• Robert F Kelm, Jürgen Wagenführer, Henrike Bauer, Irene Schmidtmann, Kristin Engelhard, and Rüdiger R Noppens.
• 1Department of Anesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. 2Department of Neuropathology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. 3Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
• Crit. Care Med.. 2014 Jun 1;42(6):e410-9.

ObjectivesDespite advances in cardiac arrest treatment, high mortality and morbidity rates after successful cardiopulmonary resuscitation are still a major clinical relevant problem. The post cardiac arrest syndrome subsumes myocardial dysfunction, impaired microcirculation, systemic inflammatory response, and neurological impairment. The calcium-sensitizer levosimendan was able to improve myocardial function and initial resuscitation success after experimental cardiac arrest/cardiopulmonary resuscitation. We hypothesized that levosimendan exerts beneficial effects on cerebral blood flow, neuronal injury, neurological outcome, and inflammation 24 hours after experimental cardiac arrest/cardiopulmonary resuscitation.DesignLaboratory animal study.SettingUniversity animal research laboratory.SubjectsSixty-one male Sprague-Dawley rats.InterventionsAnimals underwent asphyxial cardiac arrest/cardiopulmonary resuscitation, randomized to groups with levosimendan treatment (bolus 12 µg/kg and infusion for 3 hr [0.3 µg/min/kg]) or vehicle (saline 0.9% bolus and infusion for 3 hr [equivalent fluid volume]). Cardiac index, local cerebral blood flow, and hemodynamic variables were measured for 180 minutes after cardiac arrest/cardiopulmonary resuscitation. Behavioral and neurological evaluations were conducted 24 hours after cardiac arrest/cardiopulmonary resuscitation. Furthermore, neuronal injury, expressed as Fluoro-Jade B-positive cells in the hippocampal formation, cortical and hippocampal inflammatory cytokine gene expression, and blood plasma interleukin-6 values were assessed.Measurements And Main ResultsTreatment with levosimendan reduced neuronal injury and improved neurological outcome after 24 hours of reperfusion and resulted in elevated cardiac index and local cerebral blood flow compared with vehicle after cardiac arrest/cardiopulmonary resuscitation. Mean arterial blood pressure was reduced during the early reperfusion period in the levosimendan group. Cortical and hippocampal inflammatory cytokine gene expression and blood plasma interleukin-6 levels were not influenced.ConclusionsLevosimendan increased cerebral blood flow after experimental cardiac arrest/cardiopulmonary resuscitation. This effect coincided with reduced neuronal injury and improved neurologic outcome. Findings seem to be independent of inflammatory effects because no effects by levosimendan on cerebral or systemic inflammation could be detected. In summary, levosimendan is a promising agent to improve neurological outcome after cardiac arrest/cardiopulmonary resuscitation.

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