The effects of three different plasma levels of
verapamil on coronary hemodynamics and myocardial metabolism in the presence of 1.61 +/- 0.05% end-tidal concentration of
isoflurane (mean +/- SEM) were studied in a canine model, using a thermodilution coronary sinus
catheter to measure coronary sinus blood flow and pressure and to provide coronary sinus plasma samples. A control group receiving only
isoflurane was also studied (n = 6). Plasma arterial
verapamil levels of 55 +/- 7 (n = 6); 134 +/- 7 (n = 10); and 301 +/- 37 ng X ml-1 (n = 5), were achieved by a loading dose followed by a continuous infusion for 30 min. The only changes with time in the
isoflurane group were decreases in left ventricular maximum rate of tension development (dP/dt) and left ventricular
stroke work index compared with control after 90 min without changes in myocardial
oxygen balance. The low plasma
verapamil level caused reductions in heart rate, mean and diastolic arterial pressure, and left ventricular dP/dt without changes in myocardial
oxygen supply or myocardial metabolism. Intermediate
verapamil concentrations produced a transient initial increase in heart rate and a reduction in stroke volume index. With the intermediate and the highest levels of
verapamil, mean and diastolic arterial pressure, left ventricular dP/dt, and cardiac index were decreased. An increase in arterial
norepinephrine plasma levels was seen in the intermediate and the highest levels of
verapamil; however, a transient coronary vasodilation occurred without changes in myocardial
oxygen balance. Significant prolongation of the PR interval was observed in all
verapamil groups, with second or third degree
heart block in some of the higher-dose animals.(ABSTRACT TRUNCATED AT 250 WORDS)