Effects of diltiazem on experimental myocardial ischemia and on left ventricular performance

To assess the influence of diltiazem on perfusion and function of the ischemic myocardium, 22 conscious chronically instrumented dogs were studied during a 4-hour coronary artery occlusion. Eleven dogs received diltiazem, 20 micrograms/kg per min, for 15 minutes beginning 5 minutes after coronary occlusion, followed by 10 micrograms/kg per min for 4 hours; 11 control dogs received saline. Heart rate was derived from lead 2 of the electrocardiogram; left ventricular pressures and max dp/dt were measured from a high fidelity pressure micromanometer; regional systolic shortening expressed as percent of end-diastolic length (% delta L) was calculated from multiple pairs of ultrasonic crystals implanted subendocardially; regional coronary blood flow was measured with 15 microns microspheres. The product of heart rate X peak left ventricular systolic pressure was significantly decreased after 90 minutes of infusion of diltiazem. In the diltiazem-treated group, % delta L of the nonischemic segments was significantly decreased after 120 minutes of treatment. There was no significant recovery of function of the dyskinetic segments in either group. The hypokinetic segments recovered significantly after 120 minutes in the diltiazem-treated group. There was no improvement of function in the hypokinetic segments of the control group. Myocardial blood flow was significantly increased by diltiazem in the hypokinetic segments with an increase in the endocardium:epicardium ratio. We conclude that diltiazem, early after coronary occlusion, improves the function of ischemic segments that are not dyskinetic. The mechanisms involved are an increase of collateral blood flow with a redistribution to the subendocardium and a decrease of myocardial oxygen consumption.