Regulation of fatty acid oxidation by acetyl-CoA generated from glucose utilization in isolated myocytes.

The regulation of fatty acid oxidation in isolated myocytes was examined by manipulating mitochondrial acetyl-CoA levels produced by carbohydrate and fatty acid oxidation. L-carnitine had no effect on the oxidation of [U-14C]glucose, but stimulated oxidation of [1-14C]palmitate in a concentration-dependent manner. L-carnitine (5 mM) increased palmitate oxidation by 37%. The phosphodiesterase inhibitor, enoximone (250 microM), also increased palmitate oxidation by 51%. Addition of L-carnitine to enoximone resulted in a two-fold increase of palmitate oxidation. Whereas, dichloroacetate (DCA, 1 mM), which stimulates PDH activity, decreased palmitate oxidation by 25%. Furthermore, the addition of DCA to myocytes preincubated with either L-carnitine or enoximone, had no effect on the carnitine-induced stimulation of palmitate, and reduced that of enoximone by 50%. Varied concentrations of DCA decreased the oxidation of palmitate and octanoate; but increased glucose oxidation in myocytes. The rate of efflux of acetylcarnitine was highest when pyruvate was present in the medium compared to efflux rates in presence of palmitate or palmitate plus glucose. Although the addition of L-carnitine plus enoximone resulted in a two-fold increase in palmitate oxidation, acetylcarnitine efflux was minimal under these conditions. Acetylcarnitine efflux was highest when pyruvate was present in the medium. These rates were dramatically decreased when myocytes were preincubated with enoximone, despite the stimulation of palmitate oxidation by this compound. These data suggest that: (1) fatty acid oxidation is influenced by acetyl-CoA produced from pyruvate metabolism; (2) L-carnitine may be specific for mitochondrial acetyl-CoA derived from pyruvate oxidation; and (3) it is probable that acetyl-CoA from beta-oxidation of fatty acids is directly channeled into the citric acid cycle.

Myocardial tolerance to mechanical actuation is affected by biomaterial characteristics.

Direct mechanical ventricular actuation (DMVA) uses a pressure regulated heart cup, fabricated from silicone rubber (SR) for mechanical massage of the heart. Because DMVA has demonstrated potential for long-term circulatory support, investigations are currently exploring the use of more durable materials for fabricating DMVA heart cups. This study assessed the acute effects of heart cups fabricated from SR versus polyurethane (PU) on the myocardium. Dogs (n - 18) received DMVA for 4 hr of ventricular fibrillation (VF) using either SR (n = 10) or PU (n = 8) cups. Microspheres were used to determine perfusion during sinus rhythm (control) and at 2 and 4 hr of support. After support, myocardial biopsies were assayed for high energy phosphate content. Results demonstrated that PU cups required relatively frequent adjustments in drive line parameters that were likely due to material softening during PU cup support. Both PU and SR cups achieved similar hemodynamics during 4 hr of support. Myocardial perfusion, however, demonstrated a marked hyperemia at 4 hr of PU versus SR cup support. Regional high energy phosphate content was significantly decreased in hearts supported by PU versus SR cups. These results suggest that the relatively compliant characteristics of SR materials are important for achieving effective DMVA support without injuring the myocardium.