Effect of diltiazem, a calcium antagonist, on myocardial ischemia.
In line with studies on the metabolism of the ischemic myocardium, the effectiveness of diltiazem hydrochloride, a potent calcium antagonist, in reducing the effects of ischemia was evaluated. Nonischemic and ischemic tissue samples were examined in two groups of dogs--Group I, dogs receiving no drug and killed after 60 minutes of regional ischemia, and Group II, dogs given diltiazem after 10 minutes of ischemia and killed 50 minutes later. Administration of diltiazem proved beneficial in several ways: The decrease in adenosine-5'-triphosphate in the ischemic region was halved, inhibition of anaerobic glycolysis was reduced, tissue levels of lactic acid and free fatty acids were lowered and the contractility of glycerinated heart muscle fibers was improved. However, administration of the drug did not influence mitochondrial function. Mitochondrial oxygen consumption and respiratory control were reduced by equal amounts in both groups, as was mitochondrial calcium ion binding. These observations demonstrate that diltiazem is capable of minimizing the consequences of acute ischemic, although the beneficial effects do not extend to all aspects of myocardial metabolism.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004110:Diltiazem / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010725:Phosphocreatine / Q000378:metabolism
D001552:Benzazepines; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004110:Diltiazem; D002118:Calcium