FATTY-ACID OXIDATION AND MECHANICAL PERFORMANCE OF VOLUME-OVERLOADED RAT HEARTS

Chronic volume overload was induced in 2-mo-old rats by surgical opening of the aortocaval fistula. Rats were killed 3 mo later and their hearts were atrially perfused. During the perfusions with 1.2 mM palmitate, mechanical performance of volume-overloaded hearts was significantly decreased both under conditions of a moderate work load and, mainly, after the clamp of the aortic outflow line. Respective O2 consumption rates as well as the rates of (CO2)-C-14 production from [U-C-14]palmitate were decreased to the same extent. When 2.4 mM octanoate was used as the exogenous substrate, both the O2 consumption rates and the rates of CO2 production of volume-overloaded hearts became comparable to those of control hearts perfused with same substrate. Mechanical activity of volume-overloaded hearts returned to control values and remained stable during the entire perfusion period tested. Total tissue L-carnitine was decreased by approximately 30% in volume-overloaded hearts, which may suggest that palmitate oxidation has been limited at the level of carnitine-acylcarnitine translocase. However, our polargraphic studies of the respiratory activity of isolated mitochondria indicated that the palmitoylcarnitine translocation proceeds normally. On the other hand, state 3 respiration of the mitochondria from volume-overloaded hearts supplemented with either palmitate or palmitate and L-carnitine was significantly lower than that of control ones. This may suggest that an alteration of the enzymes involved in long-chain fatty acid activation and/or long-chain fatty acyl transfer to L-carnitine has developed under conditions of chronic mechanical overloading of the heart.