Vail Two Concepts

ON THE LOCALIZATION OF THE RESPIRATORY CENTER

TAKESI HUKUHARA, SOSOGU NAKAYAMA, SABURO BABA AND TADASI ODANAKA * Department of Physiology, Faculty of Medicine, Tottori University

Regarding the function and localizationof the respiratorycenter there pre- vail two concepts. According to one the respiratorycenter has inherentlyno rhythmicity,the appearance of which is dependent upon the afferentimpulses reaching the center through the vagi from the lung receptors as well as through the brain stem from the region of the pons. Lumsden (1) localizesthe center in the lower pontine region i.e. in the striaeacusticae, while Pitts and his co- workers (2) localizeit in the medulla. According to the second theory the respiratory center discharges the impulses autochthonously rhythmically to the respiratorymuscles. Recently Hoff and Breckenridge (3, 4) insistthat such periodicimpulses have their origin in the medulla oblongata. Here we report the resultsof our investigation,because our concept derived from our experiments, does not agree with any of the above mentioned theories.

METHOD

As in the previous experiments (5, 6) a record of the movement of a dorsal slip of the diaphragm serves as an index to the rhythm and extent of the respiratory movements. In the experiments rabbits, cats and dogs were used. To the rabbit 1g. of urethane per kilo body weight, to the cat 0.1g. of phe- nobal per kilo and to the dog 0.01g. morphine hydrochloride per kilo was ad- ministered subcutaneously. After the carotid arteries were bilaterally ligatured and the vertebral arteries temporarily occluded by digital compression at the ventral side of the neck, the skull was trephined and the portion of the brain which lies rostral to the posterior colliculus was removed by means of a metal spatula. About 30minutes after the decerebration the vagi were bilaterally severed and the cerebellum was removed. The brain stem was then transected in turn from rostral to caudal, care being taken not to injure the vertebral arteries. The room temperature was generally kept between 25℃. and 30℃. and the surface of the brain stem was covered with gauze soaked in Ringer- solution.

RESULTS Transection of the brain stem of the rabbit. The experiments were carried

Received for publication June 4, 1951. *福原武,中山沃,馬場三郎,小田中貞

44 RESPIRATORY CENTER 45

out on 20 rabbits and consistent results were obtained. The crucial levels at which severance was effected is shown in fig. 1 and the effects of severance

A B

Fig. 1. Diagram of rabbit brain stem showing the levels of the crucial sections. A: dorsal view. B: ventral view. CC: colliculus caudalis. BP: brachium pontis. TA: tu- berculum acusticae. O: obex. Py: pyramis. Line 1: level of the lower limb of colliculus caudalis. Line 2: level of the mid-pontine transection. Line 3: level of the upper limb of striae acusticae. Line 4: level of the lower limb of striae acusticae. Line 5: level of the mid-medullary transection. Line 6: level of obex.

upon the respiratory movements in fig. 2 and 3. No effect of section upon the respiration is found, when the animal is decerebrated. When the vagi are

Fig. 2. Effect of transection of rabbit brain stem on the respiratory movements . Experiment 1 (11/10/1950). Rabbit 3.6kilo body weight . Room temperature 23℃.

Time: 3sec. The tracing shows upwards the contraction and downwards the relaxation of the dorsal slip of diaphragm. The animal was previously decerebrated and both vagi

were cut. The number indicates that the section is carried out at the level of the same number shown in fig. 1. Explanation in text. severed about 30minutes later,the respiratorymovements become generally deeper and slower. The followingsection of the brain stem just behind the posteriorcolliculus (sect. 1, in fig.1) increasestemporarily the rate of respiration 46 T. HUKUHARA ET AL. which gradually returns to its original rate (1 in fig. 2).

Fig. 3. Effect of transection of rabbit brain stem on the respiratory movements. Experiment 23 (20/12/1950). Room temperature 20℃. Rabbit 2.1kilo body weight.

Time: 1cm.=9sec. The animal was previously decerebrated and vagi intact. Cr shows cramp following the transection. Explanation in text.

