Bodily changes in pain, hunger, fear, and rage

IMPROVED CONTRACTION OF FATIGUED MUSCLE AFTER SPLANCHNIC STIMULATION OF THE ADRENAL GLAND

In the older literature on the adrenal glands the deleterious effect of their absence, or the beneficial effect of injected extracts, on the contraction of skeletal muscle was not infrequently noted. As evidence accumulated, however, tending to prove an important relation between the extract of the adrenal medulla (adrenin) and the sympathetic nervous system, the relations with the efficiency of skeletal muscle began to receive less consideration.

The muscular weakness of persons suffering from diseased adrenals (Addison’s disease) was well recognized before experimental work on the glands was begun. Experiments on rabbits were reported in 1892 by Albanese,[1] who showed that muscles which were stimulated after removal of the glands were much more exhausted than when stimulated the same length of time in the same animal before the removal. Similarly Boinet[2] reported, in 1895, that rats recently deprived of their adrenals were much more quickly exhausted in a revolving cage than were normal animals.

More direct evidence of the favorable influence of adrenal extract on skeletal muscle was brought forward by Oliver and Schäfer.[3] After injecting the extract subcutaneously into a frog they found that the excised gastrocnemius muscle registered a curve of contraction about 33 per cent higher and about 66 per cent longer than the corresponding muscle not exposed to the action of the extract. Similar prolongation of the muscle curve was observed after injecting the extract intravenously into a dog. A beneficial effect of adrenal extract on fatigued muscle, even when applied to the solution in which the isolated muscle was contracting, was claimed by Dessy and Grandis,[4] who studied the phenomenon in a salamander.[*] Further evidence leading to the same conclusion was offered in a discriminating paper by Panella.[5] He found that in cold-blooded animals the active principle of the adrenal medulla notably reënforced skeletal muscle, prolonging its ability to do work, and improving its contraction when fatigued. In warm-blooded animals the same effects were observed, but only after certain experimental procedures, such as anesthesia and section of the bulb, had changed them to a condition resembling the cold-blooded.

The foregoing evidence indicates that removal of the adrenals has a debilitating effect on muscular power, and that injection of extracts of the glands has an invigorating effect. It seemed possible, therefore, that increased secretion of the adrenal glands, whether from direct stimulation of the splanchnic nerves or as a reflex result of pain or the major emotions, might act as a dynamogenic factor in the performance of muscular work. With this possibility in mind L. B. Nice and I[6] first concerned ourselves in a research which we conducted in 1912.

The general plan of the investigation consisted primarily in observing the effect of stimulating the splanchnic nerves, isolated from the spinal cord, on the contraction of a muscle whose nerve, also isolated from the spinal cord, was rhythmically and uniformly excited with break induction shocks. When a muscle is thus stimulated it at first responds by strong contractions, but as time passes the contractions become weaker, the degree of shortening of the muscle becomes less, and in this state of lessened efficiency it may continue for a long period to do work. The tired muscle which is showing continuously and evenly its inability to respond as it did at first, is said to have reached the “fatigue level.” This level serves as an excellent basis for testing influences that may have a beneficial effect on muscular performance, for the benefit is at once manifested in greater contraction.

In the experimental arrangement which we used, only a connection through the circulating blood existed between the splanchnic region and the muscle—all nervous relations were severed. Any change in muscular ability, therefore, occurring when the splanchnic nerve is stimulated, must be due to an alteration in the quantity or quality of the blood supplied to the laboring muscle.

Cats were used for most experiments, but results obtained with cats were confirmed on rabbits and dogs. To produce anesthesia in the cats and rabbits, and at the same time to avoid the fluctuating effects of ether, urethane (2 grams per kilo body weight) was given by a stomach tube. The animals were fastened back downward, over an electric warming pad, to an animal holder. Care was taken to maintain the body temperature at its normal level throughout each experiment.

