Differences in myocardial ischemic tolerance between 1- and 7-day-old rabbits.
Between 1 and 7 days of life, the newborn rabbit heart shifts from predominantly using carbohydrates to predominantly using fatty acids as an energy substrate. We therefore used isolated working hearts from 1- or 7-day-old rabbits to determine the effects of fatty acids on myocardial glucose use and the ability of hearts to recover following various periods of transient no-flow ischemia. One-day-old hearts were perfused via the inferior vena cava and ejected buffer through the cannulated aorta and pulmonary artery. Seven-day-old hearts were perfused via the left atrium and ejected buffer through the cannulated aorta. To measure glucose use, hearts were perfused with 11 mM [3H, 14C]glucose, 3% albumin, and 500 microU insulin/mL, in the presence or absence of 0.4 mM palmitate. In the absence of fatty acids, glycolytic rates were similar in 1- and 7-day-old hearts, whereas glucose oxidation rates were 5 times greater in 7-day-old hearts. Palmitate did not have any major effects on overall glucose use in 1-day-old hearts, but did markedly inhibit glycolysis and glucose oxidation in 7-day-old hearts. A series of hearts were also subjected to periods (25-60 min) of no-flow ischemia, followed by 30 min of aerobic reperfusion. In the absence of palmitate, 1-day-old hearts subjected to ischemic periods of up to 60 min recovered some degree of mechanical function during reperfusion, whereas 7-day-old rabbit hearts failed to recover if hearts were subjected to ischemic periods of 35 min or longer.(ABSTRACT TRUNCATED AT 250 WORDS)
Lopaschuk
G D
GD
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Spafford
M A
MA
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits
D010169:Palmitic Acids; D019308:Palmitic Acid; D005947:Glucose