J.Jpn. Surg. Soc.. 60(5): 759-775, 1959
EFFECT OF ARTIFICIAL HIBERNATION ON PITUITARY ADRENOCORTICAL ACTIVITY AND ITS RESPONSE TO SURGICAL AGRESSION
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2nd Surgical Department, Tokyo University School of Medicine Yoshihide FUJIMOTO |
Results obtained were as follows:
1) Chlorpromazine itself caused adrenal ascorbic acid depletion, elevation of plasma 17-hydroxycorticosteroid level, increase of corticoid secretion into the adrenal venous blood, and decrease of circulating eosinophiles. Leucocyte count also decreased after chlorpromazine administration, but rebound increase was noted after 3 to 4 hours, despite the continuous fall of eosinophile count.
Gomori-positive substance markedly decreased immediately after intravenous injection of chlorpromazine. Adrenal asocorbic acid depletion produced by chlorpromazine was not observed in the hypophysectomized rats.
2) The intramuscular injection of 0.5 mg/100 g b.w. of chlorpromazine blocked the adrenal ascorbic acid depletion in rats caused by unilateral adrenalectomy, but not effectively inhibited the depletion by manipulation of intestines and by hemorrhage. Chlorpromazine of the same dose, when administered intravenously, effectively inhibited the response to surgical agreessions mentioned above, and the intravenous injection of the dose was enough for almost every rat to be acutely collapsed.
Data obtained from 5 patients operated under artificial hibernation showed similar responses to surgery of circulating eosinophile count, urinary excretion of corticoids and blood sugar level as those responses of 8 patients operated under the anesthesia without chlorpromazine. However, the extreme increase of plasma 17-hydroxycortico steroid and serum cholinesterase level during 4 to 8 hours following surgery was moderately depressed in the former group.
Chlorpromazine did not significantly inhibit the increas of 17-hydroxycorticosteroid secretion into the adrenal venous blood in dogs following the adrenal vein cannulation, which was a moderately severe surgical agression.
Inhibitory effect of chlorpromazine was observed at the level of hypothalamus and pituitary gland by determinations of both neuro-secretion and action current in dogs. Exogenous ACTH caused marked decrease of adrenal ascorbic acid content in rats, treated by chlorpromazine of enough dose to inhibit the response to stress.
3) In hypothermia with or without chlorpromazine, the pituitary-aclrenocortical activity was decreased and response to surgical agression was also strongly depressed.
4) Chlorprornazine did not affect the half-life of administered hydrocortisone. In hypothermia, conjugation of free 17-hydroxycorticysteroids in the liver was presumed to be retarded.
From these results, it is concluded that chlorpromazin produces a trancient pituitary-adrenocortical hyperactivity, acting on the hypothalamus, and after a interval, when a relativaly large dose of chlorpromazine is injected rapidly into vein in experimental animals, chlorpromazine effectively inhibits the pituitary-adrenocortical response to surgical agression. However, the intramuscular or slow intravenous administration of chlorpromazine of clinical dose does not significantly depress the adrenocortical hyperfunction produced by stress, unless the body temperature is lowered under about 27 degree C.
(author's abstract)
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