The Nerve-muscle Preparation

The muscle selected to be fatigued was usually the extensor of the right hind foot (the tibialis anticus), though at times the common extensor muscle of the digits of the same foot was employed. The anterior tibial nerve which supplies these muscles was bared for about two centimeters, severed toward the body, and set in shielded electrodes, around which the skin was fastened by spring clips. Thus the nerve could be protected, kept moist, and stimulated without stimulation of neighboring structures. By a small slit in the skin the tendon of the muscle was uncovered, and after a strong thread was tied tightly about it, it was separated from its insertion. A nerve-muscle preparation was thereby made which was still connected with its proper blood supply. The preparation was fixed firmly to the animal holder by thongs looped around the hock and the foot, i. e., on either side of the slit through which the tendon emerged.

The thread tied to the tendon was passed over a pulley and down to a pivoted steel bar which bore a writing point. Both the pulley and this steel writing lever were supported in a rigid tripod. In the earliest experiments the contracting muscle was made to lift weights (125 to 175 grams); in all the later observations, however, the muscle pulled against a spring attached below the steel bar. The tension of the spring as the muscle began to lift the lever away from the support was, in most of the experiments, 110 grams, with an increase of 10 grams as the writing point was raised 4.5 millimeters. The magnification of the lever was 3.8.

The stimuli delivered to the anterior tibial nerve were, in most experiments, single break shocks of a value barely maximal when applied to the fresh preparation. The rate of stimulation varied between 60 and 300 per minute, but was uniform in any single observation. A rate which was found generally serviceable was 180 per minute.

Since the anterior tibial nerve contains fibres affecting blood vessels, as well as fibres causing contraction of skeletal muscle, the possibility had to be considered that stimuli applied to it might disturb the blood supply of the region. Constriction of the blood vessels would be likely to produce the most serious disturbance, by lessening the blood flow to the muscle. The observations of Bowditch and Warren,[7] that vasodilator rather than vasoconstrictor effects are produced by single induction shocks repeated at intervals of not more than five per second, reassured us as to the danger of diminishing the blood supply, for the rate of stimulation in our experiments never exceeded five per second and was usually two or three. Furthermore, in using these different rates we have never noted any result which could reasonably be attributed to a diminished circulation.

The Splanchnic Preparation

The splanchnic nerves were stimulated in various ways. At first only the left splanchnics in the abdomen were prepared. The nerves, separated from the spinal cord, were placed upon shielded electrodes. The form of electrodes which was found most satisfactory was that illustrated in Fig. 10. The instrument was made of a round rod of hard wood, bevelled to a point at one end, and grooved on the two sides. Into the grooves were pressed insulated wires ending in platinum hooks, which projected beyond the bevelled surface. Around the rod was placed an insulating rubber tube which was cut out so as to leave the hooks uncovered when the tube was slipped downward.

In applying the electrodes the left splanchnic nerves were first freed from their surroundings and tightly ligatured as close as possible to their origin. By means of strong compression the conductivity of the nerves was destroyed central to the ligature. The electrodes were now fixed in place by thrusting the sharp end of the wooden rod into the muscles of the back. This was so done as to bring the platinum hooks a few millimeters above the nerves. With a small seeker the nerves were next gently lifted over the hooks, and then the rubber tube was slipped downward until it came in contact with the body wall. Absorbent cotton was packed about the lower end of the electrodes, to take up any fluid that might appear; and finally the belly wall was closed with spring clips. The rubber tube served to keep the platinum hooks from contact with the muscles of the back and the movable viscera, while still permitting access to the nerves which were to be stimulated. This stimulating apparatus could be quickly applied, and, once in place, needed no further attention. In some of the experiments both splanchnic nerves were stimulated in the thorax. The rubber-covered electrode proved quite as serviceable there as in the abdomen.

The current delivered to the splanchnic nerves was a rapidly interrupted induced current of such strength that no effects of spreading were noticeable. That splanchnic stimulation causes secretion of the adrenal glands has been proved in many different ways which have already been described (see p. 41).

