 -

obstruction by the inferior vena cava as the abdominal vena caval pressure is somewhat lower than the pressure within the rumen. In bloating animals, peristalsis occurs in the early stages, but as the rumen becomes overdis tended, it becomes atonie and paralyzed. The cause of death in bloat is not known, but it is believed to be due to the interference by the increased intraruminal pressure with the circulation and respiration. The absorption of toxic gases may play an important role in the animal's demise. On post-mortem examination, the lungs have been found to be congested, and punctate hemorrhages may be seen on the pericardium and pleura. Occasionally, the diaphragm may be rup tured. D. Therapy of Bloat. The treatment of bloat is an emergency and is mechanical in nature. The following measures have been advocated (Dougherty): (1) gastric intu bation, (2) trocaring the rumen together with adequate antibiotic coverage to prevent peritonitis, (3) forced movement by elevating the hind limbs, - 36 -

(4) rumenotomy should be resorted to for persistant cases in spite of the other measures as well as for recurrent cases, and (5) suportive measures with Tartar emetic, calcium gluconate and dextrose. E. Prevention of Bloat. The prophylaxie of bloat is much more impor tant than the treatment, as once the condition has occured, it presents several problems which are very difficult to cope with. The steps taken in the prevention of the condition have been described by Dougherty (1956) as: (1) avoiding turning hungry animals on fresh green pastures and watching them carefully when they are first pastured, (2) drench ing of the feed with turpentine with resulting defoaming effect, (3) administration of methyl sili cone, paraffine and peanut or soy-bean oil to pro mate a surface-binding action, (4) addition of straw or non-legumes to the feed to provide the necessary roughage to stimulate peristalsis and eructation, and (5) administration of penicillin in arder ta abolish the defoaming properties of the ruminal fluid; this measure is based on cutting dawn the intestinal microflora. - 37 -

CHAPTER IV CLINICAL COURSE OF GASTRIC DILATATION

In cases of acute gastric dilatation, the patient usually presents himself with a his tory of symptoms following the ingétion of a ,\ heavy meal (Bolt, 1959). The ingestion of vegetables and other substances containing readily liberated gas may precipitate the onset of symp toms. The liberated gas is believed to be carbon dioxide. Sodium bicarbonate with oopious water- drinking may bring on an attack which resul ts in rupture of the stomach. Acute dilatation may follow a history of chronic dilatation, in which an already weakened gastric wall is present; the sudden intake of a large amount of food will cause the progression of the condition. Dilatation of the stomach is most commonly observed in starvation. This is found in prisoner of war camps during World War II (Tanner, 1959). Gastric atony and a generalized malnutrition in these individuals probably pre dispose to the development of the condition. - 38 -

A. Symptoms and Signs of Acute Gastric Dilatation. 1. Pain is insideous in onset (Bolt, 1959; Conner, 1907), but episodes of painful crises may also be observed. The pain is localized in the epigastrium and the periumbilical region, and sometimes is associated with a feeling of epigastric fullness. 2. Vomiting without retching is an early and persistant symptom. The vomitus is watery at the beginning, greenish in color and scanty in volume. It gradually becomes more copious, feculent in odour, and brown in color due to the presence of blood. Occasionally the odor may be acid or sour-smelling. 3. Frequent and shallow respiration, possibly due to the limitation of the diaphragmatic excur sion. 4. Unguenchable thirst, probably due to the dehy dration and shock, may be accompanied by oliguria or anuria. The intake of a large aaount of fluid at this time causes the dis tension of the already weakened gastric wall. 5. Persistant hiccoughs may result from diaphrag matic or gastric irritation (Rundle, 1957). - 39 -

6. Skeletal muscle cramps. The cause of these is unknown. The author believes this to be a form of tetany resulting from the hyper ventilation. It is also known that hypo kalemic alkalosis due to persistant vomiting, resulta in the loss of potassium and causes muscle cramps. ?. Terminal shock and delirium result from an excessive loss of fluid and electrolytes. s. Physical examination does not reveal any change in blood pressure in the majority of subjects affected. The skin is frequently cyanosed and of mottled appearance due to the stasis of blood and decreased venous return. The abdomen appears distended, it is tender and rigid, and an enlarged stomach may be outlined by palpation and sometimes even seen. A succussion splash can be elicited by bimanual palpation. Bowel sounds are present in the early stages. B. 1aboratory Findings in Acute Gastric Dilatation. 1. Hemoconcentration due to escape of fluid into the dilated and paralyzed stomach. The hyper- - 40 -

secretion and non-absorption of gastric con tents contribute to the inoreased levels of hemoglobin and hematoorit. 2. Fluid and electrolyte disturbance is evident; there is a fourfold outpouring of secretions into the stomach which may approach eight hundred milliliters per hour, resulting in a rapid decrease in the oiroulatory blood volume and interstitial fluid. 3. Gastrio analysis shows equivooal resulta. According to some authors tVragstedt, 1922) achlorhydria is present and the levels or· lactic aoid in the stomach are increased.

According to others l~undle, 1957J the acidity

due to free nyaroc~oric ac1d is increased. The other contents of the gastrio aspirate are bile, pancreatic juice and duodenal secre tions. 4. Blood Urea Nitrogen levels are increased in spi te of normal renal function. This may be attributed to tissue necrosis. 5. Radiologically, a large gastric shadow is seen outlining the greater curvature. Air- - 41 -

FIGURE V

~upine decubitus and right lateral decubitus, adequately demonstrating an air-fluid level as seen in acute gastric dilatation.

(From Gillesby and Wheeler, The American Surgeon, ,gg:ll54, 1956) - 42 -

FIGURE VI

The stomach is occupying three-fourths of the abdominal cavity. The lower margin of the greater curvature is on a level with the pubic symphysis.

(From ~appel et al, American Journal of Digestive Diseases, E!:46, 1952.) - 43 -

fluid levels are present. C. Treatment of Acute Gastric Dilatation. In the treatment of gastric dilatation, several points should be considered, of which decompres sion of the stomach is the essential feature. To facilitate this, Moynihan (1926) found that the positioning of the patient in the knee-chest or in the Trendelenberg to bring the small intes tine out of the pelvis and to release the traction exerted on the superior mesenteric artery (Gold, 1952), or changing the position frequently pro vided considerable relief. 1. Gastrointestinal suction should be institued early. Considerable difficulty is encountered in the intubation, and often a failure to aspirate fluid from the stomach is encountered. This is explainable by the valve-like closure of the cardia due to ballooning of the stomach. A definite sign of decompression is manifested by a long rush of air as the tube enters the stomach, and not the aspiration of fluid as the fluid may come from the regurgitated gastric contents collecting in the esophagus (Wheeler, - 44 -

1959). Aspiration should be intermittent in order to prevent any sudden decompression. According to Gerber et al (1955) it is diffi cult to maintain fluid and electrolyte balance in the presence of a gastric tube, but this may be over-ruled as the possibility of intra venous infusions makes the maintenance of these patients on gastric suction a logical form of therapy. The routine use of gastric suction has been condemned by certain workers. In a clinical study on operated patients at the Los Angeles County Hospital, routine intu bation has been eliminated since 1956, and it was found that the return of peristalsis was not delayed. These patients were more comfort able, better fluid and electrolyte balance was maintained and less nursing care was required. Also, the incidence of respiratory tract infec tions in the non-intubated was three per cent as compared to fourteen per cent of those intu bated. In addition, suction tubes were found to be very irritating as demonstrated by the adherence of thick globs of mucus on their outer - 45 -

surfaces. 2. Parenteral fluid and electrolytes in the form of intravenous infusions to correct the imbalance. 3. Low enemas and rectal tubes to stimulate peris talais. 4. Parasympathomimetic drugs as prostigmine, and pantothenic acid have been found to provide relief in the presence of gas pains, the early return of peristalsis and the passage of flatus. Pantothenic acid is administered intramuscularly in dosages of two milliliters immediately; two milliliters repeated in two hours, then every six hours for twenty-four hours or until the return of bowel sounds (Pena, 1959). 5. Trocaring the stomach through the abdominal wall has been described in the early literature. This was carried out only if decompression through a gas tric tube was not successful. 6. Laparotomy should be resorted to only if the above described conservative measures fail and gastric dilatation increases. Gastrostomy in the procedure recommended, but the mortality is especially bigh. - 46 -

D. Prophylaxis of Gastric Dilatation. In individuals in whom acute gastric dilatation can be anticipated, prophylactic measures should be adopted. This applies to debilitated patients undergoing surgery, patients who have undergone severe trauma, patients with spinal deformities and those with a previous history of gastric dila tation. The following measures should be adopted. 1. Gastrointestinal intubation pre-operatively in all cases undergoing abdominal or thoracic surgery. After the tube has served its pur pose, it should be removed at the earliest possible date. Prolonged gastric suction makes the maintenance of fluid and electrolytes diffi cult and expansive. 2. Pre and Post-operative care in the form of correction of nutritional deficiencies and any fluid and electrolyte disturbances. 3. Mild sedation in fracture cases and in other orthopaedic affections requiring body and hip spi cas. 4. Endotracheal intubation in general anaesthesia in order to prevent insufflation of the stomach - 47 -

should controlled respiration become necessary in the course of the operative procedure. 5. Use of Pantothenic Acid after laparotomy. Thls compound was first used in England by Jacques in 1951 (Jacques, 1951) for the treatment of paralytic ileus. It was found that there was less distension, a lower incidence of nausea and vomiting and an earlier onset of peristalsis as compared to a group of controls (Haycock, 1951). 6. Early ambulation is effective depending of course on the post-operative condition of the patient. The ingestion of solids was claimed to prevent abdominal distension and gas pains (McPhail, 1958). E. Prognosis of Acute Gastric Dilatation. If not treated, gastric dilatation terminates fatally. Decompression becomes more and more difficult as the dilatation progresses, and the fixation at the oesophageal hiatus causes an acute U-shaped angulation at the cardia. The traction caused by the small intestine as it sinks into the pelvis (Fig. 1) draws taut the - 48 -

mesenteric vessels completing the obstruction (Wheeler, 1959). The patient becomes more aero phagie and a vicious cycle is set up. Results of operative intervention are discour aging due to the extremely poor condition of the patient and the irreversible changes that occur in the gastric wall due to the severe distension (Leigh, 1960). The mortality used to be as high as sixty to eighty per cent, but with the present knowledge in parenteral fluid therapy, the cor rection of nutritional deficiencies, treatment with gastric lavage and decompression, the mor tality is considerably decreased. The improve ments of modern anaesthetic techniques also greatly reduce the importance of the problem. - 49 -

CHAPTER V SPONTANEOUS GASTRIC RUPTURE

Acute gastric dilatation may go on to spontaneous rupture as a complication with a rapid and fatal termination (Leger, 1957). Spontaneous rupture of the stomach occurs under conditions where the organ is distended to such an extent that it is not capable of adapting itself to the tremen dous intraluminal pressure. Moore (1957) reported two cases of spon taneous rupture of the stomach in the new-born. He claims that fifty per cent are due to peptic ulceration. Other causes are due to defects of the gastric musculature near the cardia, or they may have sorne form of lower intestinal obstruction. The clinical signs of spontaneous rupture of the stomach can be summarized as follows: A. Abdominal pain which is initially unsteady and poorly localized, but commoner in the epigas trium. It may localize in the right upper quadrant in twelve hours. B. Subcutaneous emphysema due to the release of intragastric air into the subcutaneous tissue. - 50 -

c. Vomiting which is a reflex, and caused by the peritoneal soiling from the escaped gastric contents.

