title: Cyclosporine treatment improves mesenteric perfusion and attenuates necrotizing enterocolitis (NEC)-like intestinal injury in asphyxiated newborn piglets during reoxygenation.
abstract: OBJECTIVE
  Asphyxia-related intestinal injury in neonates may present similar to necrotizing enterocolitis (NEC) and is partially associated with hypoxia-reoxygenation injury. Cyclosporine has been shown to reduce myocardial cell death following ischemia-reperfusion. We hypothesize that cyclosporine treatment may attenuate NEC-like intestinal injury in asphyxiated newborn piglets during reoxygenation.
  
  
  METHODS
  Twenty piglets (1-4 days old) were acutely anesthetized and instrumented for continuous monitoring of systemic hemodynamics and superior mesenteric arterial (SMA) flow. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2 h followed by reoxygenation with 100% oxygen for 0.5 h, then 21% for 3.5 h. The piglets were blindly block-randomized to receive cyclosporine (10 mg/kg) or placebo (normal saline) boluses at 5 min of reoxygenation (n = 8/group). A sham-operated group was included (n = 4) and received no hypoxia-reoxygenation. Intestinal samples were collected for tissue lactate and histological assessment (Park's criteria).
  
  
  RESULTS
  At 2 h of hypoxia, piglets had cardiogenic shock (cardiac output 45% of baseline), hypotension (mean arterial pressure 30 mmHg), acidosis (pH 7.04), and decreased superior mesenteric perfusion (all P < 0.05 vs. sham-operated group, ANOVA). Cyclosporine treatment increased SMA flow (114 ± 6 vs. 78 ± 19% of baseline of controls, respectively) with improved SMA oxygen delivery and intestinal tissue lactate (all P < 0.05). Some control piglets had NEC-like injuries including pneumatosis intestinalis, which were attenuated in cyclosporine-treated piglets (P < 0.05 vs. controls).
  
  
  CONCLUSIONS
  This is the first study to demonstrate that post-resuscitation administration of cyclosporine improves mesenteric perfusion and attenuates NEC-like intestinal injury in newborn piglets following asphyxia-reoxygenation.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, AB, Canada.
authors.forename: Richdeep S
authors.initials: RS
authors.lastname: Gill
authors.forename: Namdar
authors.initials: N
authors.lastname: Manouchehri
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 L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000416:Alberta; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000188:drug therapy*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007422:Intestines / Q000187:drug effects / Q000293:injuries; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology; D012151:Resuscitation / Q000379:methods; D013552:Swine
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine