Abstract 3647: Inhibition of Myocardial Fatty Acid Oxidation Increases Ventricular Power without Increasing Myocardial Oxygen Consumption at High Cardiac Workloads: Potential for Enhancement of Athletic Performance?
Partial inhibitors of myocardial fatty acid oxidation (FAO) improve wall motion during demand-induced ischemia without increasing oxygen use (MVO2), and thus improve mechanical efficiency. The effect of inhibition of FAO on cardiac function and MVO2 at high workloads in healthy myocardium is not known. We assessed if inhibition of FAO improves left ventricular (LV) efficiency by increasing LV power without a further increase in MVO2 at high cardiac workloads. Anesthetized pigs were instrumented with a coronary artery flow probe and venous cannula for measurement of MVO2, and subjected to 5 min high cardiac workload by rapidly infusing dobutamine+atropine and aorta constriction. Pigs were either untreated or given the FAO inhibitor oxfenicine (30 mg/kg bolus + 30 mg/kg/hr) 50 min before dobutamine (n=8/group). LV volume was measured by sonomicrometry, and LV pressure-volume loop was continuously recorded. LV mechanical efficiency was calculated as LV power/LV energy expenditure in watts. Infusion of dobutamine significantly increased myocardial blood flow, MVO2, FAO and LV power ~3-fold. Oxfenicine inhibited FAO by 75%, and significantly increased glucose and lactate uptake, but had no effect on MVO2, heart rate or blood pressure. Importantly, oxfenicine increased LV power and improved LV efficiency significantly (0.37±0.05 vs. 0.26±0.05, p<0.05) during high workload (see figure⇓). Conclusion: Inhibition of myocardial FAO improved LV efficiency at a high cardiac workload by increasing LV power without effecting MVO2. This suggests the possibility that partial inhibitors of FAO could enhance performance in athletic events that are limited by cardiac pump function.