Changes in Cardiac Mechanics and Coronary Blood Flow of Regionally Ischemic Porcine Myocardium Induced By Diltiazem

¹ From the Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati

The effect of diltiazem on the relationship between myocardial blood flow and regional myocardial mechanical performance was examined in nine open-chest anesthetized pigs of mixed breed and sex, weighing 20 to 32 kg. A transmural ischemic region of the left ventricular anterior free wall was created by acute ligation of three or four terminal branches of the left anterior descending coronary artery. Regional myocardial mechanics measured by implanted sonomicrometers and regional myocardial blood flow measured by 15 µ radionuclide-labeled microspheres were made during 5 to 60 minutes of coronary ligation. Regional epicardial blood flow in normal and moderately and severely ischemic myocardium was 120±10, 55±10, 5±2 ml/min/100 g, and was 84±14, 32±3 and 9±3 ml/min/100) g in endocardium in the respective regions. The endocardial to epicardial ratio was .69±.09 for normal myocardium and .71±.15 for moderately ischemic myocardium. Analysis of 2-mm sequential sections of the left ventricular anterior free wall indicated that a precipitous margin of 2 mm in width existed between normally perfused myocardium and severely ischemic myocardium. Diltiazem 20 to 80 µg/min/kg, significantly increased blood flow by 20 percent to 80 percent in all regions of normal and ischemic myocardium that had detectable flow by the microsphere technique without modifying the transmural flow distribution or inducing a coronary "steal," while slightly increasing regional myocardial shortening. In conclusion, the acutely ischemic pig myocardium that lacks collaterals and presents a sharp demarcation between transmural ischemic and normal myocardium shows a vasodilator reserve that is recruited by the calcium antagonist, diltiazem, in all regions where blood flow is detectable by the microsphere technique. Diltiazem improves myocardial blood flow at ischemic margins without concomitant myocardial depression typical of other calcium antagonists. Thus, diltiazem may prove useful in the prevention of acute myocardial infarct extension during the acute phases of myocardial ischemia.