title: Cyclosporine treatment improves cardiac function and systemic hemodynamics during resuscitation in a newborn piglet model of asphyxia: a dose-response study.
abstract: OBJECTIVE
  Asphyxiated neonates often have myocardial depression, which is a significant cause of morbidity and mortality. Cardioprotective effects of cyclosporine have been observed in adult patients and animals with myocardial infarction. However, the cardioprotective effect of cyclosporine in neonates has not yet been studied. We hypothesize that cyclosporine will improve cardiac function and reduce myocardial injury in asphyxiated newborn piglets.
  
  
  METHODS
  Thirty-six piglets (1-4 days old, weighing 1.4-2.5 kg) were acutely instrumented for continuous monitoring of cardiac output and systemic arterial pressure. After stabilization, normocapnic alveolar hypoxia (10% to 15% oxygen) was instituted for 2 hrs followed by reoxygenation with 100% oxygen for 0.5 hrs and then 21% for 3.5 hrs. A nonasphyxiated, sham-operated group was included (n = 4) to control for effects of the surgical model. Plasma troponin and myocardial lactate concentrations were determined as well as morphologic examinations.
  
  
  METHODS
  Neonatal asphyxia and reoxygenation.
  
  
  METHODS
  Newborn (1-4 days old) piglets.
  
  
  METHODS
  Piglets were block-randomized to receive intravenous boluses of cyclosporine A (2.5, 10, or 25 mg/kg) or normal saline (control) at 5 mins of reoxygenation (n = 8/group).
  
  
  RESULTS
  Cardiac index, heart rate, systemic oxygenation, plasma troponin, and left ventricular lactate were measured. Hypoxic piglets had cardiogenic shock (cardiac output 40% to 48% of baseline), hypotension (mean arterial pressure 27-31 mm Hg), and acidosis (pH 7.04). Cyclosporine treatment caused bell-shaped improvements in cardiac output, stroke volume, and systemic oxygen delivery (p < .05 vs. controls). Plasma troponin and left ventricle lactate were higher in controls than that of 2.5 and 10 mg/kg cyclosporine-treated groups (p < .05). Although histologic features of myocardial injury were not different among groups, severe damage was observed in mitochondria of control piglets but attenuated in that of cyclosporine (10 mg/kg) treatment.
  
  
  CONCLUSIONS
  Postresuscitation administration of cyclosporine causes preservation of cardiac function and attenuates myocardial injury in newborn piglets after asphyxia-reoxygenation.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richdeep S
authors.initials: RS
authors.lastname: Gill
authors.forename: Namdar
authors.initials: N
authors.lastname: Manouchehri
authors.forename: Jiang-Qin
authors.initials: JQ
authors.lastname: Liu
authors.forename: Tze-Fun
authors.initials: TF
authors.lastname: Lee
authors.forename: Woo Jung
authors.initials: WJ
authors.lastname: Cho
authors.forename: Aducio
authors.initials: A
authors.lastname: Thiesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Churchill
authors.forename: David
authors.initials: D
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000188:drug therapy* / Q000503:physiopathology; D001784:Blood Gas Analysis; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007773:Lactates / Q000097:blood; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000648:ultrastructure; D013552:Swine; D019210:Troponin I / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D007773:Lactates; D019210:Troponin I; D016572:Cyclosporine