Whether circulating sugar can be immediately utilized by active muscles has been a subject of dispute. The claim of Chauveau and Kaufmann[11] that a muscle uses about three and a half times as much blood sugar when active as when resting, although supported by Quinquaud,[12] and by Morat and Dufourt,[13] has been denied by Pavy,[14] who failed to find any difference between the sugar content of arterial and venous blood when the muscle was contracting; and also by Magnus-Levy,[15] who has estimated that the amount of change in sugar content of the blood passing through a muscle must be so slight as to be within the limits of the error of analysis. On the other hand, when blood or Ringer’s solution is repeatedly perfused through contracting heart muscle, the evidence is clear that the contained sugar may more or less completely disappear. Thus Locke and Rosenheim[16] found that from 5 to 10 centigrams of dextrose disappeared from Ringer’s solution repeatedly circulated through the rabbit heart for eight or nine hours. And recently Patterson and Starling[17] have shown that if blood is perfused repeatedly through a heart-lung preparation for three or four hours, and the heart is continually stimulated by adrenin added to the blood, the sugar in the blood wholly vanishes; or if the supply of sugar is maintained, the consumption may rise as high as 8 milligrams per gram of heart muscle per hour—about four times the usual consumption. When an animal is eviscerated it may be regarded as a preparation in which the muscles are perfused with their proper blood, pumped by the heart and oxygenated by the lungs. Under these circumstances, the percentage of sugar in the blood steadily falls,[18] because the utilization by the tissues is not compensated for by further supply from the liver. Thus, although there may be doubt that analyses of sugar in the blood flowing into and out from an active muscle during a brief period can be accurate enough to prove a clear difference, the evidence from the experiments above cited shows that when the supply of sugar is limited it disappears to a greater or less degree when passed repeatedly through muscular organs.
The argument may be advanced, of course, that the sugar which thus disappears is not directly utilized, but must first be changed to glycogen. There is little basis for this assumption. There is, on the other hand, considerable evidence that increasing the blood sugar does, in fact, directly increase muscular efficiency. Thus Locke[19] proved that if oxygenated salt solution is perfused through the isolated rabbit heart, the beats begin to weaken after one or two hours; but if now 0.1 per cent dextrose is added to the perfusing liquid, the beats at once become markedly stronger and may continue with very slow lessening of strength as long as seven hours. And Schumberg[20] noted that when he performed a large amount of general bodily work (thus using up blood sugar) and then tested flexion of the middle finger in an ergograph, the ability of the muscle was greater if he drank a sugar solution than if he drank an equally sweet solution of “dulcin.” He did not know during the experiment which solution he was drinking. These observations have been confirmed by Prantner and Stowasser, and by Frentzel.[21] In experiments on cats, Lee and Harrold[22] found that when sugar is removed from the animal by means of phlorhizin the tibialis anticus is quickly fatigued; but if, after the phlorhizin treatment, the animal is given an abundance of sugar and then submitted to the test, the muscle shows a much larger capacity for work. All this evidence is, of course, favorable to the view that circulating sugar may be quickly utilized by contracting muscles.
From the experimental results presented above it is clear that muscles work preferably by utilizing the energy stored in sugar, that great muscular labor is capable of considerably reducing the quantity of stored glycogen and of circulating sugar, and that under circumstances of a lessened sugar content the increase of blood sugar considerably augments the ability of muscles to continue contracting. The conclusion seems justified, therefore, that the increased blood sugar attendant on the major emotions and pain would be of direct benefit to the organism in the strenuous muscular efforts involved in flight or conflict or struggle to be free.
The Utility of Increased Adrenin in the Blood as an Antidote to the Effects of Fatigue
The function which the discharged adrenin itself might have in favoring vigorous muscular contraction has already been suggested in the chapter on the effect of adrenin in restoring the irritability of fatigued muscle. Some of the earliest evidence proved that removal of the adrenal glands has a debilitating effect on muscular power, and that injection of adrenal extract has an invigorating effect. For these reasons it seemed possible that increased adrenal secretion, as a reflex result of pain or the major emotions, might act in itself as a dynamogenic factor in the performance of muscular work. It was on the basis of that possibility that Nice and I tested the effect of stimulating the splanchnic nerves (thus causing adrenal secretion), or injecting adrenin, on the contraction of the fatigued tibialis anticus. We found, as already described, that when arterial pressure was of normal height, and was prevented from rising in the legs while the splanchnic was being stimulated, there was a distinct rise in the height of contraction of the fatigued muscle. And we drew the inference that adrenin set free in the blood may operate favorably to the organism by preparing fatigued muscles for better response to the nervous discharges sent forth in great excitement.
This inference led to the experiments by Gruber, who examined the effects of minute amounts of adrenin (0.1 or 0.5 cubic centimeter, 1:100,000), and also of splanchnic stimulation, on the threshold stimulus of fatigued neuro-muscular and muscular apparatus. Fatigue, the reader will recall, raises the threshold not uncommonly 100 or 200 per cent, and in some instances as much as 600 per cent. Rest will restore the normal threshold in periods varying from fifteen minutes to two hours, according to the length of previous stimulation. If a small dose of adrenin is given, however, the normal threshold may be restored in three to five minutes.
From the foregoing evidence the conclusion is warranted that adrenin, when freely liberated in the blood, not only aids in bringing out sugar from the liver’s store of glycogen, but also has a remarkable influence in quickly restoring to fatigued muscles, which have lost their original irritability, the same readiness for response which they had when fresh. Thus the adrenin set free in pain and in fear and rage would put the muscles of the body unqualifiedly at the disposal of the nervous system; the difficulty which nerve impulses might have in calling the muscles into full activity would be practically abolished; and this provision, along with the abundance of energy-supplying sugar newly flushed into the circulation, would give to the animal in which these mechanisms are most efficient the best possible conditions for putting forth supreme muscular efforts.[*]
[*] If these results of emotion and pain are not “worked off” by action, it is conceivable that the excessive adrenin and sugar in the blood may have pathological effects. (Cf. Cannon: Journal of the American Medical Association, 1911, lvi, p. 742.)
The Question Whether Adrenin Normally Secreted Inhibits the Use of Sugar in the Body
The only evidence opposed to the conclusion which has just been drawn is that which may be found in results recently reported by Wilenko. He injected adrenin into urethanized rabbits, usually one milligram per kilo body weight, and then found that the animals did not oxidize any part of an intravenous injection of glucose. Rabbits supplied with glucose in a similar manner, but not given adrenin, have an increased respiratory quotient. Wilenko[23] concluded, therefore, that adrenin lessens the capacity of the organism to burn carbohydrates. In a later paper he reported that adrenin, when added, with glucose, to physiological salt solution (Locke’s), and perfused through the isolated rabbit heart, notably increases the use of sugar by the heart (from 2.2–2.8 to 2.9–4.3 milligrams of glucose per gram of heart muscle per hour), but that the heart removed after the animal has received a subcutaneous injection of adrenin uses much less sugar, only 0.5–1.2 milligrams per gram per hour. From these results Wilenko[24] concludes that the glycosuria following injection of adrenin is the result of disturbance of the use of sugar—an effect which is not direct on the sugar-consuming organ, but indirect through action on some other organ.