Helen C. Coombs

The rôle of afferent impulses in the control of respiratory movements

As the result of further experimentation, we wish to add to a previous statement (American Journal of Physiology, 1917, XLII, p. 395) the following facts: 1. The movements of the ribs, which cease after division of the dorsal roots of the spinal nerves in the thoracic and cervical regions, are resumed when the phrenics are divided. 2. The respiratory movements become labored when the vagi are divided in the neck after these procedures, and soon cease. The effects of vagotomy are more severe if the dorsal roots of the cervical nerves have been included in the section than if the thoracic nerves alone are affected. 3. The results of combined section of the dorsal roots of the spinal nerves and the vagi are similar to the effects of combined section of the brain stem below the corpora quadrigemina and the vagi. Transection below the corpora quadrigemina adds little or not at all to the severity of the effects following section of the dorsal roots. 4. Costal respiratory movements are resumed after section of dorsal roots, brain stem below the corpora quadrigemina and phrenics if the vagi are intact. We believe that these experiments bring the intercostal muscles into line with the other skeletal muscles so far as the functional relations of afferent to efferent spinal nerve roots are concerned. 1 We believe also that the experiments show that it is necessary that afferent impulses shall not merely have access to the central system, but that they shall go to a particular part of the central system in order to fulfill their function. In the case of the respiratory movements, afferent impulses from the intercostal muscles must go as far up as the corpora quadrigemina. The medulla oblongata seems sufficient for the establishment of any necessary connection of the vagi with efferent paths to the respiratory muscles.

Effect of Division of Dorsal Roots of Cervical Nerves Upon Diaphragmatic Respiratory Movements

In a study of the neuro-muscular mechanism of respiration, carried out on cats, it has been observed that, in many cases, division of the vagi is followed not only by a marked decrease of the respiratory rate, but also by a diminution in amplitude of diaphragmatic movements, while costal movements increase in depth. Subsequent section of the dorsal cervical (phrenic) nerve roots in these cats is attended by very little further change in respiratory rate or movement. When, on reversing the order of experimental procedure, the dorsal roots of the cervical nerves (iii, iv, v, vi) are divided first, both a diminution in amplitude of diaphragmatic contractions and slowing in rate ensues, and subsequent division of the vagi brings about almost no further change in respiratory rate. That respiratory impulses to the diaphragm may still bring about increased depth of diaphragmatic movement after section of the dorsal roots of the cervicals, has been shown by division of the dorsal spinal nerve roots of the intercostals in the thoracic region with the resulting diminution in costal movement. Under such conditions, there is an increase in the magnitude of diaphragmatic movement. This is similar to the increase in costal movements observed by us some years ago when, after division of the dorsal spinal nerve roots in the thoracic region, the phrenics were excised and an increase in the magnitude of costal movement was observed. 1 The fact that diaphragmatic movement and not costal, is- diminished in magnitude by division of the vagi, appears to indicate a closer relationship of the vagi to the phrenics than to the thoracic roots of the nerves concerned in the control of costal respiratory movements. These latter appear to have central stations as high as the posterior corpora quadrigemina, section behind which affects costal respiratory movement to a much greater extent than diaphragmatic. 2

The effect of varying pressures upon the abdominal musculature in the cat

Sherrington 1 has summarized rather completely our knowledge of tonus for smooth and striated muscle. He believes that muscle fiber is not to be considered as an elastic string, for it has the property of exhibiting different lengths with one and the same degree of tension. This doctrine is of special interest in the case of the abdominal musculature, which is of necessity subject to many changes in pressure due to the many variations which occur in the abdominal contents. We should therefore expect to find the muscle fibers of the abdomen showing different lengths with the same degree of tension, or, to put it conversely, to exhibit a fairly constant pressure with varying increments of volume. The object of these experiments has been to determine whether this regulation of inter-abdominal pressure is essentially a function of the nervous mechanism of the abdominal walls or of the intrinsic musculature itself. Cats were used in these experiments under the several conditions of light and deep anesthesia and decerebration. A cannula introduced into the abdominal cavity was connected by a 3-way stopcock with a manometer and a burette filled with 0.9 per cent. sodium chloride solution kept at a temperature of 38 degrees centigrade. Costal respiration was recorded throughout the experiment. The warmed saline was admitted to the abdominal cavity at the rate of 10 C.C. a minute. With each increment of fluid the pressure was read from the manometer and plotted against the volume. A curve was thus obtained for the entire experiment, which, in about fifty cases was found to be typical. There was a slow increase of pressure in proportion to volume until a certain point was reached, from which pressure rose much more rapidly.

Arrest of Experimental Convulsions by Acetylcholine in the Cat.

