Protective effects of dimethyl-propranolol (UM-272) during global ischemia of isolated feline hearts.
This study was designed to determine the effects of dimethyl-propranolol (UM-272) on myocardial injury after global ischemia of isolated feline hearts. Untreated ischemic hearts developed contracture, resulting in a leftward shift of the diastolic pressure-volume curve. Active pressure development in perfused ischemic hearts was significantly depressed compared to preischemic values. Untreated ischemic hearts exhibited increased water, sodium (Na+) and calcium (Ca++) contents and depletion of potassium (K+). The Ca++ accumulating ability of cardiac microsomal fractions isolated from untreated ischemic hearts was severely depressed. In hearts treated with UM-272, active ventricular pressure development after ischemia declined to the same extent as in untreated hearts, but ischemic contracture in treated hearts was delayed and completely reversed by reperfusion. Treated hearts were not depleted of K+ and changes in Na+ and Ca++ were significantly less than in untreated hearts. Microsomal Ca++ accumulation in the treated group was well preserved compared to that in untreated hearts. Experiments in which hearts were paced during UM-272 administration suggest that decreased myocardial oxygen consumption contributes substantially to the protective effects of UM-272. In addition, UM-272 may protect the ischemic heart through direct effects on myocardial Ca++ regulating mechanisms.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002415:Cats; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011312:Pressure; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011674:Pulse / Q000187:drug effects
D004573:Electrolytes; C002616:pranolium; D011433:Propranolol; D002118:Calcium