Comparative effects of bupivacaine and ropivacaine on intracellular calcium transients and tension in ferret ventricular muscle

Abstract

Background: Recent evidence suggests that ropivacaine exerts markedly less cardiotoxicity compared with bupivacaine; however, the mechanisms are not fully understood at the molecular level. Methods: Isolated ferret ventricular papillary muscles were microinjected with the Ca2+-binding photoprotein aequorin, and intracellular Ca2+ transients and tension were simultaneously measured during twitch in the absence and presence of bupivacaine or ropivacaine. Results: Bupivacaine and ropivacaine (10, 30, and 100 μM) reduced peak systolic [Ca2+]i and tension in a concentration-dependent manner. The effects were significantly greater for bupivacaine, particularly on tension (approximately twofold). The percentage reduction of tension was linearly correlated with that of [Ca2+] i for both anesthetics, with the slope of the relationship being ≈1.0 for ropivacaine and ≈1.3 for bupivacaine (slope difference, P < 0.05), suggesting that the cardiodepressant effect of ropivacaine results predominantly from inhibition of Ca2+ transients, whereas bupivacaine suppresses Ca2+ transients and the reaction beyond Ca2+ transients, i.e., myofibrillar activation, as well. BAY K 8644, a Ca 2+ channel opener, abolished the inhibitory effects of ropivacaine on Ca2+ transients and tension, whereas BAY K 8644 only partially inhibited the effects of bupivacaine, particularly the effects on tension. Conclusion: The cardiodepressant effect of bupivacaine is approximately twofold greater than that of ropivacaine. Bupivacaine suppresses Ca2+ transients more markedly than does ropivacaine and reduces myofibrillar activation, which may at least in part underlie the greater inhibitory effect of bupivacaine on cardiac contractions. These results suggest that ropivacaine has a more favorable profile as a local anesthetic in the clinical settings.