In Vitro Study on Mechanisms of Bupivacaine-induced Depression of Myocardial Contractility

Although several mechanisms have been proposed to explain bupivacaine cardiotoxicity, the predominant effect remains to be determined. In this study, we used an isolated rabbit right atrial model that reproduces the effects on inotropic and chronotropic functions induced by 0.5 μg/mL bupivacaine; then we tried to counteract these events by electrical stimulation or by addition of CaCl2, or adenosine triphosphate (ATP) to the bathing solution. Contractile force was dramatically depressed by bupivacaine alone (−68%), even when the preparation was paced (−59%). CaCl2, partially counteracted this decrease (−37%). Inotropic function was almost completely restored (−9%) when ATP was added before administration of bupivacaine. Inhibition of energy metabolism seems to be a major explanation for bupivacaine cardiotoxicity.