D. ~panitic abdominal distension due to peri tonitis and pneumoperitoneum; the distension with extreme rigidity and tenderness of the abdominal parietes are associated with the absence of bowel sounds (HeMine, 1957). E. Decreased liver dullness due to intraperi toneal air separating the liver from the anterior abdominal wall and diaphragm. F. Shock may be the presenting syndrome mask ing all other symptoms and signs. G. Fatal termination ensues if not treated immediately.

Hadiologica~ visualization of the abdominal cavity demonstrates the presence of intraperitoneal gas which is greater than in perforation of the lower intestinal tract. In infants, fifty per cent of spon taneous gastric rupture occur in pre-mature babies during the first week or ~ife, (Moore, 1957). At first the stool is normal and then there is a frank melena accompanied by hema- - 51-

temesis. With perforation, there is abdominal distension with dyspnea and cyanosis. Edema of the abdominal wall and flanks may be demonstrated. Immediate surgical intervention is indi cated in spontaneous rupture of the stomach after measures are taken to deal with the shock. The procedure involves laparotomy and gastroenterostomy together with peritoneal lavage and intensive anti biotic coverage. A soft rubber drain should be placed under the left hemidiaphragm before closure. Post-operative blood transfusions and parenteral fluids and electrolytes are given as needed. Naso gastric suction should be maintained for several days to protect the traumatized gastric wall from distension. Note on Traumatic Rupture of the Stomach. Traumatic rupture of the stomach is rare because the organ is protected in its upper segment by a strong thoracic cage and by a powerful group of abdominal muscles at its lower segment. It does occur in injuries of the abdominal wall after the ingestion of a large meal or large amounts of fluid (Mickaladze, 1960). The symptoms and signa are the same as in spontaneous rupture, but the diagnosis - 52 -

is simplified by a history of abdominal trauma shortly after food intake, or the localization of the blow over the area of the stomach (ReMine, 1957). The treatment in traumatic rupture of the stomach is the same as that for spontaneous rupture. The prognosis should be guarded as over seventy per cent d~e of severe shock and peritonitis asso ciated with trauma inflicted upon other organs. - 53 -

CHAPTER VI PATHOLOGICAL FINDINGS IN ACUTE GASTRIC DILATATION AND SPONTANEOUS RUPTURE OF THE STOMACH

The post-mortem examination in patients with acute gastric dilatation shows a stomach which is greatly distended and bent on itself (Conner~ 1907). The cardiac portion, being the larger of the two, extends downwards and produces a sharp U-shaped bend on the lesser curvature side. Occasion ally, the distension may involve the small intestine or the oesophagus. The wall of the stomach is thin ned out and the rugal folds may be partly effaced or completely absent depending on the degree of dilatati on. In infants with congenital prepyloric atresia, three main anatomie changes can be found: (1) obstruction to a single or a double diaphragm, (2) an area of mucosal atresia, and (3) complete segmental atresia of the gastrointestinal tract. The usual course of acute gastric dilatation is its fatal termination as a result of rupture of - 54 -

FIGURE VII

An autopsy specimen revealing marked gastric dilatation which developed over a period of eighteen hours.

(From Gi11esby and Wheeler, The American Surgeon, ~:1154, 1956) - 55 -

l!'IGURE VIII

Gross specimen showing marked gastric dilatation with no evidence of any obstructing lesion.

(From Gillesby and Wheeler, The American Surgeon, 2 ~ :1154, 1956 . ) - 56 -

FIGURE IX

An autopsy specimen of a case of acute gastric dilatation with spontaneous rupture of the stomach. - 57 -

FIGURE X

Autopsy specimen of spontaneous rupture of the stomach illustrating the site of perforation. The tear is located on the anterior surface near the lesser curvature. - 58 -

FIGURE XI

Autopsy specimen of spontaneous rupture of the stomach illustrating the site of perforation. The tear is located on the anterior surface near the lesser curvature. - 59 -

the stomach. The tear is usually found along the lesser curvature, in the region of the cardia (Miller, 1957). In this area, the rugal f'olds are parallel to the curvature; they disappear with dilatation, thus producing a punctus minoris resis tentiae. The stomach wall remains distended even after rupture. On microscopie examination of the wall of the dilated stomach, a hypersecretory state of the glandular elements can be found with a massive congestion of the vessels (Chippail, 1948). The muscle fibers are thinned out and torn in many places with areas of minute hemorrhage in the mucosa and submucosa. Following rupture, the microscopie picture is the same except for a further thinning of the muscle layer. The causes or death in gastric dilatation and spontaneous rupture are: A. Failure of reabsorption of the gastric and pancreatic juices with their essential contents of sodium, potassium and chlorides (Leigh, 1960). Of all the enteric juices, pancreatic juice is the most essential for life due to its potassium - 60 -

content. Tetany results from the hypochloremic alkalosis caused by the non-absorption of gastric juice (Dragstedt, 1939). B. Bilateral pulmonary collapse is associated with the elevation of the diaphragm (Bolt, 1959). After the stomach has been ruptured, the escape of air may penetrate into the thorax causing a pneumothorax. C. Severe circulatory imbalance is caused by the high intragastric pressure resulting in circulatory failure, tissue anoxia and. cyanosis (Bolt). D. Air embolism may be the cause of death in rupture of the stomach. The site of air entry is through the torn gastric vessels, through the damaged vessels in the connective tissue as a result of the dissecting action of the subcutaneous emphy sema, and through the liver sinusoids if the tear extends as high. Death results from cardiac failure since the frothy blood is compressed rather than expressed by the ventricles. Air emboli may also occlude the coronary and cerebral circulala tions. E. Reflex vascular derangements are evoked by the - 61 -

sudden release of pressure produced by the rupture of the distended stomach. - 62 -

CHAPTER VII MATERIALS AND METHODS

A. General Cornments on the Apparatus Used. 1. Apparatus for measuring the effects of acetyl choline on the contractility of strips of gastric wall. The apparatus used in the study of the influence of various concentrations of acetylcholine upon the amplitude of contraction of strips of gastric wall is illustrated in Figures 12 and 13. The apparatus comprises three sets of equipment: a. Constant temperature apparatus: ('

i. A thirty millimeter~ cuvetteâ wi th a two way stop-cock which is immereed in ii. A constant temperature bath which is

regulated by

iii. A thermo-regulator thermometer which controls

iv. A set of heatin'Coils which are connected to v. An automatic thermo-regulator switch which is plugged into an electric outlet. - 63 -

FIGURE XII

Recording apparatus used in the study of the effects of acetylcholine upon strips of gastric wall. - 64 -

FIGURE XIII

.;r~ ·.. 1.\TU~ for !!·:ASU.utiG tho lllFWll!IC: or ACE:!'YL CHOLllŒ on S'i'RIPS or STCf!ACH PlUPA!"L\TIOHS ,

T ...... ~ c."' .. " TO'l T'"'"'-"'CTIC"

~.. , .. ... oe 111 ooi JO•• (,ht(T fC'

Diagramatic representation of the recording apparatus used in the study of the effects of acetylcholine upon strips of gastric wall. - 65 -

which it delivers is equalized ta that of the bath. iii. A glass tube suspended above the thirty milliliter cuvette and dipping into it, serves as oxygen inlet and provides a means for attaching the strip of stomach wall ta its S-shaped lower end, through which a continuous stream of oxygen is bubbled in ta keep the bath well oxygenated. By turning the two-way stop-cock, the Tyrode's Solution from the reservoir is allowed ta run into and fill the thirty milliliter cuvette. By turning it in the opposite direction, the fluid is drained from the cuvette. c. Recording apparatus: i. A double-drum kymograph, whose speed can be regulated, was set at 12.8 millimeters per minute • • A levered writing pen attached to the specimen ta be studied, recorded the con traction of the strips of gastric wall. - 66 -

2. Apparatus for measuring the intraluminal gastric pressure by distension with known volumes of fluid.

~he apparatus used for the study of the vari ation of intraluminal pressure or the whole stomach with various increasing increments of volume, is a modification of that used for the study of the influ ence of acetylcholine on the contraction of strips of gastric wall. The apparatus, as il~ustrated in Figure 14, consists of the following three groups of equipment. a. Constant temperature apparatus: i. A constant temperature water bath, ii. A thermo-regulator thermometer, iii. A set of heating coils,

iv. An automatic thermo-regulator switch, v. A circulating pump. b. The perfusion apparatus has been omitted, and instead, a 250 milliliter cuvette with a one- way stop-cock has been substituted. Oxygen is bubbled in through a tubing which consists of a perforated ring at its termination that lies in the cuvette. The Tyrode's Solution in the cuvette is renewed at the onset of each experiment. - 67 -

