title: Studies of myocardial protection in the immature heart. III. Models of ischemic and hypoxic/ischemic injury in the immature puppy heart.
abstract: This study compares the metabolic and functional effects of three different models of ischemia in the immature heart. The intent was (1) to develop a model of energy-depleted and functionally depressed heart to be used in subsequent studies of myocardial protection and (2) to characterize the biochemical changes following different interventions. Forty-five minutes of normothermic global ischemia produced severe depletion of adenosine triphosphate and creatine phosphate (greater than 70%) but was associated with 85% +/- 10% recovery of left ventricular function. Postischemic functional depression (less than 30% recovery) could be produced by either (1) extending the ischemic duration to 60 minutes or (2) preceding 45 minutes of ischemia by 60 minutes of hypoxic stress (oxygen tension 25 to 30 mm Hg). Neither of these more severe interventions caused more profound depletion of adenosine triphosphate or creatine phosphate, but hypoxic stress produced marked tissue depletion of glutamate (52%) and aspartate (48%) before aortic clamping. Longer ischemia or preceding hypoxia led to greater myocardial accumulation of lactate (greater than 250 versus 104 mumol/gm dry weight) and succinate (18 versus 11 mumol/gm dry weight) during aortic clamping, p less than 0.05 versus 45 minutes of ischemia) and greater postischemic depression and amino acid (greater than 65% aspartate depletion) and carbohydrate (greater than 50% glycogen depletion) metabolism, p less than 0.05 versus simple ischemia. These findings suggest that more severe ischemic/hypoxic models are needed in immature hearts to produce functional depression, and the biochemical analyses suggest the characteristics of metabolic defects that must be corrected to resuscitate these hearts during surgical correction of congenital defects.
authors.affiliation: UCLA Medical Center, Department of Surgery 90024.
authors.forename: P
authors.initials: P
authors.lastname: Julia
authors.forename: E R
authors.initials: ER
authors.lastname: Kofsky
authors.forename: G D
authors.initials: GD
authors.lastname: Buckberg
authors.forename: H H
authors.initials: HH
authors.lastname: Young
authors.forename: H I
authors.initials: HI
authors.lastname: Bugyi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000600:Amino Acids, Dicarboxylic / Q000378:metabolism; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D000600:Amino Acids, Dicarboxylic; D002264:Carboxylic Acids; D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen