Changes in oxidative phosphorylation in hearts from stressed cardiomyopathic hamsters

Stress alone is not sufficient to produce serious disease, but stress imposed upon pre-existing disease can contribute to disease progression. To demonstrate the contribution of stress to the progression of a pre-existing pathology we applied cold-immobilization stress to young (necrotic stage -2.5 month, Y) and old (hypertrophic stage - 5 month, O) cardiomyopathic hamsters (CMH), and compared them to control (CON). Mitochondrial respiration and oxidative phosphorylation were measured using polarographic techniques (Chance and Williams, 1956). The incubation medium for heart mitochondria contained 250 mM sucrose, 40 mM KCl, 1 mM KH₂PO₄, 0.5 mM EDTA, and 5 mM Hepes buffer (pH 7.4). Substrate used in experiments was 1 mM α- ketoglutarate. Our data showed that the respiration control index (RCI) was lower and state 4 respiration was higher in CMH (both Y and O) compared to CON. Stress also uncovered differences between Y and O CMH. The data showed that RCI was lower and State 4 respiration higher in Y CMH compared to O. In conclution, Y CMHs are more susceptible to stress induced changes in oxidative phosphorylation than CON and O. These data suggest that stress may differentially affect mitochondrial respiration and oxidative phosphorylation in CMHs. In addition, mitochondrial function in Y CMHs is consistent with an ischemic etiology.