FIGURE XIV

·.·d. th ?LUIJ .L.; Ûi8

T .. ( '~.MO . l'.t """' oll't"t>ll. ,->'1-0:f.I.M~ M(~ i'i\

s..-...... ~ ~. ~=====~~.~~~~~ 1"~111l•i.'1t'ltt..t:fl.. L.: .. , "'f'llr

. 5"1'A~t "' "bls.n!N.C1 s -4 !), : \tokf"IAL s,..•'-• •.- s~•M•u·"' TRE1"li\1\Ar~orl

Diagramatic representation of the recording apparatus used in the study of the effects of distension upon the intraluminal pressure and the radial and longitudinal forces exerted upon the stomach wall. - 68 -

vi. A pump circulates the water in the constant temperature bath to ensure its uniform temperature. When the switch on the thermo-regulator is turned on, it starts the circulating pump. At the same time, the coils begin to heat the water in the constant temperature bath. When the temperature in the bath reaches the pre-determined value of 37° Centigrade, the mercury in the thermo-regulator thermometer reaches the required level and breaks the circuit. After the water in the bath has cooled and the mercury level has dropped, the circuit is reestablished and the heating coils resume their work. b. Perfusion apparatus: i. A Tyrode's Solution reservoir is kept at a higher level in order to maintain a hydrostatic pressure. ii. A polyethylene tubing, the upper end of which is connected to the reservoir

the lm'ler portion is coiled and immersed in the constant temperature bath, so that the temperature of the Tyrode's Solution - 69 -

c. Recording apparatus: i. A transducer or electronic strain gauge, ii. A Sanborn Pressure Recorder which traces the intraluminal changes electrographically, iii. A 20 milliliter syringe which is connected to the strain gauge. The strain gauge is connected by a polyethy lene tube to a glass tube whose end is J-shaped and to which the stomach is attached and suspended into the 250 milliliter cuvette. Tyrode's Solution is injected with the syringe, through the transducer and into the specimen in order to affect its distension with known increases in volume. The increase in intraluminal pressure of the stomach is transmitted through the strain gauge and recorded electrographically. The pressure recorder is balanced at the beginning of each experiment and used at the sensitivities of 5x, lOx and 20x attenu ation, each being at fifty per cent of the sensitivity of its predecessor (i.e. 20x is half as sensitive as lOx, and lOx is half as sensitive as 5x). The experiment is begun with the attenuator set at 5x, and after the distending pressure raised - 70 -

to a point at which the deflection of the stylus penis off-scale, the sensitivity is halved so as to bring the pen back to scale. The electrographic tracing, after it was completed, was compared to a set of calibration lines for the three sensitivities and converted to intraluminal pressures with each increment of distending volume. B. General Comments on the Methods Used. 1. Method of study on the contractility of strips of gastric wall under various experimental conditions. The animals were killed instantaneously and a strip of the gastric wall was excised parallel to the lesser curvature measuring ten millimeters in length and two millimeters in width. This was sus pended with one end fixed to the S-shaped end of the oxygen supply tube, and the loose end of the strip attached by a thread to the levered writing pen. The preparation was then immersed in the constant temperature Tyrode's Solution bath which was kept well oxygenated. It was allowed to recover for thirty minutes before its spontaneous contractions - 71 -

were recorded on the kymograph drum. The kymograph drum was allowed to run for approximately three minutes, in order to establish a base-line, before acetylcholine was injected into the bath. Following this, the drum was allowed to move for another thirty seconds so as to record the maximum amplitude of contraction induced by the addition of acetylcholine. The drum was then stopped, and the strip of gastric wall was washed three times by emptying the bath and refilling it from the Tyrode's Solution reservoir. The strip was allowed to rest for thirty minutes before the procedure was / reported. Acetylcholine in concentrations of 10-6, -5 -4 -3 10 , 10 , 10 were used. 2. Nethod of study of the intraluminal gastric pressures by distending the stomach with fluid. The procedure adopted in the study of intraluminal gastric pressures under various experi mental conditions was one in which the entire rat's stomach was used. The intraluminal pressures were measured by distending the organ with known incre ments of fluid. Various mechanical pressure recorders - 72 - were tried, but none served the purpose. Finally, the electronic strain gauge with a Sanborn Pressure Recorder were adopted. The pressure variations were recorded electrographically, the tracings were com pared to the calibration curves from which exact pressure values were determined for each increment of distending volume. From the latter, the force exerted on the gastric wall and the tension were calculated. The isolated stomach is connected by the pylorus to a glass tube leading to the strain gauge. The oesophagus is ligated, and the preparation is immersed into the well-oxygenated Tyrode's Solution bath. The stomach is distended gradually with two millimeter increments of Tyrode's Solution, and the rise in intraluminal pressure is recorded. The pressure at which the stomach ruptures is noted. It was also attempted to record the exact point at which the peristaltic activity would cease, but a very large variation was found between the indivi dual specimens. Also, it was found in sorne cases that once peristalsis ceased, the further addition - 73 -

of fluid would result in rupture of the gland. From tnis, it was concluded that peristalsis continued right up to the bursting point. Initially, acetylcholine was injected into the bath after peristaltic action had ceased with the aim of restoring it. The only affect this had, was to produce a feeble contraction which increased the intraluminal pressure by one millimeter of mercury. The procedure, therefore, was also abandonned. o. General Comments on the Preparation of Various Groups of Experimental Animais. 1. Studies of the gastric tonus under various experimental conditions. The experimental animais used in this phase of the experiment were adult male rats of the Royal Victoria Hospital Strain, weighing between 220 and 250 grams. Several series were established by subjecting them to various experi mental procedures listed below: a. Control group; normal, healthy rats were used as controls in order to establish a base - line. - 74 -

b. Rats with excised forestomachs; the rationale behind the removal of the ruminal portion of the stomach was to create an experimental con dition that would simulate the human stomach as closely as possible. The operative pro cedure was as follows: The abdomen was entered through an upper incision. The stomach was exposed and the ruminal portion was excised. The transverse ridge was closed with a continu oua suture, care being taken that no leaks were present. The abdomen was closed and the animal was not used until a month later in order to allow complete wound healing. c. I:1echanical distension of the stomach wi th fluid; rats in which ruminectomy was carried out pre viously were used for this study. The abdomen was opened through a midline incision, the stomach was identified and the pylorus ligated. A polyethylene catheter was introduced into the stomach via the oral route. A second ligature was placed at the oesophago-gastric junction. Five milliliters of fluid were injected, in all cases and the polyethylene tube was removed and - 75 -

the ligature tightened. The abdomen was closed and the animal was sacrificed twenty four hours later. d. Vagotomized rats; the abdomen was opened through a midline incision and the oesophago-gastric junction was identified as well as the two vagi nerves. The vagi were sectioned and the abdomen closed. The animal was allowed to remain for four to six weeks before it was sacrificed for gastric pressure studies. e. Distension of the glandular stomach in vagoto mized rats; these animals were used one month after combined section of the vagus and resection of the ruminal portion of the stomach. The method used for distension was the same as des cribed previously. f. Rats subjected to Noble-Oollip drumming procedure; normal rats were placed in a Noble-Oollip Drum and subjected to a measurable amount or trauma. The drum is constructed in such a way that there are two baffles placed diametrically opposite each other. As the drum is revolved, the animal is picked up by one baffle, and when carried to - 76 -

the top of its trajectory it is dropped only to be picked up by the other baffle. The dis tance the animal falls is not great enough to cause any externa.L or inte.rnal hemorrhage nor any fractures. Damage to the central nervous system has also been found to be of no conse quence. The animals in this series have been subjected to eight hundred revolutions. 2. Studies of the influence of pantothenic acid and magnesium on the tonus of the gastric wall. The experimental animals used in the second phase of the experiment were male rats of the Royal Victoria Hospital nHooded Strain11 at the age of twenty-one days at which time they are usually weaned from their mothers. They were put on Pantothenic acid-deficient diets, on magnesium-deficient diets and on normal purina diets as controls, with thirty rats in each group. The initial weight at the time they were put on the special diets were noted, and they were weighed weekly in arder to determine and record their progress. At the end of six or seven weeks, which is the time it takes a male rat on a normal diet to - 77 -

attain its adult weight ranging from 220 to 250 grams, the animale were sacrificed and studied. The rats were subjected to various forma of treatment which will be outlined below. a. Normal rats, whose average age at this time (ten weeks) and weighing between 220 and 250 grams at the time of the experiment, were used as a control group to which the animale on the deficient diets were compared. However, the resulta here were found to coincide with the group of normal adult rats already studied. It was therefore not deemed necessary to tabulate the findings separately. b. Young rats were used for a second baseline as a weight control group. Their weights ranged from 75 to 95 grams at the time of the experi ment which corresponded to those of the animale on the deficient diets. c. Noble-Collip Drummed rats; these were subjected ta three hundred revolutions of the Noble-Collip drumming. d. Rats kept on pantothenic acid-deficient diet. Although these animale were adults with respect - 78 -

to their age, their weights ranged from 75 to 100 grams only. e. Pantothenic-acid-deficient rats subjected to Noble-Collip drumming procedure studied in order to determine the influence of trauma on the tonus of the stomach in these deficient animals. They also were subjected to trauma with three hundred revolutions of the Noble Collip Drum. f. Rats kept on a magnesium-deficient diet. Although these animale were also adults with respect to their age, they weighed only between 90 and llO grams at the time of the experiment. - 79 -

CHAPTER VIII EFFECTS OF ACETYLCHOLINE UPON THE CONTRACTILITY OF STRIPS OF GASTRIC WALL

In this study, the following groups were used: (1) normal healthy rats, (2) rats with excised forestomachs, (3) vagotomized rats, (4) rats sub jected to ischemie trauma, (5) vagotomized rats with excised forestomachs, and the converted glandular stomach distended mechanically with fluid, and (6) rats with excised forestomachs, and the remain ing glandular stomach distended with fluid. The procedures employed in preparing the above listed experimental groups were described in the previous chapter. The animals were sacrificed and strips of the gastric wall were excised and suspended in the perfusing solution. Acetylcholine was added to the solution in various concentrations. The contractions recorded on the kymograph drum paper are tabulated in Tables I to VI. It is evident from Figures 15 and 16 that only strips of normal gastric wall reacted to con centrations of acetylcholine as low as lo-7. - 80 -

