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 14CO2 production from [U-14C]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 polarographic 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.
el Alaoui-Talibi
Z
Z
Laboratorie d'Energétique et de Cardiologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie, Dijon, France.
Landormy
S
S
Loireau
A
A
Moravec
J
J
D000818:Animals; D001810:Blood Volume; D002245:Carbon Dioxide / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D010169:Palmitic Acids; D002245:Carbon Dioxide; D019308:Palmitic Acid