Abstract:
The cardiac tissue is the most metabolically active organ in the body, for its mass, producing approximately 6kg of ATP daily. It has a remarkable remodelling capacity in the face of haemodynamic stimuli that could be due to environmental or genetic factors of physiological or pathological nature. In this study we measured the mitochondrial energetic efficiency of hypertrophic heart cardiomyocytes taken from the LV and interventricular septum of hypertrophic heart rats (HHR) and normal heart rats (NHR). This novel genetic model of HHR has the potential to extend our understanding of the genetic and phenotypic correlations of cardiac hypertrophy without the usual confounding factors of haemodynamic stresses or metabolic deregulation. The simultaneous use of the respirometer and fluorimeter allowed us the real time measurement of respiratory flux with ATP synthesis or ROS production of permeabilized fibres without or with the presence of exogenous creatine. Relative to NHR LV there was a 44.3% decreased CI oxidative phosphorylation (OXP) capacity in HHR LV and this difference was compensated during CI and CII OXP and there is evidence of greater CII capacity in HHR LV compared to NHR LV. The supplementary enzyme assays showed no difference in CI activity between the genotypes or within the animals. Therefore it is suggested that the depressed CI-OXP could be a consequence of structural difference in CI in the HHR LV rather than a functional difference as compared to NHR LV. The HHR septum seemed to have greater OXP capacity compared to NHR septum and HHR LV and this could be attributed to a comparatively greater mitochondrial density in the NHR septa. The creatine data supported the above relationships and did not contrast without creatine assays.
