Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts

A. J. Liedtke, B. Renstrom, S. H. Nellis, R. Subramanian, G. Woldegiorgis, A. M. Eggleston, S. K. Rasmussen, D. K. Paulson, E. Scarbrough, X. Q. Huang, C. R. Kidd

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9 Scopus citations

Abstract

The purpose of these studies was to evaluate metabolic behavior in a 4- day reperfusion model in pigs after induction of subendocardial infarction. Two groups of swine [sham and intervention (Int) groups, n = 7 and 10 hearts per group, respectively] were prepared comparably with two surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descending (LAD) circulation was partially restricted (by 60%) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 ± 0.2 ml · min-1 · g dry wt- 1) for 60 min and infused by equilibrium labeling with [U · 14C]- palmitate and [5-3H]glucose to estimate fatty acid oxidation and exogenous glucose utilization. During extracorporeal perfusion, regional myocardial shortening and oxygen consumption were comparable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a significant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by 14CO2 production was 34.00 ± 4.72 μmol · h-1 · g dry wt-1 (averaged from 30-60 min of perfusion) in sham hearts but was decreased (by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utilization may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltransferase. Reduction in fatty acid oxidation in Int hearts was attended by a modest rise (P < 0.013 compared with sham hearts) in exogenous glucose utilization but no net lactate production. These studies indicated that after subendocardial injury, mitochondrial respiration is depressed in remaining viable myocardium and is accompanied by altered metabolism with decreased rates of fatty acid utilization and oxidation and increased rates of glucose utilization. However, despite the evidence for mitochondrial dysfunction, mechanical recovery was near complete, and metabolic performance remained predominantly aerobic with near normal levels of myocardial oxygen consumption and no evidence for increased anaerobic glycolysis.

Original languageEnglish (US)
Pages (from-to)H1614-H1622
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume265
Issue number5 34-5
DOIs
StatePublished - 1993

Keywords

  • carnitine palmitoyltransferase I
  • fatty acid oxidation
  • glycolysis
  • subendocardial necrosis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Liedtke, A. J., Renstrom, B., Nellis, S. H., Subramanian, R., Woldegiorgis, G., Eggleston, A. M., Rasmussen, S. K., Paulson, D. K., Scarbrough, E., Huang, X. Q., & Kidd, C. R. (1993). Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts. American Journal of Physiology - Heart and Circulatory Physiology, 265(5 34-5), H1614-H1622. https://doi.org/10.1152/ajpheart.1993.265.5.h1614