Effects of L-propionylcarnitine on mechanical recovery during reflow in intact hearts

International audienc

Changes in substrate metabolism and effects of excess fatty acids in reperfused myocardium

International audienc

Changes in energy metabolism and mitochondrial function in the reperfused working swine heart

International audienc

Effects of (+)-octanoilcarnitine in intact myocardium

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Effects of (+)-octanoylcarnitine in intact myocardium

International audienceFatty acid metabolites (long-chain esters of CoA and carnitine) which collect in ischemic myocardium can form amphiphiles capable of disrupting subcellular performance. It is important to document the role of these amphiphiles in intact tissue. D-Octanoylcarnitine was chosen because of its previously described effects on inhibiting palmitoylcarnitine transferasc (PCT-II) inin vitro andin vivo liver preparations. This inhibition will shift tissue levels of CoA and carnitine intermediates and thus alter amphiphile levels. The compound's actions in cardiac muscle are unknown. Dose response curves were developed in intact hearts to test the influence of D-octanoylcarnitine at pharmacological concentrations. Measurements were obtained in working, extracorporeally perfused, swine hearts. Drug was administered either systemically (IV) or via dircct intracoronary (IC) infusions into the left anterior descending coronary circulation. Excess fatty acids were provided to ensure adequate fatty acid substrate for oxidation. Coronary flow was controlled at aerobic levels. Systemic administration of D-octanoylcarnitine (0.8–6.8 mM) resulted in transient peripheral hypotension which caused correlative decreascs in14CO2 production from labeled palmitate. Infusion of D-octanoylcarnitine (0.5–3.9 mM) IC did not cause appreciable hypotension and was not associated with suppression of fatty acid oxidation. No build-up of carnitine esters was noted in treated hearts but acyl CoA levels were reduced (p<-0.002). this="" latter="" finding="" was="" modestly="" related="" to="" increasing="" dose="" schedule="" of="" the="" compound="" in="" the="" ic="" group.="" the="" lack="" of="" suppression="" in="" fatty="" acid="" oxidation="" argues="" against="" significant="" inhibition="" of="" pct="" ii="" and="" lessens="" the="" attractiveness="" of="" using="" d-octanoylcarnitine="" in="" intact="" myocardium="" to="" selectively="" bloock="" fatty="" acid="" utilization="" at="" this=""