In this new model of heart failure/hypertrophy, the abnormal myocardial HEP metabolism is related to the decreased CK-Mt protein level, which in turn is related to the severity of the hypertrophy.

No abstract

Although high-energy phosphate metabolism is abnormal in failing hearts [congestive heart failure (CHF)], it is unclear whether oxidative capacity is impaired. This study used the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) to determine whether reserve oxidative capacity exists during the high workload produced by catecholamine infusion in hypertrophied and failing hearts. Left ventricular hypertrophy (LVH) was produced by ascending aortic banding in 21 swine; 9 animals developed CHF. Basal myocardial phosphocreatine (PCr)/ATP measured with 31 P NMR spectroscopy was decreased in both LVH and CHF hearts (corresponding to an increase in free [ADP]), whereas ATP was decreased in hearts with CHF. Infusion of dobutamine and dopamine (each 20 g ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) caused an approximate doubling of myocardial oxygen consumption (MV O2) in all groups and decreased PCr/ATP in the normal and LVH groups. During continuing catecholamine infusion, DNP (2-8 mg/kg iv) caused further increases of MV O2 in normal and LVH hearts with no change in PCr/ATP. In contrast, DNP caused no increase in MV O2 in the failing hearts; the associated decrease of PCr/ATP suggests that DNP decreased the mitochondrial proton gradient, thereby causing ADP to increase to maintain adequate ATP synthesis. heart failure; left ventricular hypertrophy; mitochondria; high-energy phosphates; nuclear magnetic resonance IN NORMAL MYOCARDIUM, it is unclear whether peak O 2 utilization is ultimately limited by maximal oxidative ATP synthetic capacity or by the maximal capacities of the myosin and other ATPases to utilize ATP. In failing myocardium, abnormalities of excitation-contraction coupling as well as downregulation of ␤-adrenergic receptors and the downstream adenylyl cyclase system (25) make it even more difficult to determine whether ATP synthetic capacity limits contractile performance. Hence, the hypothesis that primary "energy starvation" limits function in heart failure (14) remains to be rigorously tested in vivo despite evidence that left ventricular (LV) hypertrophy (LVH) and congestive heart failure (CHF) are associated with abnormalities of myocardial energy metabolism (2,21,22,38,39).Consequently, the present study was performed to determine whether administration of a classical mitochondrial uncoupling agent [2,4-dinitrophenol (DNP)] could further increase myocardial oxygen consumption (MV O 2 ) in hearts with compensated LVH or overt cardiac failure that were already functioning at a high work state produced by catecholamine stimulation. DNP accelerates intramitochondrial metabolism proximal to ATP synthase by decreasing the proton gradient across the inner mitochondrial membrane (17,30). In response to DNP, MV O 2 increases in concert with intermediary metabolism and electron transport activity to maintain the mitochondrial proton gradient that drives ATP synthesis (15,17,30). Although it is unlikely that DNP can define the maximal oxygen utilization capacity in the intact heart (8), it can be used to determine whether there ...

These results suggest that irreversible microvascular damage to the ischemic myocardium may cause intramyocardial hemorrhage after reflow, associated with impaired recovery of left ventricular function. Contrast enhancement within the risk area shortly after reflow does not necessarily indicate long-term microvascular salvage.