TABLE I

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE ON THE AMPLITUDE OF CONTRACTION (in millimeters) OF STRIPS OF STOMACH FRür1 NORf'lAL RATS

Experiment Concentration of Acetylcholine Number lo-7 1o-6 1o-5 lo-4 1o-3 N - 1 4.5 3.5 6.5 7.0 11.5 N - 2 5.0 6.0 10.0 5.0 N - 3 4.0 6.0 6.0 10.0 N - 4 6.0 9.5 12.0 14.0 N- 5 6.0 15.0 13.0 N- 6 7.0 7.0 8.0 N - 7 2.0 5.0 7.0 9.0 N - 8 3.0 4.0 5.0 4.0 5.0 N - 9 3.0 4.0 6.0 7.0 8.0 N - 10 4.0 7.0 8.0 N - ll 2.0 4.0 5.0 7.0 N - 12 2.0 4.0 4.0 4.0 N - 13 4.0 5.0 6.0 9.0 N - 14 ,.o 3.0 6.0

Ivlean 3.9 5.3 6.1 7.6 8.4

Standard Deviation 1.82 3.14 1.77 2.88 3.51 - 81 -

TABLE II

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE ON THE AMPLITUDE OF CONTRACTION (in millimeters) OF STRIPS OF STOMACH FROM VAGOTOMIZED RATS

Experiment Concentration of Acetylcholine Number 10-6 10-5 10-4 lo-3 v- 1 4.0 6.0 7.0 11.0 v - 2 2.0 3.0 12.0 v- 3 3.0 4.0 7.0 19.0 v- 4 2.0 3.0 9.0 13.0 v- 5 4.0 5.0 7.0 8.0 v - 6 6.0 8.0 10.0 12.0 v- 7 6.5 9.0 11.5 16.5 v- 8 2.0 14.5 16.0 18.0 v - 9 8.0 12.0 18.0 23.0 v - 10 7.0 12.0 14.0 12.0 v - 11 3.5 8.0 13.0 11.5 v - 12 2.0 2.5 3.0 4.0 v - 13 1.0 3.0 6.0 11.0 v - 14 8.0 9.0 11.0 19.0 v - 15 3.0 4.0 5.0 7.0 v - 16 3.5 5.0 6;.0 7.5 v - 17 2.0 3.0 9.0 20.0 v - 18 3.5 4.5 7.0 9.0 v - 19 3.0 3.0 6.0 11.5 v - 20 3.0 6.5 10.0 11.0 v - 21 4.0 5.0 5.0 4.0 v - 22 3.5 3.5 2.0

Mean 3.8 6.2 8.5 11.9

Standard Deviation 2.06 3.44 4.11 5.53 - 82 -

TABLE III

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE

ON THE ~~PLITUDE OF CONTRACTION (in millimeters) OF STRIPS OF GLANDULAR STOMACH FRür'l RATS (in which the stomach has been converted to a glan dular stomach through resection of the forestomach)

Experiment Concentration of Acetylcholine Number lo-6 10-5 10-4 lo-3

G- l 4.0 4.5 5.0 9.0

G - 2 1.5 3.5 9.0 5.5 G- 3 2.0 4.0 5.0 9.5 G - 4 4.0 5.0 7.5 11.0 G - 5 2.0 2.5 4.5 5.5 G - 6 1.0 1.0 2.0 3.0

Mean 2.4 3.4 5.5 7.3

Standard Deviation 1.28 1.46 2.45 3.05 - 83 -

TABLE IV

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE ON THE AMPLITUDE OF CONTRACTION (in mi1limeters) OF ·STRIPS OF STOMACH FRür1 TRAUMATIZED RATS

Experiment Concentration of Acetylcholine Number lo-6 10-5 lo-4 10-3 T - 1 0.5 0.5 2.0 7.0

T - 2 3.0 6.0 8.0 9.5

T - 3 5.5 18.5 9.5 7.0

Mean 3.0 8.3 6.5 7.8

Standard Deviation 2.50 9 .. 22 3.97 1.44 - 84 -

TABLE V

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE ON THE AMPLITUDE OF CONTRACTION (in millimeters) OF STRIPS OF DISTENDED GLANDULAR STOMACH FROJ.Vl RATS

Experiment Concentration of acetylcholine Number 10-6 10-5 10-4 10-3 C-D - 1 2.0 3.0 4.0 7.0 C-D - 2 4.0 5.0 6.0 6.0 C-D - 3 2.0 3.0 3.5 8.0 C-D - 4 1.5 4.0 6.0 s.o C-D - 5 5.0 7.0 6.0 C-D - 6 2.0 3.0 4.0 5.0

Mean 2.3 3.8 5.1 6.7

Standard Deviation 0.97 0.98 1.43 1.21 - 85 -

TABLE VI

INFLUENCE OF VARIOUS CONCENTRATIONS OF ACETYLCHOLINE ON THE AMPLITUDE OF CONTRACTION (in millimeters) OF STRIPS OF DISTEI\TDED GLANDULAR STOMACH FROM VAGOTOMIZED RATS

Experiment Concentration of Acetylcholine Number 1o-6 lo-5 lo-4 lo-3 C-V-D - l 3.5 6.0 7.0 3.0 C-V-D - 2 2.0 7.0 8.0 11.0 C-V-D - 3 3.0 7.0 9.0 C-V-D - 4 1.0 2.0 2.5 C-V-D - 5 7.0 8.5 9.5 6.0

Mean 4.2 5.1 6.7 6.3

Standard Deviation 2.57 3.05 2.82 3.70 86

FIGURE XV

Am;Ht.\,l'lff or Contraetion lNFI.USNCE a! VAR1:Kf3 CONCF.l:ti./,T:;::nG of AC:;:y>.. CHGLn;~ on the .U.:i W'!".iJ.:. of C(;.Jli'ci:A~î:ON ot ;,ï'RI?S ot \'.... U~::_;,:, STO.l-L\.CH P1ŒPAiUTlOf.fS

-:.- ·..e:::: ., ~ 4stro;-ct.o~r'. 1.:.;;::-ec:.·>.~.,. "lallcto:!".,;: - 87 -

FIGURE XVI

D4"11181:Z tl

No-l f ov...,..., ...... ,. T,._UIO

In the group of animals which were vago tomized after previous resection of the forestomach and distention of the glandular stomach prior to the preparation of the strips, the amplitude of contraction increased with increasing concentrations of acetylcholine from 10-6 to 10-4 • The contraction induced by lo-3 concentration of acetylcholine was less pronounced than that induced by a concentration of lo-4• In the group of rats subjected to ischemie trauma by application of tourniquets to their extre~ mities prior to the preparation of strips of glandu 6 lar portion of the stomach, a concentration of 10- of acetylcholine induced the least contraction (average 3 millimeters). After the adminstration of a concentration of 10-5 acetylcholine, the highest amplitude of contraction could be observed, averaging 8.3 millimeters as compared to the concentration of lo-6. It is interesting to note that a still higher concentration of acetylcholine (lo-4) resulted in a decreased amplitude of contraction, averaging 6.5 millimeters. Whether the concentration of acetylcholine of 10-5 representa the dose which pro- - 89 -

duces maximal contractions or whether the decrease in response after the administration of a still higher dose is due to an exhaustion phenomenon, it cannot be stated with certainty. In the group of rats which have been pre viously vagotomized, the forestomach resected and the remaining glandular stomach distended with a constant volume of fluid for twenty four hours, a decrease in the amplitude of contraction could be observed after the highest dose (10-3) as compared to the lower concentrations (lo-6, l0-5 , 10-4 ) of acetylcholine. It appears therefore, that the vagotomized glandular stomach is incapable to react with an increase in cont rac t 1'l't 1 y t o d oses h'1gner ' than lo-4. However, when vagotomy was performed in animals in which the rumen was present, the usual increase in the amplitude of contraction paralleling higher concentrations of acetylcholine was seen. It seems logical to presume that the forestomach plays an important role in the capacity of the stomach to distend. This is in agree ment with the well-known fact that animals which pos- sess the ruminous portion of the stomach, the disten sibility is much greater as compared to man. In - 90 -

cattle for instance, the rumen may distend up to twenty times its original volume without perforating (Dougherty, 1956). It might be indeed that such a mechanism representa a safety valve in these species which is related to the type of feed ingested. In the remaining groups of animals (normal rats, rats subjected to excision of the forestomach and subsequently distended with a standard volume of fluid) the response to acetylcholine parallels the increase in dosage. In normal animals, the amplituae of contraction averaged 3.9 millimeters after a dose of 10-7 was administered and increased gradually, approximately by 1 millimeter with each tenfold increase in dosage up to an amplitude of 8.4 milli meters after a dose of 10-3• This was the highest dose of acetylcholine tested. The removal of the forestomach has resulted in a decrease in the amplitude of contraction which 6 averaged onJy 2.4 millimeters after a dose of 10- • This decrease was not maintained after higher doses of acetylcholine, and a dose of 10-3 produced an amplitude of contraction which averaged 7.3 millimeters. It appears therefore that the glandular stomach has - 91 -

a lesser capacity for contraction at the lower doses of acetylcholine than the normal stomachs. However, this seems only to be a question of threshold level as the response of the glandular to a high dose of acetylcholine (lo-3) was only somewhat lesser that of the normal stomach. The distension of the glandular stomach with a standardized amount of fluid seemed to have little effect on the response to acetylcholine. This is evident by comparison of this group of animals with that in which the forestomach was resected, but the glandular stomach was not distended. The responses to acetylcholine were approximately equal in beth these groups, averaging 2.3 and 2.4 millimeters after the administration of a dose of lo-6, and 6.7 and 7.3 millimeters respectively after the administration of a dose of 10-3• - 92 -

CHAPTER IX EFFECTS OF DISTENSION BY MEASURED VOLUMES OF FLUID UPON THE GASTRIC WALL

A. Discussion of the Method of Conversion of Pressure to Radial and Longitudinal Force. In studying the effect upon the gastric wall by distending the stomach with known volumes of fluid, it was attempted to determine both the intraluminal pressure at which peristalsis ceased as well as the intraluminal pressure at which the organ ruptured. However, it was found that in the majority of cases, peristalsis does persist to the point at which the intraluminal pressure was reached at which the gastric wall ruptures. Therefore, in further studies, only the last value was taken into consideration. The maximum pressure recorded is the value beyond which any further injection of fluid would result in the rupture of the organ. The deflections of the recording stylus pen were compared to the calibration curve and the trac inga were converted into values of pressure in terms of millimeters of mercury. From these, the radial - 93 -

radial force and the longitudinal force exerted upon the gastric wall were calculated according to the following formulas: 2 (1) A = 4 TI r

2 (2) or 3V = 4 TI r ; where A is the inter.nal area and r the radius. The ratio of the volume V to the area A is ~ r. The total force F equals PA, where P is the pressure and A is the area of the wall.

