Heart mitochondrial abnormalities in a canine model of pacing‐induced heart failure

Bioenergetic failure may contribute to the evolution of heart failure, but the molecular basis of the mitochondrial defect is still unknown. Abnormalities in the enzymatic activity of the electron transport chain (ETC) complexes have been reported in heart failure of different etiology in humans and animal models. We hypothesized that mitochondrial dysfunction precedes the inotropic abnormalities of two cardiac contractile areas (septal and lateral wall) in a canine model of pacing‐induced heart failure. Cardiac subsarcolemmal (SSM) and intermyofibrillar (IFM) mitochondria isolated from both septal and lateral wall were evaluated for the function of substrate oxidation coupled to ATP synthesis (oxidative phosphorylation), and the enzymatic activity of the ETC complexes. We found an early and specific defect of the mitochondrial complex III in both SSM isolated from the septum and IFM isolated from the lateral wall. Our data suggest a common mechanism responsible for the dysfunction of different cardiac mitochondrial populations in heart failure. Since IFM are mostly responsible for the generation of the ATP necessary for contractile apparatus, the bioenergetic failure of the lateral wall might be the primary phenomenon during the evolution of heart failure. Supported by NIH grants to CLH.