Sustained coronary constriction and its antagonism by calcium-blocking agents in monkeys and baboons

Experiments were performed on five Japanese monkeys and one anubis baboon anesthetized initially with ketamine hydrochloride and subsequently with sodium pentobarbital, and maintained on artificial respiration. The left anterior descending coronary artery (LAD) was cannulated and its vascular bed was perfused with arterial blood. Perfusion pressure was kept constant at a value slightly higher than the mean systemic arterial pressure. Blood flow through the LAD was measured by an electromagnetic flow meter. All drugs were administered into the LAD. Single injections of acetylcholine produced a biphasic change in blood flow; an initial decrease (vasoconstriction) followed by an increase (vasodilation). Infusion of acetylcholine produced a sustained decrease in blood flow in all the animals used except one Japanese monkey in which oscillatory changes in blood flow were induced. With infusions of acetylcholine, however, left ventricular pressure (LVP), and maximum rate of rise of LVP (LV dP/dt max), heart rate, and systemic arterial pressure remained unchanged. Single injections of diltiazem and nifedipine, calcium-blocking agents, and nitroglycerin produced a dose-related increase in blood flow. Diltiazem and nifedipine exerted no effects on other cardiohemodynamic variables, whereas nitroglycerin produced a decrease in systemic arterial pressure and an increase in heart rate. When blood flow through the LAD was reduced to nearly half of the basal value by infusion of acetylcholine, diltiazem and nifedipine produced an increase in blood flow as much as in control, whereas nitroglycerin produced less of an increase than in control.