Effects of epinephrine and phosphodiesterase III inhibitors on bupivacaine-induced myocardial depression in guinea-pig papillary muscle

Abstract

This study was designed to investigate the effects of epinephrine and the phosphodiesterase III inhibitors amrinone and milrinone on bupivacaine-induced myocardial depression in guinea-pig papillary muscles using an electrophysiological method. Electrophysiological studies of the effects of bupivacaine, epinephrine, amrinone and milrinone in normal and high K(+) Tyrode's solution were measured with guinea-pig papillary muscles. Specifically, epinephrine, amrinone and milrinone reversal of bupivacaine-induced depression was measured. Bupivacaine reduced the action potential duration (APD), the maximum rate of rise of the AP (V(max)) and contractile force. Although epinephrine increased the contractile force similarly to amrinone and milrinone, it shortened the APD at 50% repolarization (APD(50)) and 90% repolarization (APD(90)). A high concentration of amrinone shortened APD, while milrinone did not affect APD except for a prolongation of APD(20). In high K(+) Tyrode's solution (25 mM), epinephrine, amrinone and milrinone increased the APD and the contractile force. Epinephrine reversed bupivacaine depression of APD and contractile force to control levels. Amrinone and milrinone restored not only the contractile force but also APD. There was an incomplete recovery of APD(50) for amrinone and the prolongation of APD(20) for milrinone. Our results suggest that bupivacaine decreases the Ca(+) current (I(Ca)) and Na(+) current (I(Na)). Epinephrine and amrinone may increase I(Ca) and the delayed outward current (I(k)), whereas milrinone may increase I(Ca). The profound cardiovascular depression caused by bupivacaine was effectively reversed by amrinone and milrinone in a manner similar to epinephrine.