Ca2+ sensitizer superior to catecholamine during myocardial stunning?

Background: After open-chest cardiac surgery, ventricular function remains depressed (myocardial stunning). Catecholamines (epinephrine) improve ventricular function by increasing the intracellular Ca2+ concentration. In parallel, the oxygen consumption is increased, so that the hitherto intact myocardium can be jeopardized. In the very insufficient ventricle, epinephrine can even become ineffective. Since Ca2+ sensitizers provide another therapeutic avenue, the effects of epinephrine and levosimendan on postischemic hemodynamics were investigated. Methods: After hemodynamic steady state, isolated, blood (erythrocyte-enriched Krebs-Henseleit solution) - perfused rabbit hearts were subjected to 25 min normothermic, no-flow ischemia and 20 min reperfusion. Heart rate (HR), cardiac output (CO), left ventricular pressure (LVP), coronary blood flow (CBF), and arterio-venous oxygen difference (AVDO(2)) were recorded during reperfusion and after administration of either epinephrine (n = 16; 0.03 mu mol), or tevosimendan (n = 11; 0.75 mu mol) or epinephrine plus levosimendan (n = 5). Results: Epinephrine increased HR (19%, p = 0.01) and improved hemodynamics in terms of CO (62%, p = 0.0006), stroke volume SV (46%, p = 0.02), stroke work W (158%, p = 0.01), LVPmax (58%, p = 0.0001), maximal pressure increase dP/dt(max) (140%, p = 0.0004), minimal pressure increase dP/dt(min) (104%, p = 0.0002), LVPed (-26%, p = 0.02), and increased coronary resistance CR (31%, p = 0.05). Epinephrine impaired hemodynamics in terms of AVDO(2) (+63%, p = 0.003), myocardial oxygen consumption MVO2 (+67%, p = 0.0003) and MVO2/beat (+36%, p = 0.01). External efficiency 11 was increased by 92% (p = 0.02). Levosimendan in postischemic hearts increased HR (32%, p = 0.009) and improved hemodynamics in terms of CO (85%, p = 0.01), SV (44%, p = 0.03), W (115%, p = 0.04), LVPmax (95%, p = 0.04), dP/dt(max) (133%, p = 0.009), dP/dt(min) (121%, p = 0.007), LVPed (-63%, p = 0.0006), and CR (-17%; n.s., p = 0.1). It altered hemodynamics in terms of AVDO(2) (+7.0%; n.s., p = 0.3) and MVO2 (+32%, p = 0.007) and MVO2/beat (+2.3%; n.s., p = 0.4). External efficiency was increased by 307% (p = 0.04). In five additional extremely dysfunctional rabbit hearts, epinephrine was ineffective. Additional levosimendan increased hemodynamics in terms of HR (56%; n.s., p = 0.1), CO (159%, p = 0.04), SV (89%, p = 0.03), W (588%, p = 0.02), LVPmax (168%, p = 0.03), dP/dt(max) (102%, p = 0.005), dP/dt(min) (78%, p = 0.006), LVPed (-98%, p = 0.0006), and CR (-50%, p = 0.02). It altered hemodynamics in terms of AVDO(2) (-11%; n.s., p = 0.05), MVO2 (+131%, p = 0.04) and MVO2/beat (+171%, p = 0.03). External efficiency was increased by 212% (p = 0.04). Conclusion: In contrast to epinephrine, levosimendan improves ventricular function without increasing oxygen demand, thereby considerably improving external efficiency. Even during epinephrine resistance in extremely dysfunctional hearts, levosimendan successfully improves ventricular function. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier BX A[[ rights reserved.