BACKGROUND: Levosimendan is a novel drug used for inotropic support in heart failure, but its efficacy in local anesthetic-induced myocardial depression is not known. Therefore, we investigated the effects of levosimendan on the negative inotropic response to ropivacaine in isolated heart preparations of guinea pigs. METHODS: Action potentials and force of contraction were studied with conventional techniques in guinea-pig papillary muscles. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dP/dtmax), coronary flow, and PR and QRS intervals were measured in isolated constant-pressure perfused, nonrecirculating Langendorff heart preparations. Single or cumulatively increasing concentrations of levosimendan and ropivacaine were used either alone or in combination. RESULTS: In isolated papillary muscle, ropivacaine reduced force of contraction in a concentration-dependent manner. Exposure to 10 μM levosimendan in the presence of 10 μM ropivacaine almost completely reversed the negative inotropic response. Sensitivity to the positive inotropic effect of levosimendan was not altered by 10 μM ropivacaine (-logEC50 [M] = 7.03 without versus 6.9 with ropivacaine, respectively). Action potential parameters were influenced only at the highest concentration. In the Langendorff heart, levosimendan significantly reversed the ropivacaine-induced reduction in heart rate, systolic pressure, coronary flow, and +dP/dtmax to baseline values. CONCLUSION: Levosimendan is an effective inotropic drug in ropivacaine-induced myocardial depression and levosimendan myocardial sensitivity, and efficacy was not affected by the local anesthetic. Our results suggest that the calcium-sensitizing action of levosimendan is effective in local anesthetic-induced cardiac depression.