Abstract 19637: Superiority of Calcium Sensitizer Over Beta-Adrenoceptor Agonist for Treatment of Myocardial Dysfunction after Deep Hypothermic Circulatory Arrest. Role of Calcium Desensitization

Abstract

BACKGROUND: Rewarming from deep hypothermic circutatory arrest (DHCA) produced a calcium desensitization by cTnI phosphorylation that results in myocardial dysfunction. This study was aimed to investigate the acute overall hemodynamic and metabolic effects of epinephrine and levosimendan on myocardial function after rewarming from deep hypothermia. METHODS AND RESULTS Forty male Wistar rats (400-500 g) underwent cardiopulmonary bypass and were cooled to a core temperature of 13°C to 15°C within 30 minutes. After 15 minutes of DHCA, they were randomly assigned to treatment with levosimendan (0.1 μg/kg/min) (n=15) or epinephrine (0.1 μg/kg/min) (n =15) or saline as control (n =10). The rewarming lasted 60 minutes. Systolic and diastolic function was evaluated at different preloads with a conductance catheter. Levosimendan produced a significantly better recovery of the slope of the left ventricular end-systolic pressure volume relationship (Ees) and preload recruitable stroke work (PRSW) than ephinephrine (as percentage of baseline respectively 85+9 vs 51+11, p=0.003 and 78+5 vs 48+8, p=0.005). Levosimendan and not ephinephrine compared to control reduced left ventricular stiffness expressed by end-diastolic pressure volume relationship (EDPVR) and improved ventricular relaxation described by Tau. Levosimendan preserved high-energy phosphates content and energy charge and reduced lactate plasma concentration. Ephinephrine (E) determined a significant cTnI phosphorylation during normothermia (N) and enhanced cTnI phosphorylation after DHCA (H/R). On the contrary levosimendan (L) prevent cTnI phosphorylation that was not different from normothermic control (Fig. 1). CONCLUSIONS: Levosimendan is more effective than epinephrine for treatment of myocardial dysfunction after DHCA. Ephinephrine has a detrimental effect on calcium desensitization that has a key role in myocardial dysfunction after rewarming from DHCA.