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In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation(More)
Fetuin-A is synthesized in the liver and may be associated with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Lifestyle-induced weight loss reduces fetuin-A, but the effect of exercise alone is unknown. We determined the effect of short-term exercise training on plasma fetuin-A in 13 (50.5 ± 3.4 yr) obese adults (body mass index, 33.3 ± 0.9(More)
To examine the effects of acute altitude-induced hypoxia on the hormonal and metabolic response to ingested glucose, 8 young, healthy subjects (5 men and 3 women; age, 26 +/- 2 years; body mass index, 23.1 +/- 1.0 kg/m(2)) performed 2 randomized trials in a hypobaric chamber where a 75-g glucose solution was ingested under simulated altitude (ALT, 4300 m)(More)
The rate of cardiac fatty acid oxidation is regulated by the activity of carnitine palmitoyltransferase-I (CPT-I), which is inhibited by malonyl-CoA. We tested the hypothesis that the activity of the enzyme responsible for malonyl-CoA degradation, malonyl-CoA decarboxlyase (MCD), regulates myocardial malonyl-CoA content and the rate of fatty acid oxidation(More)
Inhibition of myocardial fatty acid oxidation can improve left ventricular (LV) mechanical efficiency by increasing LV power for a given rate of myocardial energy expenditure. This phenomenon has not been assessed at high workloads in nonischemic myocardium; therefore, we subjected in vivo pig hearts to a high workload for 5 min and assessed whether(More)
Obesity is associated with a chronic low-grade inflammatory state, insulin resistance, and endothelial dysfunction, all of which contribute to increased risk of cardiovascular disease. We hypothesized that gastric bypass would produce rapid improvements in endothelial function, reduce inflammation, and lead to a decrease in cardiovascular risk. We performed(More)
During stress, patients with coronary artery disease frequently fail to increase coronary flow and myocardial oxygen consumption (MVO(2)) in response to a greater demand for oxygen, resulting in "demand-induced" ischemia. We tested the hypothesis that dobutamine infusion with flow restriction stimulates nonoxidative glycolysis without a change in MVO(2) or(More)
OBJECTIVE Clinical trials in patients with stable angina show that drugs that partially inhibit myocardial fatty acid oxidation reduce the symptoms of demand-induced ischemia, presumably by reducing lactate production and improving regional systolic function. We tested the hypothesis that partial inhibition of fatty acid oxidation with oxfenicine (a(More)
A high rate of cardiac work increases citric acid cycle (CAC) turnover and flux through pyruvate dehydrogenase (PDH); however, the mechanisms for these effects are poorly understood. We tested the hypotheses that an increase in cardiac energy expenditure: (1) activates PDH and reduces the product/substrate ratios ([NADH]/[NAD(+)] and [acetyl-CoA]/[CoA-SH]);(More)
Recent human and animal studies have demonstrated that in severe end-stage heart failure (HF), the cardiac muscle switches to a more fetal metabolic phenotype, characterized by downregulation of free fatty acid (FFA) oxidation and an enhancement of glucose oxidation. The goal of this study was to examine myocardial substrate metabolism in a model of(More)