Following a control series of experiments (15 cats) in which (1) the minimal convulsive dose of camphor monobromide, 1 (2) the total number of such dosages, (3) the total number of convulsions which could be elicited before the animal succumbed, and (4) the total amount of the drug which could be intravenously administered with 15-minute intervals between the dosages, had been established, a series of 25 cats was studied in which after establishing the minimal convulsive dose of camphor monobromide, varying dosages of acetylcholine (anhydrous solution, Chevretin-Lematte) ranging from 1:1 × 10−7 to 1:1 × 10−3 gm. per kilo weight were injected intravenously just before the administration of the camphor monobromide, to determine how, if at all, the convulsions would be affected. Results. It was found: 1. That a concentration of 1 × 10−6 gm./kg. was the smallest dose of acetylcholine which would arrest the clonic convulsion following a minimal dose of camphor monobromide. 2. That while the first dosage at such a concentration would arrest clonic convulsions, a repetition of the same dosage after an interval of 15 to 30 minutes would only delay the onset of the clonic convulsions, for an interval of from 30 seconds to 10 minutes, and it was necessary to employ a greater concentration of acetylcholine before a complete arrest of clonic convulsions was again obtained. 3. A concentration of acetylcholine of 1 × 10−4 to 1 × 10−3 gm./kg. would always arrest a convulsion, sometimes proving lethal. (We have found the control lethal dose of this preparation of acetylcholine in the cat ranges between 0.01 and 0.09 gm./kg. 2 ) 4. While acetylcholine blocks the clonic element in such convulsions, it does not affect the element of tonic extension. 3

A Comparison of Effects of Stimulation of Right and Left Peripheral Vagus with Action of Acetylcholine on Electrocardiogram of the Cat

Electrocardiograms were taken in a series of experiments on 40 cats, in which nembutal was the anesthetic employed. The procedures were as follows: 1 Stimulation of the right and left peripheral vagus only; (20 cats.) 2 Jugular injection of acetylcholine (2 to 6 mg./kg.). (20 cats.) Typical electrocardiograms illustrate the following results: 1 Stimulation of the right vagus brings about a decrease in the rate of both P and QRS complexes, i. e., a sinus bradycardia. 2 Stimulation of the left vagus brings about the dropping out of some QRS complexes, i. e., a partial block. 3 Acetylcholine brings about (a) a decrease or temporary cessation. of QRS Complexes; (b) a heavier dosage (sublethal, about 6 mg./kg.) may result in temporary elimination of P-waves also. Dale 1 has stated that “vagus impulses produce their effect by liberating acetylcholine among the fibers of the muscular wall of the heart.” From these results it would seem that the action of acetylcholine on the heart more closely approximates that of the left, than of the right, vagus. The question is, therefore, raised as to whether some vagus fibers to the heart may not be more “cholinergic” than others, and a further differentiation of their activity on such a basis ultimately attempted.

Contracture of the Rectus Abdominis, Tetany, Calcium and Phosphorus, after Spinal Transection, with and without Thyro-parathyroidectomy

As one phase of some observations on the effects of parathyroidectomy on cats, 1 a previous study 2 showed that on stimulation of the rectus abdominis muscle following thyroparathyroidectomy, more contracture usually appeared than was the case with the same muscle stimulated in the same manner in control animals. During the past months a series of experiments has been done on 20 cats in which the ionizable calcium and inorganic phosphorus of the blood were determined from 2 to 3 days after (1) aseptic transection of the spinal cord alone in the upper thoracic region and (2) when thyroparathyroidectomy was done at the same time as the spinal transection. The working power of the curarized muscle, together with the presence or absence of tetany and of contracture, was determined in the same manner as in previous experiments. The results are given in Table I. It appears from the table that 1. Either contracture or tetany was present in all but one case, in which the contracture occurred at the beginning of the excitation of the muscle and was merely transitory. 2. Contracture and tetany were found together in only 6 of the 20 experiments. There appears to be no necessary relationship between them. 3. Contracture did not occur when the ratio of calcium to phosphorus was less than one, except in one case (No. 9). From these and previous observations it would appear that contracture occurs infrequently when the ratio of calcium to phosphorus is less than one, and then only when the calcium is relatively low; on the other hand, contracture was observed in only one case where the concentration of phosphorus was above 8 mg. per 100 cc. serum. (No. 6.)

Combined Effects of Drugs and Electrical Excitation of Cortical Motor Area in Cats.

It was shown that, following the method of Frangois-Franck, 1 between 35 and 55 clonic convulsions could be elicited in cats by stimulating the cortical motor area with the induced tetanizing current before the animals succumbed. 2 Wortis, Coombs and Pike 3 observed that from about 5 to 10 clonic convulsions can be induced by the administration of convulsant drugs such as camphor mono-bromide before respiration fails and blood pressure falls to base line. 4 In this series, which first developed as a set of controls in another group of experiments, I wished to see whether a combination of both methods would be more or less effective in prolonging or curtailing the number of convulsions and the resistance of the animal, than the use of one method alone. Two methods of procedure were carried out. 1. In a series of 10 cats, the motor area was exposed under ether, and the anesthetic then intermitted. After recovery from ether, the cortex was stimulated with a mild induced tetanizing current as previously described. When the cortex had been stimulated from 25 to 40 times, with the usual clonic convulsions, a dose of camphor monobromide which corresponded to about the estimated minimal convulsive dose for the weight of the animal, was injected intravenously. In most cases, it proved fatal. Respiration failed and the animal usually died in tonic extension without the usual typical clonic convulsion, or with only a few clonic twitches. 2. In another series of 12 cats, after exposure of the motor area under anesthesia, with one electrical excitation to make sure the clonic convulsive response was readily elicitable, the estimated minimal convulsive dose of camphor monobromide or absinth was administered.

