Mitochondrial ATPase and high-energy phosphates in failing hearts

This study examined high-energy phosphates (HEP) and mitochondrial ATPase p rotein expression in hearts in which myocardial infarction resulted in eith er compensated left ventricular remodeling (LVR) or congestive heart failur e (CHF). The response of HEP (measured via P-31 magnetic resonance spectros copy) to a modest increase in the cardiac work state produced by dobutamine -dopamine infusion and pacing (if needed) was examined in 17 pigs after lef t circumflex coronary artery ligation (9 with LVR and 8 with CHF) and compa red with 7 normal pigs. In hearts with LVR, the baseline phosphocreatine (P Cr)-to-ATP ratio decreased, and calculated ADP increased; these changes wer e most severe in hearts with CHIP. HEP levels did not change in normal or L VR hearts during dobutamine-dopamine infusion. However, in hearts with CHIP , the PCr-to-ATP ratio decreased further, and free ADP increased. The mitoc hondrial protein levels of the F0F1-ATPase subunits were normal in hearts w ith compensated LVR. However, in failing hearts, the a-subunit decreased by 36%, the beta -subunit decreased by 16%, the oligomycin sensitivity-confer ring protein subunit decreased by 40%, and the initiation factor 1 subunit decreased by 41%. Thus in failing hearts, reductions in mitochondrial F0F1- ATPase protein expression are associated with increased myocardial free ADP .