title: Myocardial ischemia is more important than the effects of cardiopulmonary bypass on myocardial water handling and postoperative dysfunction: a pediatric animal model.
abstract: OBJECTIVE
  Low cardiac output state is the principal cause of morbidity after surgical intervention for congenital heart disease. Myocardial ischemia-reperfusion injury, apoptosis, capillary leak syndrome, and myocardial edema are associated factors. We established a clinically relevant model to examine relationships between myocardial ischemia, edema, and cardiac dysfunction and to assess the role of the water transport proteins aquaporins.
  
  
  METHODS
  Sixteen lambs were studied. Seven were control animals not undergoing cardiopulmonary bypass, and 9 underwent bypass. Six had 90 minutes of aortic crossclamping with blood cardioplegia and moderate hypothermia. The remaining 3 underwent cardiopulmonary bypass without aortic crossclamping. Hemodynamic and biochemical data were recorded, and myocardial edema, apoptotic markers, and aquaporin expression were determined after death.
  
  
  RESULTS
  The group undergoing cardiopulmonary bypass with aortic crossclamping had a low cardiac output state, with early postoperative tachycardia, hypotension, increased serum lactate levels, and impaired tissue oxygen delivery (P < .05) compared with the group undergoing cardiopulmonary bypass without aortic crossclamping. The lambs undergoing cardiopulmonary bypass with aortic crossclamping had increased myocardial water (P < .05) compared with those not undergoing cardiopulmonary bypass and a 2-fold increase in aquaporin 1 mRNA expression (P < .05) compared with those not undergoing cardiopulmonary bypass and those undergoing cardiopulmonary bypass without aortic crossclamping.
  
  
  CONCLUSIONS
  A temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.
authors.affiliation: Kids Heart Research, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Egan
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Butler
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Cole
authors.forename: Avetis
authors.initials: A
authors.lastname: Aharonyan
authors.forename: David
authors.initials: D
authors.lastname: Baines
authors.forename: Neil
authors.initials: N
authors.lastname: Street
authors.forename: Manchula
authors.initials: M
authors.lastname: Navaratnam
authors.forename: Oliver
authors.initials: O
authors.lastname: Biecker
authors.forename: Carla
authors.initials: C
authors.lastname: Zazulak
authors.forename: Carol G
authors.initials: CG
authors.lastname: Au
authors.forename: Yee Mun
authors.initials: YM
authors.lastname: Tan
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.forename: David S
authors.initials: DS
authors.lastname: Winlaw
mesh_terms: D000818:Animals; D017209:Apoptosis; D051398:Aquaporin 1 / Q000032:analysis; D002302:Cardiac Output / Q000502:physiology; D002315:Cardiopulmonary Bypass; D005260:Female; D006439:Hemodynamics; D007022:Hypotension / Q000209:etiology; D007773:Lactates / Q000097:blood; D008297:Male; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011183:Postoperative Complications; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep; D013610:Tachycardia / Q000209:etiology; D014867:Water / Q000378:metabolism*
chemical_list: D007773:Lactates; D012333:RNA, Messenger; D014867:Water; D051398:Aquaporin 1; D010100:Oxygen