Diltiazem was administered to dogs by an intravenous infusion protocol, which resulted in plasma levels of 71 +/- 6 (n = 7), 139 +/- 9 (n = 7), 353 +/- 33 (n = 10), and 1064 +/- 143 (n = 6) ng/ml, to evaluate the effects of diltiazem on cardiovascular function and coronary hemodynamics in the presence of anesthetic concentrations of enflurane. An additional group of six dogs received enflurane only. The only changes observed with enflurane alone were a decrease in left ventricular (LV) dP/dt, cardiac index (CI), and coronary blood flow 60 min after the baseline measurements were made. In all of the diltiazem groups, plasma level-related prolongation of the PR interval of the electrocardiogram was observed, with development of second degree heart block and junctional rhythms in animals at the two higher plasma levels. Mean arterial pressure and LV dP/dt decreased at the two higher diltiazem plasma levels after 30 min of infusion, and three of six dogs in the highest group had to be dropped from the study because of severe hypotension. The cardiac index was no different from enflurane alone with the three lower plasma diltiazem levels. No changes were observed in coronary sinus blood flow, coronary vascular resistance, myocardial oxygen uptake, or myocardial lactate extraction. Circulating norepinephrine levels were elevated in the two higher diltiazem groups.(ABSTRACT TRUNCATED AT 250 WORDS)