HALOTHANE AND ISOFLURANE DECREASE CALCIUM SENSITIVITY AND MAXIMAL FORCE IN HUMAN SKINNED CARDIAC FIBERS

Background. Reports of the direct effects of volatile anesthetics on c ardiac myofibrils, studied in various mammalian species but not in hum ans, have conflicted. To determine whether volatile anesthetics direct ly affect cardiac contractile proteins in humans, we examined the effe cts of various equi-anesthetic doses of halothane (0.46, 0.83, and 1.2 3 mm, equivalent to 0.75, 1.50, and 2.25%, respectively) and isofluran e (0.63, 1.22, and 1.93 mm, equivalent to 1.15, 2.30, and 3.50%, respe ctively) on the Ca2+ sensitivity and maximal force in human skinned ca rdiac fibers. Methods: Left ventricular muscle strips were obtained fr om seven patients undergoing cardiac surgery. Sarcolemma was disrupted with EGTA (ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetr aacetic acid), and sarcoplasmic reticulum was destroyed with EGTA plus BRIJ 58 detergent. Ca2+ sensitivity was studied by observing the isom etric tension developed by skinned fiber bundles challenged with solut ions of increasing Ca2+ concentrations expressed in pCa (where pCa = - log10[Ca2+]). Maximal force was measured with a pCa 4.8 solution. Resu lts: Both anesthetics shifted the pCa-tension curves toward higher Ca2 + concentrations and decreased pCa for half-maximal activation in a do se-dependent and reversible fashion (from 5.71 for control to 5.56 and 5.55 for 1 MAC halothane and isoflurane, respectively) without changi ng the slope of this relationship (Hill coefficient). No differences b etween agents were observed at equianesthetic concentrations. The two agents also decreased the maximal activated tension in a dose-dependen t fashion (-27 and -28% vs. control for 2 MAC halothane and isoflurane , respectively). Conclusions: The current study indicates that halotha ne and isoflurane decrease Ca2+ sensitivity and maximal force in human skinned cardiac fibers at 20-degrees-C. If these effects extend to hi gher temperatures, they may contribute to the negative inotropic effec t of these agents.