By equating formulas (1) and (2), 3V =A ; and, sinoe F- PA, by substituting for A we derive (3) F = 3VP Also, the longitudinal force exerted along the wall 2 is represented by F' =TI r P; and by substituting with formula (1) we derive the following formula: (4) F' = Îyp 4 or t o.f the force exerted radially upon the wall. The values of force have ta be mul tiplied by a constant of 1333.2 to convert them into dynes per square centimeter. These same formulas have been used by Burch et Al (1952) ta calculate the force exerted - 94 -

upon the cardiac wall at systolic and diastolic pressures. It was therefore felt that these formulas would also be applicable in this case. Therefore, the radial and longitudinal forces were calculated for each distending volume and the corresponding intraluminal pressure. B. Effects of Distension on the Wall of the Whole Stomach. 1. Experiments on rats weighing 220_to 250 grams. Sixteen rats were used for establishment of a control group for further experimental groups. The average intraluminal gastric pres sure in this group was 2.8 millimeters of mercury prior to the injection of a standardized volume of Tyrode's Solution (2 milliliters). After injection of two milliliters of the solution, the mean volume of the intragastric pressure was 5.6 millimeters of mercury. The mean value of the radial force exerted upon the gastric wall was 0.44 x 105 dynes/cm. 2 and that of the longitudinal force was 0.11 x 105 dynes/cm. 2 • Further increases of the radial and longitudinal forces were propor tional to the increase of intraluminal pressure - 95 -

TABLE VII

EFFECT OF INTRALUMINAL PRESSURE (in millimeters of mercury)

WITH DISTENSION OF THE NORMAL ISOLATED RAT'S STOMACH BY ~TER

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc N - 1 13.0 17.5 19.0 22.0 23.5 24.0 27.5 N - 2 0.5 4.5 8.5 11.5 13.0 17.0 34.0 34.0 39.0 N - 3 4.0 6.0 7.5 a.o g.o 9.5 10.0 11.0 13.0 N- 4 3.0 4.0 6.0 7.5 11.0 14.0 18.5 21.0 23.5 N - 5 3.0 5.0 6.5 8.0 8.0 8.0 8.0 9.5 12.0 N- 6 2.0 5.0 7.0 8.0 10.5 14.0 16.5 18.0 20.0 N- 7 0.5 4.5 5.3 15.0 17.0 35.0 28.5 30.5 N- 8 2.0 9.0 8.0 9.0 9.5 9.5 12.0 15.5 18.0 N- 9 2.0 3.0 3.0 4.0 5.0 5.0 6.5 6.5 7.0 N - 10 2.5 5.0 5.5 6.0 7.0 8.0 9.0 11.5 13.0 N - 11 4.0 5.0 6.0 7.0 8.5 9.0 8.0 10.0 .o N - 12 5.0 7.5 9.0 9.0 9.0 9.0 9.0 9~0 10.0 N - 13 2.5 5.0 6.0 6.5 7.0 7.5 10.0 13.0 17.5 N - 14 1.0 7.5 11.5 13.0 14.0 lf;.O 19.0 9.5 14.0 N - 15 2.5 3.5 4.0 6.0 6.0 7.0 8.0 9.0 10.5 N - 16 8.0 10.0 10.5 11.0 16.0 19.0 20.0 23.0 27.0

Mean 2.8 5.6 7.3 9.0 10.6 13.1 14.5 15.9 17.5

Standard Deviation 1.91 2.00 2.68 3.58 4.12 7.5q 7.24 8.32 8.60

Radial Fo ce o.oo 0.45 1.17 2.16 3.39 5.24 6.96 8.90 .20 (xlO 5 dynes per cm.2) - 96 -

TABLE VII (Continued)

Experiment Volume Injected Number 18 cc 20 cc 22 cc 24 cc 26 cc 28 cc 30 cc 32 cc 34 cc

N- 1 34.5 39.5 53.5 63.3 77.5 80.0 91.5 N- 2 46.0 65.0 N- 3 16.0 20.0 24.0 31.0 36.0 N - 4 27.0 32.0 46.5 51.0 62.5 75.5 92.5 103.5 N - 5 14.0 18.0 21.0 29.0 32.0 N - 6 34.5 39.0 N- 7 N- 8 23.0 35.0 35.5 42.0 .N - 9 a;5 10.0 12.0 15.0 20.0 23.0 25.0 40.0 N - 10 16.0 20.0 33.0 42.0 N - 11 11.0 14.0 19.5 6.0 10.0 20.0 N - 12 11.0 12.0 12.0 14.0 16.0 20.0 25.0 31.0 41.0 N - 13 20.7 28.0 48.5 48.5 N - 14 12.5 19.0 26.0 33.0 38.0 43.0 59.0 63.0 N - 15 14.0 16.0 20.0 23.0 N- 16 29.0 37.0 47.0 59.0 60.0

Mean 21.2 27.0 30.7 35.2 39.1 43.6 58.6 59.4 41.0

Standard Deviation 10.92 14.59 14.38 17.78 23.09 27.86 33.50 32.36

Radial Fo5ce 15.26 21.60 27.01 33.79 40.66 48.83 70.31 76.02 55.75 (xlO dy~es per cm. ) - 97 -

TABLE VIII EFFECT OF INTRALUMINAL PRESSURE (in millimeters of mercury) WITH DISTENSION OF THE VAGOTOivliZED RAT' S STOI"lACH BY WATER

.b:xperiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc v- 1 4.0 6.5 8.5 10.0 14.0 17.5 20.0 20.0 v- 2 1.5 5.0 8.5 11.5 13.0 14.5 17.5 20.5 v- 3 5.5 11.0 14.0 17.0 28.0 36.5 43.5 46.0 v - 4 1.0 2.5 7.0 17.0 21.0 22.5 24.0 26.0 v - 5 4.5 8.0 17.0 18.0 46.5 v- 6 1.0 5.0 40.5 40.0 v - 7 1.5 8.5 15.0 17.0 21.5 27.5 34.5 36.0 v - 8 3.0 7.0 19.0 17.0 20.0 20.0 22.0 16.0 v- 9 1.0 11.0 20.0 26.0 41.0 52.0 v - 10 4.0 7.0 8.5 10.5 13.7 18.0 22.5 28.5 v- 1.0 8.5 12.5 13.0 13.0 13.0 13.0 14.0

I-1ean 2.5 7.3 15.5 17.9 23.2 24.6 24.6 25.9

Standard Deviation 1.67 2.55 9.44 8.60 11.94 12.53 g.8o 10.80 Radial Force o.oo o~sa 2.48 4.29 7.42 9.84 11.81 14.50 \xlo5 dy~es per cm. ) - 98 -

TABLE VIII (.Continued)

Experiment Volume Injected Number 16 cc 18 cc 20 cc 22 cc 24 cc 26 cc 28 cc 30 cc 32 cc v - 1 23.0 24.5 28.5 34.0 43.0 56.0 69.5 79.5 93.0 0 v - <- 27.5 34.5 44.4 50.0 60.0 78.0 v - 3 48.0 49.0 52.5 54.5 57.5 55.2 42.5 44.5 51.5 v - 4 28.5 40.5 56.0 59.0 77.5 99.0 v - 5 v - 6 v - 7 44.5 48.0 48.0 v - 8 19.0 22.0 22.5 22.0 27.5 23.0 2g.5 30.0 33.5 v - g v - 10 36.0 45.0 52.0 55.0 60.0 65.0 80.0 80.0 80.0 v - 11 16.0 17.0 19.0 24.0 31.0 42.0 53.0 58.0 58.0

r.J:ean 30.3 35.1 40.4 42.6 50.9 59.8 54.9 58.4 63.2

Standard Deviation 11.61 12.53 14.73 15.62 17.90 24.49 20.28 21.86 23.54

Radial Fo;ce 19.39 25.27 32.32 37.48 48.86 62.19 61.48 70.07 80.89 (xlO dynes per cm. 2) - 99 -

TABLE VIII (Continued)

Experiment Volume Injected Number 34 cc 36 cc 38 cc 40 cc 42 cc 44 cc v - 1 v- 2 v- 3 51.5 51.5 51.5 34.5 20.0 16.5 v - 4 v - 5 v- 6 v - 7 v - 8 35.5 41.5 35.5 41.4 43.0 45 .o v- 9 v - 10 110.0 v - 11 61.0 64.0 73.0 80.0 110 .. 0

Mean 64.5 52.3 53.3 53.0 57.7 30.7

Standard Deviation 32.11 11.27 18.82 24.50 46.76 20.15

Radial Fo~ce 87.71 75.30 81.01 83.19 16.93 54.03 (xlO dynes per cm.2) - lOO -

FIGURE XVII

(Rats weighing 220 - 250 grarns)

