title: Oxidative capacity in failing hearts.
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 31P 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 microg. kg-1. min-1 iv) caused an approximate doubling of myocardial oxygen consumption (MVO2) 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 MVO2 in normal and LVH hearts with no change in PCr/ATP. In contrast, DNP caused no increase in MVO2 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.
authors.affiliation: Department of Medicine, Cardiovascular Division, University of Minnesota Medical School, Mayo Mail Code 508, UMHC, Minneapolis, MN 55455, USA.
authors.forename: Guangrong
authors.initials: G
authors.lastname: Gong
authors.forename: Jingbo
authors.initials: J
authors.lastname: Liu
authors.forename: Peihua
authors.initials: P
authors.lastname: Liang
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Hu
authors.forename: Ko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Hou
authors.forename: Yun
authors.initials: Y
authors.lastname: Ye
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wu
authors.forename: Abdul
authors.initials: A
authors.lastname: Mansoor
authors.forename: Arthur H L
authors.initials: AH
authors.lastname: From
authors.forename: Kamil
authors.initials: K
authors.lastname: Ugurbil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bache
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation; D004195:Disease Models, Animal; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011522:Protons; D034421:Sus scrofa
chemical_list: D011522:Protons; D010725:Phosphocreatine; D000255:Adenosine Triphosphate