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Liedtke, A James; DeMaison, Luc; Eggleston, Alice M; Cohen, Larry M; Nellis, Stephen H
Circulation research, 1988-March, Letnik: 62, Številka: 3Journal Article
The purpose of these studies was to characterize the rates of fatty acid oxidation in reperfused myocardium and test the influence of excess fatty acids (FA) on mechanical function in the extracorporeally perfused, working swine heart model. Seventeen animals were prepared. Eight were untreated (LOW FA group; serum FA averaged 0.55 ± 0.07 μmol/ml) and nine received a constant infusion of 10% Intralipid with heparin to raise serum FA to about 1.4 ± 0.21 μmol/ml (HIGH FA group). Coronary flow in both groups was held at aerobic levels for an equilibration period of 40 minutes, acutely reduced regionally in the anterior descending circulation by 60% for 45 minutes, and acutely restored to aerobic levels for 60-minute reflow. Appreciable mechanical depression (-47 δ% from aerobic values; p<0.01) during reperfusion was noted in both groups. This was associated with modest reductions in myocardial oxygen consumption (p<0.05) and losses of total tissue carnitine stores (p at least <0.02). Reperfused myocardium showed a strong preference for and aerobic use of FA during reflow such that CO2 production from labeled palmitate exceeded preischemic levels (+89 δ% in LOW FA hearts; +111 δ% in HIGH FA hearts). This suggested relative preservation or restoration of certain elements in mitochondrial function during reflow. The findings argue for uncoupling between substrate metabolism and energy production, accelerated but useless energy drainage, or some impairment between energy transfer and function of contractile proteins as possible explanations for the persistent depression of mechanical function (stunning) during reperfusion. Excess FA affected a modest decline in mechanical efficiency at aerobic flows but was without further influence during moderate-to-severe ischemia or reflow. Stunning was not associated with significant tissue accumulations of acyl CoA or carnitine.
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in: SICRIS
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