title: Newborn hearts are at greater 'metabolic risk' during global ischemia--advantages of continuous coronary washout.
abstract: BACKGROUND
  Altered metabolic responses of the newborn heart to ischemia, which may increase irreversible injury, may at least partially explain the greater morbidity and mortality experienced by some children undergoing congenital cardiac repair. The present study compared newborn heart metabolic responses to global ischemia with those of adult, and evaluated whether continuous coronary artery washout in the newborn heart during 'ischemia' could favourably affect these responses.
  
  
  METHODS
  Adult (n=12) and newborn (n=12) pigs were anesthetized, and right ventricular biopsies were taken before global ischemia and at set intervals during ischemia. Another 12 newborns were subdivided into groups of nonperfused hearts and hearts receiving continuous perfusion. Time to onset of and time to peak of ischemic contracture were recorded. Biopsies were assayed for lactate, myocardial glycogen, glucose-6-phosphate and ATP.
  
  
  RESULTS
  Newborn hearts were more sensitive to global ischemia than adult hearts, based on shorter time to onset of and time to peak of ischemic contracture, and had a significantly greater rate of ATP decline (P<0.01). This was due in part to a more rapid accumulation of lactate (P<0.05) and only a 50% use of glycogen, compared with 93% by adult hearts. Continuous washout of newborn hearts prevented lactate accumulation, allowing a 90% use of glycogen and delaying time to ischemic contracture by twofold. This was accompanied by lower levels of glucose-6-phosphate accumulation (P<0.05) and a threefold reduction in the rate of ATP decline.
  
  
  CONCLUSIONS
  Significant differences in myocardial metabolism during ischemia in newborns compared with adults could predispose them to earlier ischemic injury, which can be eliminated by the removal of end products. Perfusion strategies taking these differences into account may further optimize pediatric myocardial protection and improve outcomes in newborn children undergoing cardiac procedures.
authors.affiliation: Department of Surgery, University of Toronto, Ontario. c.wittnich@utoronto.ca
authors.forename: Carin
authors.initials: C
authors.lastname: Wittnich
authors.forename: Michael P
authors.initials: MP
authors.lastname: Belanger
authors.forename: Karim S
authors.initials: KS
authors.lastname: Bandali
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000378:metabolism*; D004195:Disease Models, Animal; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D019157:Ischemic Preconditioning, Myocardial / Q000009:adverse effects; D007773:Lactates / Q000378:metabolism; D015425:Myocardial Reperfusion / Q000009:adverse effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
chemical_list: D007773:Lactates; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D006003:Glycogen