COMPARATIVE MYOCARDIAL DEPRESSION OF SEVOFLURANE, ISOFLURANE, AND HALOTHANE IN CULTURED NEONATAL RAT VENTRICULAR MYOCYTES

In this study, we compared the direct myocardial depressant effects of sevoflurane, isoflurane, and halothane and determined whether an L-ty pe Ca2+ channel agonist, Bay K 8644, could attenuate the myocardial de pression induced by these anesthetics in cultured neonatal rat ventric ular myocytes. Ventricular myocytes were obtained from neonatal rats b y enzymatic digestion with collagenase and then cultured for 6-7 days. The myocytes were stabilized in serum-free me dun, and the spontaneou s beating rate and contractile amplitude were measured by using a fibe roptic sensor. Each anesthetic deceased the beating rate and amplitude in a concentration-dependent manner (1%-4% vol/vol) (P < 0.001), with halothane decreasing the beating rate and amplitude the most (P < 0.0 1). Isoflurane caused larger decreases in the beating rate than sevofl urane at 3% and 4% (P < 0.05). Potency for suppression of contractile amplitude was in the order of halothane much greater than isoflurane > sevoflurane. However, the myocardial depressant effects of the anesth etics were not different when their concentrations were corrected for minimum alveolar anesthetic concentration values. Bay K 8644 significa ntly prevented the anesthetic-depressed amplitude (P < 0.05). We concl ude that sevoflurane, isoflurane, and halothane have direct myocardial depressant effects on cultured neonatal rat ventricular myocytes and that the reduction of sarcolemmal L-type Ca2+ channel current levels m ediates the myocardial depression observed in these immature hearts. I mplications: Sevoflurane, isoflurane, and halothane have a direct card iodepressant effect on cardiac excitation-contraction coupling in the immature heart, which is mediated by an interaction with the L-type Ca 2+ channel.