title: Effects of levosimendan on hemodynamics, local cerebral blood flow, neuronal injury, and neuroinflammation after asphyctic cardiac arrest in rats.
abstract: OBJECTIVE
  Despite 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.
  
  
  METHODS
  Laboratory animal study.
  
  
  METHODS
  University animal research laboratory.
  
  
  METHODS
  Sixty-one male Sprague-Dawley rats.
  
  
  METHODS
  Animals 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.
  
  
  RESULTS
  Treatment 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.
  
  
  CONCLUSIONS
  Levosimendan 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.
authors.affiliation: 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.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kelm
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wagenführer
authors.forename: Henrike
authors.initials: H
authors.lastname: Bauer
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelhard
authors.forename: Rüdiger R
authors.initials: RR
authors.lastname: Noppens
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006323:Heart Arrest / Q000188:drug therapy* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006624:Hippocampus / Q000378:metabolism; D006835:Hydrazones / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077464:Simendan
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D015850:Interleukin-6; D011724:Pyridazines; D000077464:Simendan