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1 Medicine/Cardiovascular Division, Unitversity of Minnesota, Minneapolis, Minnesota, United States
2 Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, United States
3 Radiology, University of Minnesota, Minnesota, Minnesota, United States
* To whom correspondence should be addressed. E-mail: zhang047{at}umn.edu.
Regions of myocardial infarct 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 and mitochondrial F1F0-ATPase (mtATPase) subunits typical of failing myocardium exist in BZ myocardium of compensated post-infarct remodeled hearts. Eight pigs were studied 6 weeks after MI was produced by ligation of the left anterior descending coronary artery (LAD) distal to the 2nd diagonal . Animals developed compensated LV remodeling with a decrease of ejection fraction from 54.6±5.4% to 31±2.1% (MRI) 5 weeks after LAD occlusion. The remote 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 (PCr)/ATP (31P- MRS) decreased from 2.06±0.19 in normal hearts to 1.07±0.10, with decreases in 
, 
, OSCP and IF1 subunits of mtATPase, especially in the subendocardium. The reduction of myocardial CK isoform protein expression was also more severe in the BZ relative to the RZ. These abnormalities were independent of a change in mitochondrial content since 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.
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