Effect of a Calcium-Sensitizing Agent, Levosimendan, on the Postcardioplegic Inotropic Response of the Myocardium

Abstract

Myocardial contractile function after coronary artery bypass graft surgery is often depressed and may require inotropic support, particularly in patients on treatment with beta-adrenergic and Ca²⁺ blockers. In view of the increase in cytosolic Ca²⁺ during early reperfusion, use of Ca²⁺ sensitizing agents may be preferable to adrenergic agonists for enhancement of contractile function after cardioplegic arrest. The aim of this study was to assess the efficacy of the Ca²⁺ sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts after normothermic and hypothermic cardioplegic arrest in the absence and presence of Ca²⁺ and beta-blockers. Isolated perfused 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 minutes of normothermic or 180 minutes of hypothermic cardioplegic arrest, reperfused, and exposed to increasing concentrations of levosimendan (10⁻⁹ to 10⁻⁶ M). Levosimendan (10⁻⁷ to 10⁻⁶ M) has positive inotropic, chronotropic, and vasodilatory effects on normoxic perfused control hearts, as well as during reperfusion after 45 minutes of normothermic cardioplegic arrest. Similar effects were elicited in the presence of the blockers. Levosimendan had no stimulatory effect during reperfusion of hearts subjected to prior hypothermic arrest. Except for the increase in heart rate, the effects of levosimendan on functional performance during reperfusion were comparable with those of adrenaline. Levosimendan elicits a positive inotropic and chronotropic response during reperfusion of hearts after normothermic cardioplegic arrest, both in the absence and presence of Ca²⁺ and beta-adrenergic blockers.