1 1 1 1 1 1 1 20 .. 10 ~ 1 1

70•10 '

iS • 10 1 ' 1 1 1 1 1 iO • to' 1 1 1 1 1 1 1 1 :/B1

/ A 1 1 1 1 ' /

1 1 •

0 10

Volume (Milliliters) EFFECTS OF DISTENSION UPON THE STOMACH WALL OF VARIOUS EXPERIMENTAL ANIMALS

Legend A Normal rats A' - Rats with ruminectomized stomachs B Noble Collip traumatized rats B' - Rats with distended ruminectomized stomachs C Vagotomized rats 0' - Vagotomized rats with ruminectomized stomachs - 101 -

FIGURE XVIII

~ ,_ -:-11lir 'l'rr.,ur..a

?J x 1J5 t-l C\1- 0 s• erg 0 < lS x 1-h (l{) x 1-G-- - """-Cf.l ct !:orr,:ü jo:::! Q) p. ~ 1-'• :>., p .._,~ 50 x lji e Q) ':9 0 0 H h) x 1·:5 10 x loS 1'1 0 0 f%.1 Cl) r-iro ,...... •r-i 30 x 105 ~ rdro !:l p:; Cl) U1 20 x 105 ·:x loS """- 0s • ...._,.1\) 10 x 105

COMPARISON OF BURSTING POINTS OF STOt1ACHS OF THE VARIOUS EXPERIMENTAL ANIMALS - 102 -

following the injection of each additional two milliliters of the solution. At the bursting point, the mean pressure was found to be 92 millimeters of mercury and the radial and longitudinal forces aver aged 50.94 x 105 and 12.74 x 105 dynes/cm. 2 respectively. In the eleven rats which have been vagotomized four to six weeks prior to the carrying out of the experimenta, the stomach was found to be grosR1y djs- tended and filled with food and fluid although all animale were fasted for twenty-four hours prior to the procedure and in sorne cases up to seventy·-tvto hours. A definite loss of the tone of the gastric wall as well as the small bowel could be observed. In three of the animals, the rupture occured after the injection of eight ta ten milliliters of Tyrode 1 s Solution. The average intraluminal pressure recorded was a mean of 46 millimeters of mercury. In the remaining eight rats, the rupture of the stomach occured at the mean volume of 65.3 millimeters of mercury; the mean radial and longitudinal forces were 74.67 x 105 and 18.67 x 105 dynes/cm. 2 respec tively. - 103 -

TABLE IX

EFFECT OF INTRALUJYIINAL PRESSURE (in mi1limeters of mercury) WITH DISTENSION OF THE TRAU!YIATIZED RAT' S STOMACH BY WATER

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc T - 1 1.5 4.5 9.5 14.0 16.5 18.0 22.5 29.0 34.5 T - 2 1.5 3.5 7.0 11.5 14.5 16.5 17.2 19.0 19.0 T - 3 0.5 1.5 8.5 11.3 13.7 15.5 17.3 19.0 20.7 T - 4 0.5 3.5 8.5 13.0 15.5 17.5 17.5 17.5 19.0 T - 5 1.5 3.5 8.5 13.0 13.0 15.5 16.5 17.0 17.0 T - 6 1.5 3.5 6.0 9.5 12.0 13.0 14.5 16.5 19.0 T - 7 2.0 4.5 8.0 10.5 11.5 13.5 15.0 18.0 20.5 T - 8 1.5 5.5 9.5 11.5 15.5 22.5 31.0 43.5 65.5 T - 9 1.5 5.0 9.5 11.5 14.0 14.7 15.5 21.5 23.5 T - 10 7.0 11.5 15.0 17.0 20.0 27 .o 30.0 42.5 55.0 T - 11 0.5 2.5 7.0 9.0 9.0 11.5 13.0 15.5 18.5 T - 12 0.5 3.0 6.0 8.0 10.0 10.0 11.0 13.0 16.5 T - 13 0.5 3.5 6.0 8.0 9.5 11.0 15.5 21.0 29.5

Mean 1.6 4.3 8.4 11.4 13.4 15.9 18.2 22.2 27.4

Standard Deviation 1. 72 2.41 2.39 2.53 3.10 4.73 6.08 9.94 15.58

Radial Fo5ce 0.00 0.34 1.34 2. 74 4.29 6.36 8.73 12.43 17.53 (x10 dy~es per cm. ) - 104 -

TABLE IX (Continu ed)

Experiment Volume Injected Number 18 cc 20 cc 22 cc 24 cc 26 cc 28 cc 30 cc 32 cc 34 cc T - 1 53.0 64.5 80.0 T - 2 20.0 20.7 21.5 24.0 26.8 30.0 35.0 42.5 47.2 T - 3 24.0 30.0 38.8 42.5 53.5 65.5 86.5 92.5 100.0 T - 4 21 .5 26.0 29.5 38.5 47 .o 58.0 71.0 80.0 T - 5 18.0 19.0 21.5 26.0 32.0 43.5 51.5 59.7 63.0 T - 6 20.5 22.5 33.0 49.0 53.0 59.0 72.0 85.5 T - 7 24.0 29.5 38.0 48.5 57.0 61.5 67.0 73.5 73.5 T - 8 76.5 T - 9 31.5 49.0 59.0 62.0 T - 10 67.5 72.5 T - 11 23.0 30.0 33.0 46.0 61.0 93.0 T - 12 15.5 24.0 32.0 40.0 52.0 58.0 62.0 80.0 T - 13 38.0 47 .o 63.0 83.0

r1ean 33.1 34.8 39.6 45.6 49.4 58.5 63.6 73.4 70.9

Standard Deviation 20.10 17.40 17. 16.80 12.31 18.07 16.47 17.03 22.16

Radial Fo~ce 23.83 27.73 34.84 43.77 51.37 65.51 76.31 93.94 96.41 (xlO dynes per cm. 2) - 105 -

FIGURE XIX

Post-mortem specimen of an adult rat which had been subjected to eight hundred revolutions of the Noble-Collip Drum. The stomach is seen to be markedly dilated. - 106 -

Out of thirteen rats subjected to Noble-Collip drurnming, only in three was the distension evident to an appreciable extent, although in all animals of this group, a certain flabbiness of the gastric wall was found. The average intraluminal gastric pressure in these animals was lower at the zero point, but considerably higher at the point of rupture than that of the controls (78.6 millimeters of mercury as com pared to 42.3 millimeters of mercury). The radial and longitudinal forces were 86.26 x 105 and 21.56 x 105 dynes/cm.2 as compared to values of 50.94 x 105 and 12.75 x 105 dynes/cm.2 respectively in this group and in the normal group respectively. The values found in this group of animals are approximately 70 per cent higher than in the controls. It appears therefore that in the majority of vagotomized animals, a considerably higher intralu minal pressure is necessary to achieve the bursting point than in the controls. This is apparently due to the previous dilatation of the stomach which follows vagotomy. The earlier bursting point observed in the three vagotomized rats can be explained by hypertoni city of the gastric wall developped for an unknown - 107 -

reason. Following vagotomy, we have an unopposed action of the sympathetic stimuli which inhibits gastric tone and motility (Cobo, 1959). It has been found in experimente on sheep that partial vagotomy resulted in a transient decrease in the major ruminal movements for one to two days, while total vagotomy resulted in the complete arrest of the ruminal movements and the stomach became atonie (Duncan, 1953), and distended. In the animals subjected to Noble-Collip drum ming, the bursting point was still more delayed than in the vagotomized rats. This may be explained by the fact that greater volumes of flujd have to be injected into the stomach to produce the rupture of the muscle coat, in which tonus is considerably decreased. 2. Experiments on rats weighing 70 to 80 grams. In this series of experiments the effects of pantothenic acid and magnesium-deficiency respectively were studied, since animals of both groups weighed 70 to 80 grams at the time the procedure was carried out. Naturally, the group of control rats had to be selected within the same·weight range. - 108 -

TABLE X

EFFECT OF INTRALUMINAL PRESSURE {in millimeters of mercury) WITH DISTENSION BY FLUID OF STOMACHS FROM NORMAL YOUNG RATS

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc NY - 1 1.0 3.5 5.5 9.5 17.5 23.0 NY- 2 0.5 3.0 5.5 g.o 13.0 23.0 NY- 3 0.5 4.5 7.0 11.0 25.0 NY- 4 0.5 5.0 10.0 13.0 25.0 NY - 5 0.5 3.5 6.0 12.0 24.0 NY- 6 1.0 4.5 7.0 13.0 26.5 NY- 7 1.0 3.5 7.0 14.0 28.5 NY - 8 1.0 5.5 11.5 17.5 30.0 NY- 9 0.5 1.5 3.5 5.5 7.0 12.5 24.0 NY - 10 0.1 2.5 4.5 6.0 10.5 14.5 23.0 NY - 11 0.1 5.0 8.0 12.0 18.0 29.0 NY- 12 0.1 6.0 10.0 15.0 NY- 13 0.1 3.0 5.0 9.5 13.0

MEAN 0.5 3.9 7.0 11.3 19.8 20.4 23.5

Standard Deviation 0.37 1.29 2.37 3.41 7.67 6.79 0.71

Radial Force 0.0 0.31 l.J2 2.71 6.33 8.16 11.28 (xl05 dy:ges per CM.~)

Controle for Pantothenic Acid-deficient and Magnesium deficient rats Mean weight at the time of the experiment - 75 grams. - 109 -

TABLE XI

EFFECT OF INTRALUMINAL PRESSURE (in millimeters of mercury) WITH DISTENSION BY FLUID OF STOMACHS FROM MAGNESIUM-DEFICIENT RATS

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc

lVI - 1 2.0 5.5 7.5 13.0 15.0 20.0 35.0 M- 2 3.0 7.5 11.0 20.0 M- 3 0.5 4.5 7.0 9.5 13.0 23.0 34.5 42.5 M- 4 2.0 8.0 12.0 14.0 19.0 29.0 34.0 M- 5 1.0 5.0 9.5 13.5 24.0 39.0 M - 6 1.0 3.0 6.5 g.o 11.5 14.0 27.0 40.0 M- 7 1.0 5.5 9.5 17.5 34.5 54.5 !1 - 8 1.5 6.0 10.5 13.0 17.5 22.5 29.0 M- 9 1.5 5.5 9.o 13.0 16.5 22.0 32.0 41.0 N - 10 1.5 6.0 8.5 11.5 13.0 17.0 25.0 30.0 39.0 M - 11 1.0 5.5 8.5 10.0 13.0 16.0 25.0 H - 12 0.5 2.5 5.5 6.5 g.o 13.0 17.5 26.0 }1 - 13 0.5 10.5 26.0 35.0 M - 14 2.0 8.0 11.0 13.0 17.0 25.0 36.0 48.0 M - 15 1.0 7.0 g.o 11.0 15.0 19.0 29.0 37.0

