Abstract 197: The Calcium Sensitizer Levosimendan Improves Long-Term Neurological Outcome After Experimental Cardiac Arrest

Abstract

Introduction: Neurological disorder after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) is common in human survivors. Impaired cerebral blood flow (CBF) and myocardial dysfunction after successful CPR possibly affect neurological outcome. Levosimendan (Orion Corporation, Finland) improves myocardial function and enhances CBF after experimental CA and CPR. The present study investigated the effect of levosimendan on mortality and neurological outcome 7 d after experimental CA and CPR in rats. Methods: After governmental animal care committee approval (Koblenz, Germany) 80 male Sprague-Dawley rats (330 - 390 g) were included. In 64 animals asphyxial CA and CPR was achieved, randomized to a group with levosimendan treatment (Levo, n = 32, bolus [12 µg/kg] and infusion for 3 h [0.3 µg/min/kg]), or normal saline treatment (Vehicle, n = 32, bolus and infusion for 3 h [equivalent fluid volume]). For technical control 16 animals received surgical intervention and treatment without CA and CPR (sLevo, n = 8; sVehicle, n = 8). After 9 min of asphyxia and CA, CPR was initiated and experimental treatment was started. Survival, neurological assessment (neuro-deficit-score, NDS) and motor function were evaluated over a 7-d-observation period. Histopathological neuronal injury was assessed using HE-staining (expressed as numbers of viable neurons in cortex and hippocampal formation). Results: Survival showed no differences between the CA-groups after 7 d (Levo vs. Vehicle: 25 vs. 28 animals, p = 0.5092). All animals survived in sham-groups. NDS (Group comparison Levo vs. Vehicle: p = 0.003; day 7 of observation period: 13.4 ± 0.6 vs. 14.2 ± 1.4 [mean ± SD]) and cortical neuronal injury (Levo vs. Vehicle: 401 ± 87 vs. 343 ± 57 viable neurons, p = 0.007) were reduced in the Levo-group compared to Vehicle-group. Improved motor function was detected in animals treated with levosimendan (Group comparison Levo vs. Vehicle: p = 0.0091). Conclusion: In this model of CA and CPR treatment with levosimendan reduced cortical neuronal injury and ameliorated neurological performance after 7 d of survival. Based on previously demonstrated findings, the improvement of myocardial function and cerebral blood flow during reperfusion by levosimendan may cause this result.