Opposing effects of deoxycorticosterone and spironolactone on isoprenaline-induced myocardial infarction.
Adult, male Sprague-Dawley rats were subjected to massive myocardial infarction with isoprenaline. Some of the animals were treated with the potent mineralocorticoid, deoxycorticosterone, or the anti-mineralocorticoid, spironolactone. Autopsies spaced at sequential time intervals demonstrated that circulating levels of enzymes, eg, CPK, SGOT, SGPT and LDH, lipids, eg, triglycerides, free fatty acids, and cholesterol, glucose, Bun, and corticosterone rose in conjunction with on-going necrosis and became lowered in conjunction with myocardial repair. Body and organ weights, ie, adrenal, thymus, heart, and kidney, underwent dynamic changes commensurate with necrosis and repair. Animals given isoprenaline alone died (52% survival) during the height of their massive infarct and congestive heart failure (Days 3 and 4). Animals treated with DOC showed the most severe congestion but died (36% survival) during the late repair phase (Days 7 and 8). Animals treated with spironoloactone showed the most effective clearance of thoracic fluid and also dies (18% survival) during the late repair phase (Days 7 and 8). These spironolactone-treated animals had large, left ventricular aneurysms with organised, adherent thrombi. It is believed that alterations in electrolyte balance induced by DOC or spironolactone caused changes in adrenocortical function which greatly modified the usual pathophysiological response to myocardial infarction.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000494:pharmacology*; D007545:Isoproterenol; D008055:Lipids / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D013148:Spironolactone / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D008055:Lipids; D013148:Spironolactone; D003900:Desoxycorticosterone; D007545:Isoproterenol; D003345:Corticosterone