REFERENCES
[1] Kleen: On Diabetes Mellitus and Glycosuria, Philadelphia, 1900, pp. 22, 37–39.
[2] Naunyn: Der Diabetes Mellitus, Vienna, 1898, p. 72.
[3] Schultze: Verhandlungen der Gesellschaft deutscher Naturforscher und Aerzte, Cologne, 1908, ii, p. 358.
[4] Zeitschrift für Heilkunde, 1902, xxiii, Abtheilung iii, pp. 14, 19.
[5] Mita: Monatshefte für Psychiatrie und Neurologie, 1912, xxxii, p. 159.
[6] Folin, Denis and Smillie: Journal of Biological Chemistry, 1914, xvii, p. 519.
[7] Arndt: Zeitschrift für Nervenheilkunde, 1897, x, p. 436.
[8] Naunyn: Loc. cit., p. 73; Hirschfeld: Die Zuckerkrankheit, Leipzig, 1902, p. 45.
[9] Waterman and Smit: Archiv für die gesammte Physiologie, 1908, cxxiv, p. 205.
[10] Henderson and Underhill: American Journal of Physiology, 1911, xxviii, p. 276.
[11] Böhm and Hoffmann: Archiv für experimentelle Pathologie und Pharmakologie, 1878, viii, p. 295.
[12] Eckhard: Zeitschrift für Biologie, 1903, xliv, p. 408.
[13] Loewy and Rosenberg: Biochemische Zeitschrift, 1913, lvi, p. 114.
[14] See Abderhalden: Handbuch der biochemischen Arbeitsmethoden, Berlin, 1910, ii, p. 181.
[15] Scott: American Journal of Physiology, 1914, xxxiv, p. 283.
[16] Cited by Scott: Loc. cit., p. 296.
[17] Rolly and Oppermann: Biochemische Zeitschrift, 1913, xlix, p. 201. Jacobsen: Ibid., 1913, li, p. 449. Hirsch and Reinbach: Zeitschrift für physiologische Chemie, 1913, lxxxvii, p. 122.
[18] Cited by Kleen: Loc. cit., p. 37.
[19] Folin, Denis and Smillie: Loc. cit., p. 520.
[20] See Macleod: American Journal of Physiology, 1907, xix, p. 405, also for other references to literature.
[21] See Meyer: Comptes rendus de la Société de Biologie, 1906, lviii, p. 1123; Nishi: Archiv für experimentelle Pathologie und Pharmakologie, 1909, lxi, p. 416.
[22] Gautrelet and Thomas: Comptes rendus de la Société de Biologie, 1909, lxvii, p. 233; and Macleod: Proceedings of the Society for Experimental Biology and Medicine, 1911, viii, p. 110 (true for left adrenal and left splanchnic).
[23] Wertheimer and Battez: Archives Internationales de Physiologie, 1910, ix, p. 392.
CHAPTER VI
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.
[*] These earlier investigations, in which an extract of the entire gland was used, made no distinction between the action of the medulla and that of the cortex. It may be that the weakness following removal or disease of the adrenals is due to absence of the cortex (see Hoskins and Wheelon: American Journal of Physiology, 1914, xxxiv, p. 184). Such a possible effect, however, should not be confused with the demonstrable influence of injected adrenin (derived from the adrenal medulla alone) and the similar effects from adrenal secretion caused by splanchnic stimulation.
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.