Effect on Costal Respiratory Movements of Division of the Phrenics Following Transection of the Midbrain.

It has been shown that section of the dorsal roots of the thoracic nerves is followed by cessation of costal respiratory movements which are promptly resumed if the phrenics are excised, the vagi and midbrain being intact. 1 (The effect of section of the dorsal roots is somewhat greater when the cervical as well as the thoracic roots are sectioned. 2 ) Section of the midbrain alone at the level of the inferior colliculi is followed by a diminution of costal movements and the rate of respiration is somewhat slowed, but remains regular. The question arises therefore whether section of the phrenics would have the same effect on costal respiration after section of the midbrain as after section of the dorsal roots of the thoracic nerves. The observed effects of division of the phrenics subsequent to transection of the midbrain in 30 cats are: 1. An increase in the depth of the costal respiratory movements, which is to be expected. 2. The respiratory rhythm immediately becomes irregular. There may be pauses of 5 to 10 seconds followed by from 5 to 10 costal movements and a succeeding pause. In some cases the tendency to grouping is slight. The character of the individual movements may vary. Sometimes there may be a rapid abrupt inspiratory movement followed without pause by an equally abrupt expiratory movement with a rhythm of 10 to 12 a minute. A series of from one to 3 small inspiratory movements may precede the actual large abrupt inspiration. When the group character is more pronounced, the inspiration is not so abrupt and expiration follows after a more appreciable interval. So long as the vagi are intact, section of the dorsal roots of the phrenics, following transection of the midbrain does not elicit irregular respiration.

The rôle of the accelerator nerves in bulbar anemia.

In a previous report 1 on the action of the vagus in bulbar anaemia induced by temporary occlusion of the head arteries, it was shown that, after division of both vagi, the heart rate does not change during the anaemic rise of blood-pressure, but remains at whatever maximum rate was attained after vagotomy. It has been thought desirable to find out the effect on heart rate during the cardio-vascular response to bulbar anaemia, of removal of the stellate ganglia through which run the accelerator fibers to the heart. Accordingly, in a series of cats, after a control occlusion had been done according to the usual method, 2 the stellate ganglia were excised and further occlusions were done. Following is a typical result of such an experiment. It is evident from the above table, that, with the accelerators eliminated, the vagi are over-active in holding the heart rate down. Under such conditions, recovery of the medulla after the circulation has been restored to the head arteries may, at times, be somewhat difficult, owing to the combination of low blood-pressure and slow heart rate. Moreover, this activity of the vagus is in evidence at a time when blood-pressure is at spinal level and all other signs of bulbar activity are in abeyance. In the experiment which has been given above, the vagi were sectioned in the recovery period, and heart rate increased immediately from 94, at which it had been for about five minutes, to 156; while blood-pressure rose from 40 to 70 millimeters of mercury. With both vagi and stellates divided, the heart rate during the remaining occlusion period in the above experiment, remained between 156 and 162, which one would consider relatively constant. Whether the adrenals play any part in the maintenance of heart rate in the denervated heart under conditions of bulbar anaemia, is, at present, under investigation.

Observations on the relation of the adrenal glands to the blood-pressure response during cerebral anæmia in cats and rabbits:

The blood-pressure response during cerebral anæmia was analyzed by Pike, Guthrie and Stewart a number of years ago. Recently Winkin in studying some of the nervous factors involved in the cardio-vascular changes which take place during cerebral anæmia observed that after repeated occlusions of the head arteries for short periods, the curve of the anæmic rise may become dissociated into two distinct parts. The question was raised by Winkin whether the second part of this anæmic rise may not be due to increased availability of some product of adrenal activity which the “cardio-vascular relations found in the mammalian organism under extreme conditions of stress” would call forth. With this in mind, we have carried out a series of experiments on cats and rabbits when: 1. The adrenal glands are tied off, or excised during an acute experiment. 2. The adrenal veins are clipped. 3. The remaining adrenal is excised (one having been previously excised and the animal allowed to recover). 4. One adrenal is excised and the other denervated (and the medulla of it curetted out or a large part of the remaining gland excised in addition to denervation) and the animal allowed to recover. 5.: Both adrenals are excised (rabbit) and the animal allowed to recover. In cases 3, 4, and 5 the animals were operated upon from two to four weeks before the acute experiments were performed. The technique of the acute experiment was that devised by Stewart, Guthrie, and Pike in which the arteries are secured as they emerge from the thorax. It is well known that in the cat and rabbit, when the carotid and subclavian arteries (proximal to the origin of the vertebrals) are occluded, circulation to the head is completely interfered with and cerebral anaemia with the attendant anxmic rise of Mood-pressure ensues rapidly.