Effect of congestive heart failure on the intrinsic metabolic capacity of the liver in the dog.
The intrinsic metabolic capacity of the liver at end-stage heart failure in the pacing overdrive dog model of congestive heart failure was evaluated ex vivo. Congestive heart failure was induced in seven adult mongrel dogs (20-30 kg) by cardiac electrical pacing at a frequency of 240 stimuli/min until the development of overt heart failure; seven other dogs served as controls. The animals were then anesthetized and the right ventricular papillary muscles and samples from the left lateral hepatic lobes were collected. The degree of myocardial dysfunction as well as the total amount and the activities of cytochromes P-450 were evaluated. Tension, maximum rate of tension rise, and Vmax were significantly lower (40-60%) in the paced than in the control dogs, indicating a marked myocardial dysfunction. Moreover, significant decreases in total cytochrome P-450 (0.31 +/- 0.04 vs. 0.53 +/- 0.03 nmol/mg of microsomal protein, p less than 0.01) and in the intensity of four different electrophoretic protein bands (molecular masses of 46, 48, 50, and 59 kDa) occurred in the dogs with congestive heart failure. The decrease in total cytochrome P-450 was accompanied by a significant reduction in aminopyrine N-demethylase activity (1.74 +/- 0.25 vs. 2.91 +/- 0.40 nmol/min/mg of microsomal protein, p less than 0.05). Immunoblot analysis using antibodies to two different dog liver phenobarbital-inducible cytochromes P-450 demonstrated that PBD-1 (a P-450IIIA) was not affected by congestive heart failure, whereas PBD-2 (a P-450IIB) was markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)
Hôpital du Sacré-Coeur de Montréal, Department of Pharmacology, Université de Montréal, Québec, Canada.
C
C
Lambert
J R
JR
Halpert
J
J
Rouleau
L
L
Jutras
V
V
Leroyer
P
P
du Souich
D000818:Animals; D001696:Biomechanical Phenomena; D001711:Biotransformation / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004790:Enzyme Induction / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism*; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010210:Papillary Muscles / Q000503:physiopathology; D010634:Phenobarbital / Q000494:pharmacology
D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital