Effect of a calcium-sensitizing agent, levosimendan, on the postcardioplegic inotropic response of the myocardium

Myocardial contractile function after coronary artery bypass graft surgery is often depressed and may require inotropic support, particularly in patie nts on treatment with beta-adrenergic and Ca2+ blockers. In view of the inc rease in cytosolic Ca2+ during early reperfusion, use of Ca2+ sensitizing a gents may be preferable to adrenergic agonists for enhancement of contracti le function after cardioplegic arrest. The aim of this study was to assess the efficacy of the Ca2+ sensitizer, levosimendan, as an inotrope on the me chanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca2+ and beta-blockers. Isolated per fused working guinea pig hearts were perfused in the absence or presence of propranolol (10(-6) M) and/or nifedipine (10(-8) M), subjected to 45 minut es of normothermic or 180 minutes of hypothermic cardioplegic arrest, reper fused, and exposed to increasing concentrations of levosimendan (10(-9) to 10(-6) M). Levosimendan (10(-7) to 10(-6) M) has positive inotropic, chrono tropic, and vasodilatory effects on normoxic perfused control hearts, as we ll as during reperfusion after 45 minutes of normothermic cardioplegic arre st. Similar effects were elicited in the presence of the blockers. Levosime ndan had no stimulatory effect during reperfusion of hearts subjected to pr ior hypothermic arrest. Except for the increase in heart rate, the effects of levosimendan on functional performance during reperfusion were comparabl e with those of adrenaline. Levosimendan elicits a positive inotropic and c hronotropic response during reperfusion of hearts after normothermic cardio plegic arrest, both in the absence and presence of Ca2+ and beta-adrenergic blockers.