Pathogenesis of "electrolyte-steroid-cardiopathy".

1 reported that the combined administration of 2a-methyl-9a-chlorocortisol and sodium phosphate could induce focal necrotic lesions of the myocar-dium. This report was followed by a large number of papers from the same laboratory in which it was reported that many, but not all, adrenal cortical steroids could act in the same way as 2a-methyl-9a-chlorocortisol and that the sodium salts of certain other anions could be substituted for phosphate in the production of the myocardial lesions. Administration of the steroid or of the electrolyte alone did not produce lesions. These observations led to the postulation of specific interactions between the ions and the steroid in the form of "sensitizing" or "conditioning" of the organism to the action of one agent by the other, and of specific interactions and an-tagonisms of the cellular (myocardial) "tox-icities" of the various ions. Much of this material now has been summarized in book form. 2 The present studies were undertaken because of our interest in three factors associated with the production of "electrolyte-steroid" myocardial necrosis, which became apparent from a survey of the many scattered reports. (1) The most effective steroids are those which strongly influence electrolyte distribution and excretion. (2) Sodium phosphate and sodium sulfate administered orally are among the electrolytes most effective in inducing myocardial lesions, although they are poorly absorbed and are known to be effective cathartics. (3) The myocardial lesions can be prevented by the administration of potassium. It therefore appeared to us possible that the " electrolyte-steroid-cardiopathy " might be simply an expression of potassium deficiency caused by the simultaneous steroid-induced renal loss and saline cathartic-induced gastrointestinal loss of the ion. Methods Female Sprague-Dawley rats weighing 100 to 125 Gm. were employed in all experiments. The steroid used was 2a-methyl-9a-chloroeortisol acetate , which has a very potent effect on sodium and potassium balance and distribution, administered subeutaneously in a daily dose of 100 /xg. suspended in 0.2 ml. of water. Chlorothiazide HC1, 15 to 50 mg./Kg. given subeutaneously twice daily, was substituted for the steroid in one experiment. Various groups of animals also received twice daily 0.2, 0.4, or 0.5 mil of Na 2 SO 4 in 0.5 to 1.25 ml. subeutaneously, or 1.0 mM Na 2 SO 4 in 5 ml. of water, 125 mg. of a carboxylie acid cation exchange resin (CTS-21, hydrogen cycle), 0.5 to 5.0 ml. of castor oil, or 6.25 to 0.5 ml. of 25 per …