MEAN 1.3 6.0 10.1 13.9 16.8 24.2 29.5 37.8 39.0

Standard Deviation 0.70 2.02 4.76 6.69 6.03 10.57 5.61 7.55

Radial Force o.o 0.48 1.62 3.33 5.38 9.68 14.16 21.17 24.96 (xl05 dy~es per cm. )

Mean weight at twenty one days of age - 46.5 grams Mean weight at the time of experiment - 90.5 grams Mean age at the time of experiment - 59.0 days - llO - TABLE XII

EFFECT OF INTRALUMINAL PRESSURE (in millimeters of mercury) WITH DISTENSION BY FLUID OF STOMACHS FROM PANTOTHENIC ACID-DEFICIENT RATS

Experirnent Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc PA - 1 1.0 7.5 12.0 22.0 46.0 66.0 PA - 2 o.o 8.0 14.0 29.0 PA - 3 1.5 7.5 12.0 27.0 59.0 PA - 4 1.0 6.0 9.0 14.0 23.0 36.0 54.0 PA - 5 0.5 6.0 10.5 20.0 38.0 PA - 6 4.5 9.0 13.0 16.0 25.0 58.0 PA - 7 1.0 7.0 PA - 8 4.5 10.5 19.0 49.0 PA - 9 0.5 10.0 22.5 52.0 PA - 10 2.0 11.0 20.5 45.0 PA - 11 2.0 8.5 12.0 25.0 PA - 12 3.5 10.5 14.0 17.5 32.0 52.0 PA - 13 1.0 7.0 10.5 22.0 37.0

MEAN 1.8 8.3 14.1 28.2 37.1 53.0 54.0

Standard Deviation 1.49 1.72 4.28 13.15 12.46 12.70

Radial Fo5ce 0.0 6.64 2.26 6.77 11.87 21.20 25.91 (x10 dy~es per cm. )

Mean weight at twenty one days of age - 42.0 grams Mean weight at the time of experiment - 65.0 grams Mean age at the time of experiment - 59.4 days - lll -

The initial pressure recorded in the control group of rats prior to rupture was 23.8 millimeters of mercury; the radial and longitudinal forces aver aged 8.55 x 105 and 2.14 x 105 dynes/cm.2 respectively. In the animals which have been kept for four preceding weeks on a magnesium-deficient diet, the mean intraluminal pressure at the bursting point was 32.5 millimeters of mercury and approximately thirty per cent higher than in control rats. The mean radial and longitudinal forces were calculated at 18 x 105 and 4.56 x 105 dynes/cm. 2 respectively. In rats kept on pantothenic acid-deficient diet for four to six weeks period, the intraluminal pres sure at the point of rupture averaged 43.6 millimeters of mercury and therefore approximately one hundred per cent higher than in the control animals. The radial and longitudinal forces recorded at this time (14.38 x 105 and 3.60 x 105 dynes/c~. 2 respectively) exceeded considerably the values observed in the con trol animals (8.55 x 105 and 2.14 x 105 dynes/cm. 2 respecti vely). In another group of rats it was attempted to potentiate the effect of pantothenic acid-deficiency - 112 -

TABLE XIII

EFFECT OF INTRALUMINAL PRESSURE (in mi11imeters of mercury)

WITH DIST~NSION BY F~UID OF STOHACHS FROM NORI"IAL YOUNG RATS THAT HAVE BEEN TRAUNATIZED WITH 400 REVOLUTIONS OF THE NOBLE-COLLIP DRUM

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc NYT- 1 0.1 3.5 5.0 6.0 9.5 19.0 26.0 NYT- 2 0.5 3.5 6.0 7.0 9.5 14.0 18.0 28.0 NYT- 3 0.1 2.0 3.0 5.0 9.5 15.0 NYT - 4 0.5 4.5 6.0 8.0 10.0 14.0 19.0 27.0 NYT- 5 0.5 4.0 6.0 8.0 9.5 14.0 23.0 NYT- 6 0.2 5.5 9.5 19.5 1'YT- 7 0.1 5.5 g.o 14.0 NYT- 8 2.0 7.0 10.0 14.0 1'YT- 9 0.5 4.5 7.0 9.5 17.0 25 .o NYT - 10 0.2 4.5 8.0 15.5 27.0 1TYT - 11 0.2 4.5 7.0 8.5 9.0 10.5 12.0 17.5 NYT - 12 0.1 4.5 7.0 8.5 10.0 14.0 22.0 30.0 NYT - 13 0.5 4.0 5.5 8.0 12.5 18.0 23.0 33.0 liTT - 14 0.2 3.5 8.5 12.5 22.0

IYŒAN 0.4 4.4 6.9 10.3 13.2 15.9 20.4 27.1

Standard Deviation 0.49 1.17 1.92 4.15 6.13 4.20 4.58 5.84

Radial For5e o.o 0.35 1.10 2.47 4.22 6.36 9.79 15.18 (x10 dynes per cm.2)

Contro1s for Pantothenic Acid-deficient and :t-iagnesium defi.cient rats Mean weight at the time of the experirnent - 75 grams. - 113 -

TABLE XIV

EFFECTS OF INTRALUMINAL PRESSURE (in millimeters of mercury) WITH DISTENSION BY FLUID OF STOMACHS FROM PANTOTHENIC ACID-DEFICIENT RATS THAT HAVE BEEN TRAUMATIZED WITH 400 REVOLUTIONS ON THE NOBLE-COLLIP

DRUI\'1

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc PAT- 1 o.o 7.0 10.0 18.0 24.0 PAT- 2 3.5 8.0 9.0 13.0 26.0 PAT- 3 1.5 4.5 s.o 22.0 42.0 PAT- 4 1.0 3.5 7.5 9.5 16.0 27.0 34.0 PAT- 5 o.o 5.0 9.0 16.5 36.0 PAT- 6 1.0 7.0 8.0 10.0 13.0 29.0 34.0

MEAN 1.2 5.8 8.6 14.8 26.2 28.0 34.0

Standard 1.26 1.75 1.98 4.89 11.21 1.41 Deviation

Radial Forge o.o 0.46 1.38 3.55 8.38 11.20 16.31 (xlO dynes per cm.2)

Nean weight at twenty one days of age - 45 grams Mean weight at the time of experiment - 75 grams Mean age at the time of experiment - 66 days. - 114 -

by subjecting the animals to Noble-Collip drum ming, prior to the experimental preparation. The bursting point pressure recorded in these animals was 35.3 millimeters of mercury and the radial and longitudinal forces were 12.27 x 105 and 3.07 x 105 dynes/cm. 2 respectively. It appears therefore that the application of Noble-Collip drumming resulted in a decrease rather than the expected increase of the bursting point. Whether this was due to the development of a certain degree of "paralytic" resis tance, it cannet be stated with certainty. It is interesting to note that all of the animals of this group developped gastric dilatation after being sub jected to the Noble-Collip drumming, while in none of the rats within the same weight range subjected to Noble-Collip drumming alone, gastric dilat~tion could Df' o bserved: in this las t group the bursting point pressure was 16.7 millimeters of mercury and radial and longitudinal forces of 10.18 x 105 and 2.56 x 105 dynes/cm. 2 respectively. It can be concluded from the data presented above that both magnesium-deficient and pantothenic acid-dificiency result in distension and loss of 1-'

1-'

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p.. :::::> Cl)

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- 0 :::::> ~ f-'• li r-o ct f-'· ~ p.. :::s ~

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'<:

Gtl

0 0

0 0 0

0 0

() 0

0 0 0

0 0

0 0 0

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C\J - 116 - FIGURE XXI

(Rats weighing 70 80 gra.ms)

7 •105.

25•10'

~-JO ' ~ ::::s ...... --. oq 20•to' C\l SdO !-1• • 1 c+s;:; 1 (.)a p., 1 J-4 ...... 1 ::::s Ol 1 y s::Q) 1 1 '·10· ~ 15•10' BI J31 1 1 ~ 1 1 ~ 1 li -Q) 1 0 (.) 1 l -10' (1) 1 H 1

0 i0 11 10s 1 P-:l 1 ~- T/ ,-; / l•iD' ; m 1 •ri rd ~ ~ S .. id. ~ 1,. f0 5 • N

; / / -

J2 !. j6

Volume (Ivlillili ters) EFFECTS OF DISTENSION UPON THE STOMACH WALL OF VARIOUS EXPERIMENTAL ANIMALS

Legend

1 A Normal rats A - Normal rats traumatized by Noble-Collip drumming B Pantothenic acid ' deficient Jrats B' - Pantothenic acid-deficient rats traumatized by Noble c Magnesium-deficient Collip drumming rats - 117 -

tone of the gastric wall. The increase in burst ing point pressure values is more pronounced in animals kept on magnesium-deficient diet than those in which pantothenic acid was lacking. Thus, the clinical use of enzymes preparations which con tain pantothenic acid in patients with gastric dilatation appears to be justified. Although the effect is probably not as pronounced as it is fre quently claimed. The above results indicate also that the administration of magnesium preparations might have an even more beneficial effect than those of pantothenic acid. I•1agnesium-deficiency is rare in Man, but occasionally occurs as a result of massive intes tinal resection or in conditions where we have inadequate food intake simultaneously with the excessive loss of fluids. The clinical syndrome presents as a tetany, and is diagnosed by a low serum magnesium and a good response to treatment with magnesium sulphate (Fletcher, 1960). - 118 -

c. Effects of Distension on the Wall of the Ruminee- tomized Stomach. As discussed in Chapter Vll, the rationale behind ruminectomy was to convert the rat 1 s stomach into a glandular one so as to simulate the human organ. Eighteen rats were used to establish this group. As compared to the group of normal animals, a much smal ler volume was necessary to produce a much greater intraluminal pressure, that is 88 mi1limeters of mercury at the point of rupture. However the radial and longitudinal forces, being functions of the volume and the pressure were found to have mean values of 32.24 x 105 and 8.06 x 105 dynesjcm. 2 respectively, or equal to approximately sixty five per cent of the normal values at the point of rupture. It can be concluded from the above data that the forestomach has a much higher capacity for disten sion than the glandular stomach. Considerable difficulty was encountered in the group of previously ruminectomized rats that had their stomachs distended with fluid for twenty-four hours, as seventy five per cent of the experimental animals did not survive this procedure. lt was found - 119 -

