title: Effects of post-resuscitation treatment with N-acetylcysteine on cardiac recovery in hypoxic newborn piglets.
abstract: OBJECTIVE
  Although N-acetylcysteine (NAC) can decrease reactive oxygen species and improve myocardial recovery after ischemia/hypoxia in various acute animal models, little is known regarding its long-term effect in neonatal subjects. We investigated whether NAC provides prolonged protective effect on hemodynamics and oxidative stress using a surviving swine model of neonatal asphyxia.
  
  
  RESULTS
  Newborn piglets were anesthetized and acutely instrumented for measurement of systemic hemodynamics and oxygen transport. Animals were block-randomized into a sham-operated group (without hypoxia-reoxygenation [H-R, n = 6]) and two H-R groups (2 h normocapnic alveolar hypoxia followed by 48 h reoxygenation, n = 8/group). All piglets were acidotic and in cardiogenic shock after hypoxia. At 5 min after reoxygenation, piglets were given either saline or NAC (intravenous 150 mg/kg bolus + 20 mg/kg/h infusion) via for 24 h in a blinded, randomized fashion. Both cardiac index and stroke volume of H-R controls remained lower than the pre-hypoxic values throughout recovery. Treating the piglets with NAC significantly improved cardiac index, stroke volume and systemic oxygen delivery to levels not different from those of sham-operated piglets. Accompanied with the hemodynamic improvement, NAC-treated piglets had significantly lower plasma cardiac troponin-I, myocardial lipid hydroperoxides, activated caspase-3 and lactate levels (vs. H-R controls). The change in cardiac index after H-R correlated with myocardial lipid hydroperoxides, caspase-3 and lactate levels (all p<0.05).
  
  
  CONCLUSIONS
  Post-resuscitation administration of NAC reduces myocardial oxidative stress and caused a prolonged improvement in cardiac function and in newborn piglets with H-R insults.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jiang-Qin
authors.initials: JQ
authors.lastname: Liu
authors.forename: Tze-Fun
authors.initials: TF
authors.lastname: Lee
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3 / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D006861:Hydrogen Peroxide / Q000737:chemistry; D000860:Hypoxia; D007773:Lactates / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry / Q000627:therapeutic use; D010102:Oxygen Inhalation Therapy / Q000379:methods; D017382:Reactive Oxygen Species; D013318:Stroke Volume; D013552:Swine; D019210:Troponin I / Q000378:metabolism
chemical_list: D007773:Lactates; D008055:Lipids; D017382:Reactive Oxygen Species; D019210:Troponin I; D006861:Hydrogen Peroxide; D053148:Caspase 3; D010100:Oxygen; D000111:Acetylcysteine