Comparative Effects of Bupivacaine and Ropivacaine on Intracellular Calcium Transients and Tension in Ferret Ventricular Muscle

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 [mu]m) 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 [almost equal to]1.0 for ropivacaine and [almost equal to]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 Ca2+ 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.