Cardiovascular failure in experimental adrenal insufficiency: a historical revival.

Abstract

CARDIOVASCULAR FAILURE IN EXPERIMENTAL ADRENAL INSUFFICIENCY: A HISTORICAL REVIVAL R. A. CLEGHORN* The rapid advances in cardiovascular studies in the past 4 decades by themselves have inevitably left many earlier observations stranded like flotsam after a high tide. Perhaps an equal threat to historical continuity may have arisen from the current tendency toward computer search of the literature in which, not merely does much of science appear to have been performed within the last decade or decade and a half, but anything which is not appropriately indexed according to the computer is simply lost. A purpose in the present writing is the conviction that much of the past work, buried apparently beyond the reach of memory, may well have relevance if excavated from tbe dry sands ofjournals where it lies buried. On the chance that studies with which I and others were concerned in the thirties and early forties fall into this category, I have tried to rescue and bring together some of the material which might be of interest to current pundits for heuristic as well as historical reasons. My initial involvement with studies on failing circulation, which turned out to be the core ofthe adrenal insufficiency problem, had to do with physiological investigations concerning the respiratory quotient (R.Q.) and acid-base balance in eviscerated, decerebrate cats in 1930 [1, 2]. The objective was to establish the R.Q. of this muscle preparation. It proved to be about 0.8 prior to depletion of the alkali reserve and a breakdown in circulatory homeostasis. In the following 2 years, my efforts were occupied witb the methods which had just become available for preparing an extract of the adrenal cortex and demonstrating its efficacy by maintaining the life of adrenalectomized cats [3]. The aim The author is indebted to Prof. John Grayson, Department of Physiology, University of Toronto, for his helpful criticisms and suggestions. * Emeritus professor of psychiatry, McGiIl University; consultant, Department of Psychiatry, Sunnybrook Medical Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4H 3M5.© 1983 by The University of Chicago. AU rights reserved. 0031-5982/84/2701-0357$01.00 Perspectives in Biology and Medicine, 27, 1 ¦ Autumn 1983 | 135 was to ascertain the nature of the life-maintaining functions of the adrenal gland which were not known then, though it seemed that death occurred with a decline in the circulation. Concurrent experiments on the influence ofautonomic nerve activity on carbohydrate metabolism in the Aberdeen University laboratory where I worked seemed pertinent. This study, which was reported by Donhoffer and Macleod [4], revealed a role for an adrenal cortex hormone in the autonomic nervous system control of glycogen and sugar release from the liver. Role of the Adrenal Gland ADRENALECTOMY IN THE FROG AND EFFECT OF ADRENAL CORTEX EXTRACTS As a means of investigating the possible relationship between the adrenal cortex and autonomic nervous system, I studied adrenalectomy in frogs, repeating the 1914 experiments of Loewi and Gettwert [5], first, while in the laboratory of the Department of Medicine at the Elizabeth University in Pecs, Hungary, in 1932, and then at the Wilhelmina Gasthuis in Amsterdam (unpublished observations). I found, as had Loewi and Gettwert, that frogs subject to cauterizing of the homologue of the adrenal cortical tissue that lay on the surface of the kidney died after a few days (3-8), showing a terminal bradycardia. At death the heart was in diastole and most of the blood seemed to be in the abdominal vessels at postmortem. Oedema of the peritoneal cavity was frequent due to kidney damage while cauterizing the adrenal tissue. In experiments in which electrical stimulation was applied from head to foot of the adrenalectomized frog, the bradycardia of the adrenal insufficient state appeared sooner. Atropine placed on the heart caused a temporary quickening, but cutting of the vagi had no apparent effect on the downhill course. This suggested that stimulation of the cardioaccelerator (ca.) nerves and their exbaustion was of greater importance than vagal excitation in the development of the bradycardia. In other experiments the isolated frog heart was studied using a Straub cannula perfused with Ringer's solution. It was found that the adrenal cortical extract had a positive inotropic and chronotropic effect...