title: Postresuscitation cyclosporine treatment attenuates myocardial and cardiac mitochondrial injury in newborn piglets with asphyxia-reoxygenation.
abstract: OBJECTIVE
  Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets.
  
  
  METHODS
  After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined.
  
  
  METHODS
  Neonatal asphyxia and reoxygenation.
  
  
  METHODS
  Twenty-four newborn (1-4 days old) piglets.
  
  
  METHODS
  Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n=8/group). Sham-operated piglets (n=8) underwent no asphyxia-reoxygenation.
  
  
  RESULTS
  Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p<0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p<0.05). The improved mitochondrial function significantly correlated with cardiac output (p<0.05, Spearman rank-correlation test).
  
  
  CONCLUSIONS
  We demonstrate that the postresuscitation administration of cyclosporine attenuates myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation.
authors: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors: Richdeep S
authors: RS
authors: Gill
authors: Tze-Fun
authors: TF
authors: Lee
authors: Namdar
authors: N
authors: Manouchehri
authors: Jiang-Qin
authors: JQ
authors: Liu
authors: Gary
authors: G
authors: Lopaschuk
authors: David L
authors: DL
authors: Bigam
authors: Po-Yin
authors: PY
authors: Cheung
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000188:drug therapy* / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage*; D006321:Heart / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects; D012151:Resuscitation / Q000379:methods; D013552:Swine; D019210:Troponin I / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D019210:Troponin I; D016572:Cyclosporine