COMPARISON OF THE EFFECTS OF ENDOTHELIN AND BAY-K-8644 ON CARDIOHEMODYNAMICS IN ANESTHETIZED PIGS

The effects of endothelin on cardiohemodynamics in anesthetized open-chest pigs were compared with those of the Ca2+ channel agonist Bay k 8644. I.v. administration of endothelin (0.1-1-mu-g/kg) dose relatedly decreased coronary blood flow velocity (CFV), cardiac output, the maximal rate of rise in left ventricular pressure (LV dP/dt(max)) and heart rate, and increased systolic and diastolic blood pressure and systemic vascular resistance. Bay k 8644 (0.1-30-mu-g/kg) showed similar effects on cardiohemodynamics, except that it caused a substantial increase in LV dP/dt(max) and did not change stroke volume. I.c. administration of endothelin (0.1-1-mu-g) into the left circumflex coronary artery (LCX) produced a dose-dependent and sustained decrease in CFV followed by a marked increase in the ST segment of epicardial electrocardiograms and a depression in myocardial shortening in the region supplied by LCX. An increase in left ventricular end-diastolic pressure and a reduction in LV dP/dt(max) were also observed after endothelin. In contrast, Bay k 8644 caused a transient decrease in CFV and an increase in LV dP/dt(max), without causing any changes indicative of myocardial ischemia. Although the reduction in CFV after i.c. endothelin was not affected by i.v. infusion of nicardipine (1-mu-g/kg per min), the reduction in CFV observed after i.c. Bay k 8644 was significantly suppressed (P < 0.05). We conclude that endothelin is a more potent coronary vasoconstrictor than Bay k 8644 and provokes marked myocardial ischemia.