Profound bioenergetic abnormalities in peri-infarct myocardial regions

Qingsong Hu, Xiaohong Wang, Joseph Lee, Abdul Mansoor, Jingbo Liu, Lepeng Zeng, Cory Swingen, Ge Zhang, Julia Feygin, Koichi Ochiai, Toni L. Bransford, Arthur H.L. From, Robert J. Bache, Jianyi Zhang

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50 Scopus citations

Abstract

Regions of myocardial infarct (MI) are surrounded by a border zone (BZ) of normally perfused but dysfunctional myocardium. Although systolic dysfunction has been attributed to elevated wall stress in this region, there is evidence that intrinsic abnormalities of contractile performance exist in BZ myocardium. This study examined whether decreases of high-energy phosphates (HEP) and mitochondrial F1F0-ATPase (mtATPase) subunits typical of failing myocardium exist in BZ myocardium of compensated postinfarct remodeled hearts. Eight pigs were studied 6 wk after MI was produced by ligation of the left anterior descending coronary artery (LAD) distal to the second diagonal. Animals developed compensated LV remodeling with a decrease of ejection fraction from 54.6 ± 5.4% to 31 ± 2.1% (MRI) 5 wk after LAD occlusion. The remote zone (RZ) myocardium demonstrated modest decreases of ATP and mtATPase components. In contrast, BZ myocardium demonstrated profound abnormalities with ATP levels decreased to 42% of normal, and phosphocreatine-to-ATP ratio ( 31P-magnetic resonance spectroscopy) decreased from 2.06 ± 0.19 in normal hearts to 1.07 ± 0.10, with decreases in α-, β-, OSCP, and IF1 subunits of mtATPase, especially in the subendocardium. The reduction of myocardial creatine kinase isoform protein expression was also more severe in the BZ relative to the RZ myocardium. These abnormalities were independent of a change in mitochondrial content because the mitochondrial citrate synthase protein level was not different between the BZ and RZ. This regional heterogeneity of ATP content and expression of key enzymes in ATP production suggests that energetic insufficiency in the peri-infarct region may contribute to the transition from compensated LV remodeling to congestive heart failure.

Original languageEnglish (US)
Pages (from-to)H648-H657
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number2
DOIs
StatePublished - 2006

Keywords

  • Adenosine 5′-triphosphate
  • Border zone
  • Heart failure
  • Hypertrophy
  • Metabolism

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