This tachypnea must be considered, we think, to be due to the stimulating effect produced by section. Often each accelerating respiration summates itself to produce a tetanicinspiratory contration (1 in fig.3). The sectionat this levelmay cause the decerebraterigidity interferring the tracingof the respiratory movements. Similarresults were obtainedin sectionsat differentlevels of the pons which lie between the level of the preceding section and the upper limb of the striaeacusticae: namely, the said sections(2 and 3 in fig.1) cause acceleration of respirationfollowed by gradual slowing (2 and 3 in fig.2). Section at the levelabove mentioned acceleratessometimes the respiratorymovements to make them tetanicas shown in 3 in fig.3. This form of breathing corresponds to the inspiratorycramp or apneusis which was observed by Marckwald (7) and Lumsden (1). The apneusis seems to us originallyonly an exaggerated ac- celeratingeffect of the section. We believe that the apneusis is produced by the stimulating action of the section combined with the abnormally high irrita- bilityof the pons which is caused by the experimental procedure. In the rabbit this apneusis lasts for only a short time under our experimental conditions contrary to the results obtained by the authors above mentioned. On section at the level of the striae acusticae there appears a remarkable phenomenon, i.e. on section along the caudal limb of the striae (4 in fig. 1) the breathing is changed into a breathing composed of very rapid inspiration and expiration, a breathing of Lumsden's gasping type (4 in fig. 2). At the same time the contraction of the expiratory muscles, especially the abdominal muscles, is seen and the alae of the nose as well as the openers of the mouth take part in the respiration. The section may itselfstimulate the center to cause temporarily acceleration of respiratory rhythm. When the level of transection moves more caudally (5 in fig. 1), the amplitude of respiration decreases so much (5 in fig.2), that a section at the level of the calamus scriptorius (section 6 in fig.1) abolishes completely the respiratory movements (6 in fig. 2). RESPIRATORY CENTER 47

From the resultsabove describedwe believethat an autochthonouslyactive respiratorycenter liesat the levelof the striaeacusticae, for a remarkable change in the type of breathingoccurs on sectionat thatlevel. It seems also reasonableto think that closeto thisfirst center lies the second centerwhich occupiesthe rostraltwo thirdof the medulla.The latteris awakened to send impulsesto the respiratorymuscles and to causethe gasping,when the superi- or center is extirpatedor deteriorated. Transection of the brain stem of the cat and the dog. Decerebration produces no effectupon the respirationof these animals as in the rabbit, but the sectionof the vagi has a more marked influenceon the respirationthan in the rabbit,namely a marked prolongationof the respiratorymovements is produced. The prolongation is not confined to the inspiratoryphase but also is seen in the expiratory phase and the pause, as shown in fig.4. On thispoint these prolonged respirationsdiffer in theirnature from Lumsden's "apneusis." Therefore it seems to us that the expression "apneustic breathing,"to denote the prolonged respirationproduced after section of vagi,is not adequate.

Fig. 4. Effect of transection of the cat brain stem on the respiratory mevement. Experiment 11 (6/11/1950). Cat 2.5kilo body weight. Room temperature 23℃. Time:

3sec. When the cerebellum is exposed at X, the breathing becomes deeper and slower

and a few minutes later, gasps superimpose on the prolonged respiration as shown in g. As the level of section more caudal, the more marked the gasps become and on the

contrary the prolonged type of breathing decreases in its amplitude, till it disappears en- tirely on section of the lower limb of the striae. When the cerebellum is then exposed (X in fig.4), gasps superimpose upon these prolonged respirations(g in fig.4). This may perhaps be due to some depressant effectof the procedure on the respiratorycenter. The latterbe- comes gradually limitedwhile the former predominates over the latter.At the same time the abdominal muscles contract to enhance the expirationactively. Section at any levelof the pons acceleratessuch course in the change of respiration(for example 1 in fig.4 and 3 in fig.5). If the animal is leftas it is, the gasps may become finallyonly a remaining type of breathing. When the section of pons is carried out above the striaeacusticae, before this stage is reached, a sustained inspiratory contraction,namely apneusis, is produced 48 T. FUKUHARA ET AL.

