Profound bioenergetic abnormalities in peri-infarct myocardial regions.
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 F(1)F(0)-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 ((31)P-magnetic resonance spectroscopy) decreased from 2.06 +/- 0.19 in normal hearts to 1.07 +/- 0.10, with decreases in alpha-, beta-, OSCP, and IF(1) 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.
Cardiovascular Division, Department of Medicine, University of Minnesota Health Science Center, Minneapolis, MN 55455, USA.
Qingsong
Q
Hu
Xiaohong
X
Wang
Joseph
J
Lee
Abdul
A
Mansoor
Jingbo
J
Liu
Lepeng
L
Zeng
Cory
C
Swingen
Ge
G
Zhang
Julia
J
Feygin
Koichi
K
Ochiai
Toni L
TL
Bransford
Arthur H L
AH
From
Robert J
RJ
Bache
Jianyi
J
Zhang
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D008026:Ligation; D009682:Magnetic Resonance Spectroscopy; D008929:Mitochondria, Heart / Q000201:enzymology / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009211:Myoglobin / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D010725:Phosphocreatine / Q000378:metabolism; D013552:Swine; D020257:Ventricular Remodeling / Q000502:physiology
D009211:Myoglobin; C055547:deoxymyoglobin; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen; D002950:Citrate (si)-Synthase; D000251:Adenosine Triphosphatases