The Effects of Splanchnic Stimulation on the Contraction of Fatigued Muscle

When skeletal muscle is repeatedly stimulated by a long series of rapidly recurring electric shocks, its strong contractions gradually grow weaker until a fairly constant condition is reached. The record then has an even top—the muscle has reached the “fatigue level.” The effect of splanchnic stimulation was tried when the muscle had been fatigued to this stage. The effect which was often obtained by stimulating the left splanchnic nerves is shown in Fig. 11. In this instance the muscle while relaxed supported no weight, and while contracting lifted a weight of 125 grams. The rate of stimulation was 80 per minute.

The muscle record shows a brief initial rise from the fatigue level, followed by a drop, and that in turn by another, prolonged rise. The maximum height of the record is 13.5 millimeters, an increase of 6 millimeters over the height recorded before splanchnic stimulation. Thus the muscle was performing for a short period 80 per cent more work than before splanchnic stimulation, and for a considerably longer period exhibited an intermediate betterment of its efficiency.

The First Rise in the Muscle Record

The brief first elevation in the muscle record when registered simultaneously with arterial blood pressure is observed to occur at the same time with the sharp initial rise in the blood-pressure curve (see Fig. 12). The first sharp rise in blood pressure is due to contraction of the vessels in the area of distribution of the splanchnic nerves, for it does not appear if the alimentary canal is removed, or if the celiac axis and the superior and inferior mesenteric arteries are ligated. The betterment of the muscular contraction is probably due directly to the better blood supply resulting from the increased pressure, for if the adrenal veins are clipped and the splanchnic nerves are stimulated, the blood pressure rises as before and at the same time there may be registered a higher contraction of the muscle.

The Prolonged Rise in the Muscle Record

As Fig. 12 shows, the initial quick uplift in the blood-pressure record is quickly checked by a drop. This rapid drop does not appear when the adrenal veins are obstructed. A similar difference in blood-pressure records has been noted before and after excision of the adrenal glands. As Elliott,[8] and as Lyman and I[9] have shown, this sharp drop after the first rise, and also the subsequent elevation of blood pressure, are the consequences of liberation of adrenal secretion into the circulation. Fig. 12 demonstrates that the prolonged rise of the muscle record begins soon after this characteristic drop in blood pressure.

If after clips have been placed on the adrenal veins so that no blood passes from them, the splanchnic nerves are stimulated, and later the clips are removed, a slight but distinct improvement in the muscular contraction occurs. As in the experiments of Young and Lehmann,[10] in which the adrenal veins were tied for a time and then released, the release of the blood which had been pent in these veins was quickly followed by a rise of blood pressure. The volume of blood thus restored to circulation was too slight to account for the rise of pressure. In conjunction with the evidence that splanchnic stimulation calls forth adrenal secretion, the rise may reasonably be attributed to that secretion. The fact should be noted, however, that in this instance the prolonged improvement in muscular contraction did not appear until the adrenal secretion had been admitted to the general circulation.

Many variations in the improvement of activity in fatigued muscle after splanchnic stimulation were noted in the course of our investigation. The improvement varied in degree, as indicated by increased height of the record. In some instances the height of contraction was doubled—a betterment by 100 per cent; in other instances the contraction after splanchnic stimulation was only a small fraction higher than that preceding the stimulation; and in still other instances there was no betterment whatever. Never, in our experience, were the augmented contractions equal to the original strong contractions of the fresh muscle.

The improvement also varied in degree as indicated by persistence of effect. In some instances the muscle returned to its former working level within four or five minutes after splanchnic stimulation ceased (see Fig. 11); and in other cases the muscle continued working with greater efficiency for fifteen or twenty minutes after the stimulation.

The Two Factors: Arterial Pressure and Adrenal Secretion

The evidence just presented has shown that splanchnic stimulation improves the contraction of fatigued muscle. Splanchnic stimulation, however, has two effects—it increases general arterial pressure and it also causes a discharge of adrenin from the adrenal glands. The questions now arise—Does splanchnic stimulation produce the improvement in muscular contraction by increasing the arterial blood pressure and thereby flushing the laboring muscles with fresh blood? Or does the adrenin liberated by splanchnic stimulation act itself, specifically, to improve the muscular contraction? Or may the two factors coöperate? These questions will be dealt with in the next two chapters.

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