Fig. 5. Effect of transection of dog brain stem on the respiratory movement.

Experiment 33 (6/2/1951). Dog 6.5kilo body weight. Room temperature 27℃. Time: 1cm.=18sec. The animal was previously decerebrated and both vagi were cut. When the

pons is transected at the level of the upper limb of striae acusticae, a gasping type of breathing superimposes on the prolonged respiration, the amplitude of which decreases gradu-

ally, till it reaches a minimum and only a gasping seen.

frequently at the moment of section. This seems to us an exaggerated acceler-

ating effect described in experiments on rabbits. If artificial respiration is in

such cases carried out, the rhythmical respiratory movements ensue sooner or

later though they are prolonged in type of breathing.

But the apneusis is not a constant occurrence in section of the upper pons

e. g. such is not produced in an experiment shown in 2 in fig. 4. Here the

superimposed gasps predominate over the prolonged type of breathing. Section

at the caudal limb of the striae changes the respiration always into only one type of breathing, i. e. gasp (4 in fig. 4). On section of the medulla oblongata

at the level which lies above the obex the respiration is always abolished.

In cats and dogs, gasps are, during the whole course of the experiment, the

common occurence under the condition above described. The gasps are ob-

served actually on figures in the articles by the previous authors who did not

preceive this type of breathing as such. For example we can see the gasps as a short line of projectionsuperimposed on the apneusisand in the phase of rapidexpiration in figure2 in Lumsden'sarticle (1) and Hoff'sso-called "phasic contractionsof low amplitude"which are shown in figure1 in his article(4) are no other than gasps. This fact shows thatthe respiratorycenter of these animals is highlysusceptible to the influenceof cold,hemorrhage, section of the vagi and so on which are importantfactors as cause of gasping. But in- spiteof the unsatisfactoryexperiments, essentially the same resultsas in the rabbitare obtained.Thus we can concludethat the respiratorycenter can be classifiedinto two in the cat and the dog as in the rabbit,the one is located in the regionof the striaeacusticae and the other in the upper regionof the medullaoblongata. DISCUSSION As to the localizationof the firstrespiratory center our resultsaccord with that of Lumsden, but we cannot agree with his view that this center has no rhythmicity. Hoff and Breckenridge believethat the center of normal breathing is located in the medulla oblongata. But thisconclusion is deduced from the concept that the type of gasping is of the same nature with the normal type of breathing. The fact is that the gasping and the normal type of breathing can be recorded as quite a different type of breathing and that two centers which arouse these RESPIRATORY CENTER 49

two types of breathingcan also be distinguishedone from the other. The center advocated by Hoff and his co-worker seems therefore not to be a center of normal breathing but a center of gasping. From the results of stimulation experiments, Pitts,Magoun and Ranson concluded that the center islocated in the caudal two third of the medulla. According to them this center should produce only a sustained contraction,if it is separated from the pons when the vagi have been previously severed. Contrary to this theory the fact is clear that section of the upper medulla produces always a trainof abnormal type of breathing,gasps. From thisfact the so-calledpneumotaxic center as well as the vagi are, contrary to the concept of Pitts and his co-workers,not considered as essentialfactors by which the rhythmicity of respiratorymovement is maintained. From reasons above mentioned we cannot agree with any of the above mentioned theoriesin toto.

CONCLUSIONS Experiments of transecting the brain stem were made in order to determine the localization and function of the respiratory center. 1) Normal breathing changes and turns to abnormal breathing, "gasping," on section of the lower limb of the striae acusticae, while sections given rostal- ly to this region have no effect on breathing, except for transitory changes. Therefore it may be concluded that the center of normal breathing which has rhythmicity is located at the level of the striae acusticae. 2) Close to this region lies the second center which occupies the rostral two third of the medulla oblongata. This center is awakened to send the impulses to the respiratory muscles and to initiate gasping, when the superior center is deteriorated.

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