Oxidative capacity in failing hearts

Guangrong Gong, Jingbo Liu, Peihua Liang, Tao Guo, Qingsong Hu, Ko Ochiai, Mingxiao Hou, Yun Ye, Xiaoyun Wu, Abdul Mansoor, Arthur H From, Kamil Ugurbil, Robert J Bache, Jianyi Zhang

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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 μg·kg-1·min-1 iv) caused an approximate doubling of myocardial oxygen consumption (MV̇O2) 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 MV̇O2 in normal and LVH hearts with no change in PCr/ATP. In contrast, DNP caused no increase in MV̇O2 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.

Original languageEnglish (US)
Pages (from-to)H541-H548
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number2 54-2
DOIs
StatePublished - Aug 1 2003

Keywords

  • Heart failure
  • High-energy phosphates
  • Left ventricular hypertrophy
  • Mitochondria
  • Nuclear magnetic resonance

Fingerprint Dive into the research topics of 'Oxidative capacity in failing hearts'. Together they form a unique fingerprint.

Cite this