Hu Qingsong, Wang Xiaohong, Lee Joseph, Mansoor Abdul, Liu Jingbo, Zeng Lepeng, Swingen Cory, Zhang Ge, Feygin Julia, Ochiai Koichi, Bransford Toni L, From Arthur H L, Bache Robert J, Zhang Jianyi
Cardiovascular Division, Department of Medicine, University of Minnesota Health Science Center, Minneapolis, MN 55455, USA.
Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H648-57. doi: 10.1152/ajpheart.01387.2005. Epub 2006 Mar 31.
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.
心肌梗死（MI）区域被正常灌注但功能失调的心肌组成的边缘区（BZ）所包围。尽管收缩功能障碍被认为是该区域壁应力升高所致，但有证据表明BZ心肌存在收缩性能的内在异常。本研究探讨了在心肌梗死后代偿性重塑心脏的BZ心肌中，是否存在衰竭心肌典型的高能磷酸盐（HEP）减少和线粒体F（1）F（0）-ATP酶（mtATPase）亚基减少的情况。八只猪在左前降支冠状动脉（LAD）在第二对角支远端结扎造成心肌梗死后6周接受研究。动物在LAD闭塞5周后出现代偿性左心室重塑，射血分数从54.6±5.4%降至31±2.1%（MRI）。远隔区（RZ）心肌的ATP和mtATPase成分有适度减少。相比之下，BZ心肌表现出严重异常，ATP水平降至正常的42%，磷酸肌酸与ATP的比值（（31）P磁共振波谱）从正常心脏的2.06±0.19降至1.07±0.10，mtATPase的α、β、OSCP和IF（1）亚基减少，尤其是心内膜下。与RZ心肌相比，BZ心肌中肌酸激酶同工酶蛋白表达的降低也更严重。这些异常与线粒体含量的变化无关，因为BZ和RZ之间的线粒体柠檬酸合酶蛋白水平没有差异。ATP含量和ATP生成关键酶表达的这种区域异质性表明，梗死周边区域的能量不足可能促成从代偿性左心室重塑向充血性心力衰竭的转变。
