| Abstract: | Continuous infusions of verapamil and diltiazem were established in halothane-anesthetized dogs (1.15-1.35% end tidal concentration) with or without a concomitant propranolol infusion to investigate changes: in cardiovascular function, in reflex activation as reflected in circulating catecholamine levels, and in the chronotropic response to the exogenously administered beta agonist, isoproterenol. Verapamil plasma levels of approximately 100 and 250 ng X ml-1, diltiazem plasma levels of approximately 140 and 325 ng X ml-1, and propranolol levels of approximately 70 ng X ml-1 were tolerated individually in the presence of halothane, although atrioventricular conduction was prolonged in the verapamil and diltiazem groups. Catecholamine levels were increased in the high verapamil group. However, when propranolol was combined with the lower levels of verapamil or diltiazem, the result was decreased heart rate, blood pressure, left ventricular maximum rate of tension development (dP/dt), and cardiac index with increased systemic vascular resistance. When the attempt was made to proceed to the increased plasma levels of verapamil or diltiazem in the presence of propranolol, 6/6 animals in the verapamil-propranolol group and 4/6 animals in the diltiazem-propranolol group were unable to maintain a mean arterial blood pressure of greater than 50 mmHg, and many developed 2 degrees or higher heart block.(ABSTRACT TRUNCATED AT 250 WORDS) |
