Levosimendan is superior to epinephrine in improving myocardial function after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats

Objective: To investigate effects of epinephrine and levosimendan on cardiac function after rewarming from deep hypothermia.

Methods: Forty-five 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 deep hypothermic circulatory arrest, they were randomly assigned to treatment with levosimendan (12 μg/kg; infusion of 0.2 μg · kg(-1) · min(-1)) (n = 15) or epinephrine (0.1 μg/kg; infusion of 0.1 μg · kg(-1) · min(-1)) (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, including the slope of the end-systolic pressure-volume relation (ESPVR) and end-diastolic pressure-volume relationship (EDPVR), preload recruitable stroke work, first derivative of left ventricular pressure (+dP/dt), and its relation to end-diastolic volume, as well as the time constant of left ventricular relaxation (Tau) and maximal slope of the diastolic pressure decrement (-dP/dt). Plasma lactate levels were collected.

Results: Stroke volume, ejection fraction and +dP/dt were significantly higher in the levosimendan-treated group than in the epinephrine group. The slope values of preload recruitable stroke work, ESPVR, and the relation of +dP/dt to end-diastolic volume were significantly higher, indicating a better contractility and increased systolic function. -dP/dt was significantly higher in the levosimendan group (3468 ± 320 vs 1103 ± 101 mm Hg/s; P < .01). Left ventricular stiffness expressed by EDPVR and relaxation (Tau) were significantly improved in levosimendan-treated group. Plasma lactated concentrations were lower in levosimendan group (2.03 ± 1.27 vs 4.64 ± 1.02; P < .05).

Conclusions: Levosimendan has better inotropic and lusitropic effects than epinephrine during rewarming from deep hypothermic circulatory arrest with cardiopulmonary bypass.