Halothane and Isoflurane Decrease Calcium Sensitivity and Maximal Force in Human Skinned Cardiac Fibers

TL;DR: In this paper, the effects of halothane (0.46, 0.83, and 1.23 mM, equivalent to 0.75, 1.50, and 2.25%, respectively) and isoflurane ( 0.63, 1., 1.30, and 3.50), respectively, on the Ca 2+ sensitivity and maximal force in human skinned cardiac fibers were examined.

Abstract: Background: Reports of the direct effects of volatile anesthetics on cardiac myofibrils, studied in various mammalian species but not in humans, have conflicted. To determine whether volatile anesthetics directly affect cardiac contractile proteins in humans, we examined the effects of various equianesthetic doses of halothane (0.46, 0.83, and 1.23 mM, equivalent to 0.75, 1.50, and 2.25%, respectively) and isoflurane (0.63, 1.22, and 1.93 mM, equivalent to 1.15, 2.30, and 3.50%, respectively) on the Ca 2+ sensitivity and maximal force in human skinned cardiac fibers. Methods: Left ventricular muscle strips were obtained from seven patients undergoing cardiac surgery. Sarcolemma was disrupted with EGTA (ethylene glycol bis (β-aminoethyl ether)-N,N,N',N'-tetraacetic acid), and sarcoplasmic reticulum was destroyed with EGTA plus BRlJ 58 detergent. Ca 2+ sensitivity was studied by observing the isometric tension developed by skinned fiber bundles challenged with solutions of increasing Ca 2+ concentrations expressed in pCa (where pCa=-log10[Ca 2+ ]). Maximal force was measured with a pCa 4.8 solution. Results: Both anesthetics shifted the pCa-tension curves toward higher Ca 2+ concentrations and decreased pCa for half-maximal activation in a dose-dependent and reversible fashion (from 5.71 for control to 5.56 and 5.55 for 1 MAC halothane and isoflurane, respectively) without changing the slope of this relationship (Hill coefficient). No differences between agents were observed at equianesthetic concentrations. The two agents also decreased the maximal activated tension in a dose-dependent fashion (-27 and -28% vs. control for 2 MAC halothane and isoflurane, respectively). Conclusions: The current study indicates that halothane and isoflurane decrease Ca 2+ sensitivity and maximal force in human skinned cardiac fibers at 20 o C. If these effects extend to higher temperatures, they may contribute to the negative inotropic effect of these agents