Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart

Abstract

A B S T R A C T Since elevation of plasma concentrations of free fatty acids (FFA) increases myocardial oxygen consumption without influencing mechanical performance in normal hearts, it was the purpose of this study to determine whether FFA would modify mechanical performance at limited oxygen supply. Left coronary blood flow was reduced by gradual clamping of a shunt from the left carotid artery until moderate ventricular dilatation supervened. Left ventricular systolic pressure (LVSP), its maximal rate of rise (dP/dt) and stroke volume (SV) were unchanged or slightly reduced. The ischelmia resulted in a decrease in myocardial oxygen consumption (MV02) from 9.7±+1.1 ml/min to 7.9±0.8 ml/min, and myocardial lactate uptake was reduced or reversed to excretion. Increasing the plasma concentrations of FFA from 359±47 iAEq/l to 3688±520 /Eq/l by intravenous infusion of a triglyceride emulsion and heparin resulted in further ventricular dilatation, accompanied by increased excretion of lactate. The ventricular decompensation and enhancement of anaerobic myocardial metabolism associated with increased uptake of FFA was not related to changes in coronary flow, MV02, or LVSP. dP/dt and SV were virtually unchanged. Intravenous infusion of glucose/insulin, which lowered plasma concentrations of FFA, reversed ventricular dilatation and lactate excretion.The data support the hypothesis that high concentrations of FFA play a significant role in increasing myocardial oxygen requirement and thereby promote depression of contractility of the hypoxic heart in experimental animals.

Effects of amino acids on substrate selection, anaplerosis, and left ventricular function in the ischemic reperfused rat heart.

“…Under normal conditions, amino acids contribute little to acetyl-CoA, but, in post-ischemic myocardium, aspartate and glutamate may indirectly alter substrate selection by stimulating both pyruvate transamination and glycolysis (20). Any shift from fatty acids to carbohydrates would be beneficial because ofoxygen sparing, which has been documented in animal models (21)(22)(23) and supported by clinical observations (24)(25)(26)(27).…”

Myocardial metabolism of free fatty acids. Studies with 14C-labeled substrates in humans.

“…Since that time, many studies have assessed myocardial metabolism in vivo in animals and humans by measuring the chemical concentration of free fatty acids in the artery and coronary sinus (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). The arterial-coronary sinus chemical differences suggested that free fatty acids (fatty acids bound to albumin) were the preferred myocardial substrate in the fasting, resting state.…”

Effect of Inhibition of Lipolysis on Infarct Size After Experimental Coronary Artery Occlusion

“…After release, and return of the electrocardiogram to normal values, drug administration was initiated, and another epicardial map 2 100 ml contains: fractionated soya bean oil, 10 g; fractionated egg lecithin, 1.2 g; glycerol, 2.5 g; water added up to 100 ml. Main fatty acid components are linoleate (40%), oleate (24%), palmitate (10%), and linolenate (7%o) (12). of S-T segments was obtained.…”

“…Marked depression of myocardial contractility has been observed in oxygen-limited hearts receiving high concentrations of FFA (11,12). This has been attributed to increased oxygen demand (12), suggesting that FFA in high concentrations contribute to the myocardial cell injury. Multiple epicardial electrocardiographic measurements were performed with a cotton wick electrode, as described previously (5).…”

“…The experiments were performed in thoracotomized dogs with the left circumflex and the LAD artery perfused separately through a shunt from the left carotid artery, as previously described (12). Coronary flow rates were determined with an electromagnetic square-wave flowmeter on the shunt (Nycotron, Oslo, Norway).…”