Combined Effects of Volatile Anesthetics and Phosphodiesterase Inhibitors on Contractile Performance in Guinea Pig Hearts

Abstract

The cardiotonic effects of the phosphodiesterase inhibitors amrinone, milrinone, and 3-isobutyl-1-methylxanthine were studied in Langendorff-perfused guinea pig hearts exposed to the cardiodepressant concentrations of halothane or isoflurane. Left ventricular pressure, rate of change of pressure (dP/dt), heart rate, and perfusion pressure were measured in the presence of increasing drug concentrations. Under control conditions, both (dP/dt)max and heart rate were increased most with 3-isobutyl-1-methylxanthine and least with amrinone. In isoflurane-pretreated hearts (1.3%, vol/vol), the phosphodiesterase inhibitors increased (dP/dt)max to a larger degree, whereas the increase in heart rate remained similar to that in the control hearts. After exposure to halothane (0.8%, vol/vol), however, amrinone and milrinone were less effective with respect to enhancement of contractile performance. There was no difference in the 3-isobutyl-1-methylxanthine-induced increase of (dP/dt)max between hearts exposed to isoflurane and those exposed to halothane. Our results suggest that contractile performance of isolated hearts is more easily stimulated by milrinone and amrinone in the presence of isoflurane than in the presence of halothane.