H. Selye

Simple Techniques for the Surgical Occlusion of Coronary Vessels in the Rat

From the Institut de Médecine et de Chirurgie expérimentales, Université de Montréal, Montreal, Canada. * The essence of this communication was presented to the International College of Angiology at a Meeting held in Montreal, February 20, 1960. t Fellow of the Gustavus and Louise Pfeiffer Research Foundation.

Protection, by coronary ligature, against isoproterenol-induced myocardial necroses.

Fellow of the Rotary Club (D 191). Experimental coronary occlusion has been studied extensively in large laboratory animals, but these subjects do not lend themselves well to the large-scale testing of surgical procedures and drugs that may be useful in the prophylaxis

Role of local trauma in production of cutaneous calcinosis by dihydrotachysterol.

Summary Experiments on rats indicate that, following occlusion of the left coronary artery near its origin, the myocardium outside resulting infarct becomes unusually resistant to production of diffuse cardiac necroses by isoproterenol.

Humoral conditioning for production of acute, massive myocardial necroses by neuromuscular exertion.

Summary In rats, a cutaneous calcinosis with sclerosis, not unlike that seen in certain types of clinical scleroderma, can be produced at will in predetermined regions of the skin. This is best accomplished if, at a critical time of systemic dihydrotachysterol overdosage, the selected cutaneous area is lightly traumatized by epilation.

Various types of calcinosis induced by egg albumen or yolk following sensitization with dihydrotachysterol (DHT).

Summary Following pretreatment with 2-methyl-9(α)-chlorocortisol (Me-Cl-COL), a brief period of neuromuscular effort (induced by force restraint) can elicit acute, massive myocardial necroses in the rat. When NaH2PO4 was administered in addition to Me-Cl-COL during the pretreatment period, such changes occurred in 100% of the experimental animals, during or immediately after a period of forced restraint.

Role of sodium in production of myocardial necroses by stress.

Summary In rats previously sensitized by a single oral dose of dihydrotachysterol (DHT), massive and rather selective calcification of the pancreas is induced by subsequent intraperitoneal administration of egg white. Intravenous injection of egg yolk elicits a calcinosis primarily affecting the reticuloendothelial cells of the liver and the spleen. Yet, other types of calcinosis are induced by intravenous injection of egg white or the intraperitoneal administration of egg yolk. It is assumed that albumen and yolk act as “vital mordants,” preparing the tissues of suitably sensitized animals for the subsequent uptake of calcium, distribution of the lesions being dependent upon the special distribution patterns of the mordants themselves.

Cyst formation in the parathyroids and muscular dystrophy induced by dihydrotachysterol and calcium acetate.

Summary Certain Na-salts (chloride, acetate, citrate and lactate) are well tolerated even by rats simultaneously treated with 2α-methyl-9α-chlorocortisol (Me-Cl-COL) or a severe stressor, such as forced restraint. However, these same salts produce massive and sometimes fatal myocardial necroses, in rats exposed to the stress of forced restraint after conditioning with Me-Cl-COL. It appears that during stress the metabolism of certain otherwise innocuous Na-salts and/or steroids is so altered that they acquire severe cardio-toxic properties.

Sensitization by Thallium to Dihydrotachysterol Overdosage.

Summary Experiments on rats indicate that oral administration of dihydrotachyster-o1 (DHT) plus calcium acetate, regularly induces extensive cyst formation in the parathyroids, associated with widespread degenerative changes in the skeletal musculature. Under the conditions of these experiments, neither DHT nor calcium acetate alone produced such changes.

Abolition by hypophysectomy of the anticortisol action of desoxycorticosterone.

Summary A single dose of thallium acetate, which in itself produces no detectable organ lesions in the rat, causes severe nephrocalcinosis strictly limited to the corticomedullary junction line if an otherwise non-nephrotoxic dose of dihydrotachysterol (DHT) is administered simultaneously. The DHT-induced calcification in aorta and in traumatized skin regions is greatly aggravated by concurrent treatment with thallium acetate. This sensitizing effect of thallium acetate cannot be ascribed to its stressor action, since under comparable circumstances, exposure to stress (restraint) actually prevents the manifestations of DHT-intoxication.

Calciphylactic Muscular Dystrophy Induced by DHT plus 5HT.

Summary Hypophysectomy, with or without adrenalectomy, abolishes the anticortisol effects (upon catabolism inflammation, thymolysis and splenolysis) of desoxycorticosterone acetate, seen in the adrenalectomized rat. Apparently, the anticortisol actions of mineralocorticoids are indirect, and depend upon some hypophyseal conditioning factor.