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 re- spiratory 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 experi- ments, 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 re- spiratory 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 respira- tory 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 tempo- rarily acceleration of respiratory rhythm. When the level of transection moves more caudally (5 in fig. 1), the ampli- tude 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 respira- tory 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 pro- duces 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 pro- longed respirationsdiffer in theirnature from Lumsden's "apneusis." Therefore it seems to us that the expression "apneustic breathing,"to denote the pro- longed 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 re- spiration(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.