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.
Department of Surgery, Division of Cardiac Surgery, University of Verona, Verona, Italy. alessio.rungatscher@univr.it
Alessio
A
Rungatscher
Daniele
D
Linardi
Maddalena
M
Tessari
Tiziano
T
Menon
Giovanni Battista
GB
Luciani
Alessandro
A
Mazzucco
Giuseppe
G
Faggian
D000818:Animals; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000494:pharmacology*; D050792:Circulatory Arrest, Deep Hypothermia Induced; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006835:Hydrazones / Q000494:pharmacology*; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014662:Vasoconstrictor Agents; D000077464:Simendan; D004837:Epinephrine