FIGURE XXII

Post-mortem specimen of rat four weeks following vagotomy. The stomach is distended with gas and f1uid. - 120 -

TABLE Tf

EF:F'ECT OF INTRALUMINAL PRESSURE ( i.n mi11imeters of mercury) WITH DISTENSION OF GLANDULAR STOMACHS (in which the forestomach has been resected) OF RATS BY FLUID

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14- cc 16 cc G- 1 1.5 7.0 15.0 23.5 45.0 86.0 95.0 G - 2 5.0 10.0 17.0 29.0 54.0 100.0 125.0 ~ G- / 1.5 7.0 14.0 21.5 41.5 79.0 97.0 G- 4 1.0 8.5 20.0 28.5 53.0 85.0 G- 5 1.5 6.0 14.0 23.0 69.0 89.0 G- 6 1.5 a.o 19.0 34.0 72.0 G - 7 1.0 7.0 13.0 24.0 54.0 82.0 G - 8 1.0 e.o 15.0 18.0 43.0 97.0 G- 9 2.0 9.5 26.0 72.0 124.0 G - 10 2.0 9.5 19.0 41.5 81.0 G - 11 1.0 9.0 15.0 33.5 74.0 G - 12 1.5 9.0 21.5 69.0 100.0 G - 13 3.0 9.0 20.0 57 .o 94.0 G - 14 0.5 7.0 15.0 52.0 83.0 G - 15 1.0 9.5 31.0 83.0 G - 16 1.0 10.5 22.0 43.0 G- 17 0.5 8.0 20.0 55.5 77.5 G - 18 2.5 10.0 20.0 40.0 73.0

MEAN 1.6 8.4 18.7 41.6 71.1 88.3 105.6

Standard Deviation 1.06 1.29 4.60 19.30 22.68 7.69 16.77

Radial Forge o.o 0.67 2.99 9.99 22.75 35.31 50.69 (xlO dynes per cm .2) - 121 - TABLE XVI

EFFECT OF INTRALUMINAL PRESSURE (in millimeters of mercury) WITH DISTENSION BY FLUID OF GLANDULAR STOMACHS (in which the forestomach has been resected) FROM RATS THAT HAVE BEEN SUBJECTED TO MECHANICAL DILATATION FOR TWENTY-FOUR HOURS

Experiment Volume Injected Number 0 cc 2 cc 4 cc 6 cc 8 cc 10 cc 12 cc 14 cc 16 cc DG - l 5.0 7.5 8.0 9.5 13.0 32.0 68.0 DG - 2 2.0 6.5 9.5 14.5 37.0 87.0 DG - 3 3.5 6.5 12.0 22.0 75.0 95.0 DG- 4 3.0 4.5 9.0 42.0 96.0 DG - 5 0.5 6.0 10.5 22.0 57.5 98 . 5 DG - 6 4.0 4.5 8.0 28.5 66.5 DG- 7 2.5 4.5 5.0 6.0 7.5 17.0 DG - 8 o.o 5.0 6.0 10.0 20.0 53.0 67.0 105.0 DG- 9 2.0 4.5 5.5 7.0 9.0 20.0 46.0 83.0 DG - 10 1.5 4.5 7.0 12.0 17.0 40.0 94.0 DG - 11 1.5 6.5 12.0 26.0 90.0 DG- 12 4.0 5.0 6.0 7.0 11.5 27.0 50.0 85.0 DG- 13 0.5 6.5 13.0 26.0 56.0 90.0 DG - 14 1.0 9.0 16.0 27.0 38.0 DG - 15 0.5 6 . 5 12. 0 20 . 0 29.0 DG- 16 1.0 4.0 5. 5 7 . 0 9.0 19.0 47.0 80.0 DG- 17 2.0 8.0 17.0 38.0 65.0 85.0

2.0 5.8 9.5 19.1 41 .0 53.3 62.0 88.3

Standard Deviation 1.45 1.44 3.69 11.19 29.91 33.23 18.49 11.35

Radial Forge o.o 0.45 1.52 4.58 13.11 22.12 29.76 49.44 (x10 dy~es per cm. ) - 122 -

FIGURE XXIII

Rumincctoa:y Ru:ninecto::Jy pl us Die tension

5 16 x 10 ,-... 30 x 105 C\1 • t-i s 0 0 ~ """- ~ Ul 1-'· s::Q) c+ 12 x 105 p.>:: ~ 1-'· ~ -Q) 0 20 x 105 ~ J.t 0 t:J;j p:. 0 ti 5 0 trl 8 x 10 (t) ·ri ,-... rC p. <.:! ~ ~ (t) 5 {Il 10 x 10 """- 0a 4 x 105 • ..._...1\)

COMPARISON OF BURSTING POINTS OF STOMACHS OF THE VARIOUS EXPERIMENTAL ANIMALS - 123 -

that these stomachs, after being dilated with fluid for twenty-four hours were quite toneless.

~~e initial pressure (two millimeters of mercury), before the injection of fluid, was greater than that recorded in simple ruminectomized stomachs (1.6 millimeters of mercury). This discrepancy could not be accounted for as well. Just prior to rupture, the mean pressure recorded was 76.9 millimeters of mercury as compared to 88 millimeters of mercury in undistended glandular stomachs. The radial and longi tudinal forces of 33.21 x 105 and 8.3 x 105 dynes/cm. 2 respectively, which only slightly exceeded the figure in its undistended counterpart (32.24 x 105 and 8.06 x 105 dynes/cm. 2 respectivel~. - 124 -

TABLE XVII

INTRALUMINAL PRESSURE AND RADIAL AND LONGITUDINAL FORCES

AT WHICH STOMACHS OF VARIOUS EXPERIMENTAL ANI~~LS RUPTURE

Pressure Radial Standard Longitudinal mm. Hg Force * Deviation Force * Normal 42.3 50.95 30.30 12.74 Vagotomized 65.3 74.67 59.67 18.67 Traumatized 78.6 86.26 33.47 21.56 Ruminectomized es.o 32.24 11.45 8.06 Distended Ruminectomized 76.8 33.21 14.50 8.30 Normal Young 23.8 8.55 2.45 2.14 11agnesium - Deficient 36.9 18.24 6.94 4.56 Pantothenic Acid-Deficient 46.9 14.38 8.00 3.59 Normal Young Traumatized 16.7 10.18 5.01 2.54 Pantothenic Acid - Deficient 35.3 12.27 3.78 3.07 Traumatized

5 * Values of Force are measured in x 10 dynes/cm. 2 - 125 -

CHAPTkR X SUMMARY AND CONCLUSIONS

l. The etio~ogy and the course of gastric dilatation has been presented including a description of the symptoms and signs, the laboratory findings and the treatment of the condition. The prophylactic measures undertaken in cases of acute gastric dilatation have been discussed.

L. The pathological findings in acute gastric dila tation, including those o! spontaneous rupture of the stomach, have been described. j. The subject of gastric dilatat1on in animals has been reviewed and an attempt has been made to correlate the findings with human subjects. 4. A method for the study of the effects of acetylcholine on strips of the glandular portion of the gastric wall has been developped and the effects of various concentrations of the compound upon the contractility of the stomach wall has been studied. The following conclusions are drawn: a. Only strips of normal stomachs respond to con centrations of acetylcholine as law as 10-7. - 126 -

b. Strips of stomach taken from vagotomized rats are on the whole more sensitive at the higher concentrations of acetylcholine, namely 10-5 to 10-3 • c. Gastric strips taken from ruminectomized rats are less sensitive to all concentrations of acetylcholine. d. Strips taken from ruminectomized rats that have been subjected to distension with fluid for twenty four hours exhibited tne least amplitude of contraction to all concentrations of acetyl choline. e. Stomachs from rats subjected to ischemie trauma reacted irregularly in that a concentration of 10-5 acetylcholine produced a maximum contraction, whereas the response to 10-3 and 10-4 concentrations of acetylcholine progressively dimi- nished in amplitude. f. Distended rruninectomized stomachs from vagotomized rats responded in a manner between that of specimens taken from simple rruninectomized stomachs and stomachs of vagotomized rats. However, the response obtained from a concen- - 127 -

tration of acetylcholine of lo-3 was less in amplitude to that obtained by the administration of 10-4 • 5. A method of measurement of the intraluminal pressure, radial and longitudinal forces exerted upon the gastric wall, by distending the stomach of rats has been devised and the preparations studied under various experimental conditions. These include the effects of vagotomy, ruminectomy, mechanical dis tension of the stomach with fluid, traumatic shock and pantothenic acid and magnesium deficiency. It is concluded that: a. Vagotomy causes the stomach to lose some of its tone and motility, and a much greater volume of distending fluid was necessary to obtain values of intraluminal pressures and forces comparable to those stomachs of normal rats. b. Traumatic shock produces a stress reaction in which inadequate amounts of acetylcholine is synthesized to maintain good gastric tone and motility. The stomach is therefore flabby as compared to that of the normal rat, and greater intraluminal pressures are required to cause - 128 -

the gastric wall to rupture. o. Pantothenic acid and magnesium are essential constituants for the normal growth and develop ment of rats. Deficiencl.es in these substances result in the general stunting of the growth of the animals with contraction of the gastro intestinal tract and the absence or decrease in gastric tone and motility. Subsequently, a lesser intraluminal force was necessary to cause the rupture of the gastric wall. - 129 -

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