Journal
ANESTHESIOLOGY
Volume 96, Issue 6, Pages 1427-1434Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00000542-200206000-00023
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Background: Ropivacaine is believed to have a lower incidence of clinical cardiac side effects than bupivacaine. The aim of this study was to compare the direct cardiac effects of the optically pure S(-)-ropivacaine isomer and its nonclinically used R(+)-isomer with both optically pure bupivacaine isomers in isolated hearts. The hypothesis was that differences in direct cardiac effects are distinguished not only by stereoselective actions of local anesthetic molecules to specific receptors, but also by physicochemical. differences triggered by replacing the butyl- by a propyl-residual on pipecoloxylide. Methods: Guinea pig hearts (n = 31) were excised and perfused by the Langendorff method. Atrial and ventricular bipolar electrodes were placed to measure heart rate and atrioventricular conduction time. Left ventricular pressure, coronary flow, and oxygen tensions were measured. Twelve hearts were per-fused with increasing concentrations (0.5, 1.0, 5.0, and 10 muM) of both isomers of bupivacaine, and 13 hearts were perfused with the same concentrations of ropivacaine isomers. Six hearts were perfused with higher concentrations (20, 30, 40, and 50 muM) of both isomers of ropivacaine. The order of isomers and anesthetic chosen were randomized. Results: Both anesthetics had negative inotropic and chronotropic effects without evidence of stereoselectivity. Equal concentrations of both isomers of bupivacaine had negative inotropic effects greater than that of ropivacaine isomers. Atrioventricular conduction time was prolonged by both anesthetics in a concentration-dependent manner, but bupivacaine isomers increased atrioventricular conduction time more than ropivacaine isomers. In contrast to other variables, atrioventricular conduction time showed evident stereoselectivity for bupivacaine at the lowest concentration (0-5 muM) but only at higher concentrations for ropivacaine (> 30 muM). The R(+)isomer was more potent than the S(-)-isomer on increasing atrioventricular conduction time for both bupivacaine and ropivacaine. Conclusions: The results confirm that stereoselectivity can be demonstrated by a lengthening of atrioventricular conduction time for the more fat-soluble bupivacaine. However, for the less fat-soluble ropivacaine, the S(-)-isomer has no advantage over the R(+)-isomer for preventing slowing of atrioventricular conduction in clinical concentrations. Neither anesthetic showed stereoselective inotropic effects, but ropicavaine isomers had lesser cardiodepressant effects than bupivacaine isomers because of the replacement of the butyl- by a propyl-terminal group.
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