Effect of metabolic intervention on substrate metabolism in the human heart

Myocardial substrate uptake and utilization is dependent on substrate concentrations in blood. Thus glucose extraction increases with increased glucose and decreases with increased free fatty acid (FFA) concentration, the latter effect probably mediated by inhibition of pyruvatedehydrogenase and phosphofructokinase. Carbohydrate oxidation requires less oxygen than lipid oxidation. In a series of studies in healthy men, the effects on myocardial metabolism of procedures intended to increase carbohydrate utilization were evaluated by coronary sinus catheterization utilizing [14C]oleate to estimate extraction and oxidation of FFA. Plasma FFA lowering by nicotinic acid decreased myocardial extraction of FFA and increased that of glucose, lactate, and pyruvate with concomitant increase in myocardial respiratory quotient (RQ). The fractional oxidation of FFA remained essentially unchanged. Intravenous glucose infusion increased myocardial glucose extraction, partly as a direct effect of the increased arterial glucose concentration, but, also, secondarily to the induced decrease in plasma FFA concentration and FFA extraction. It is concluded that enzyme inhibition by accumulation of intermediary metabolites, such as citrate, is important in the regulation of carbohydrate versus lipid utilization in the heart.