Willerson J T, Kulkarni P, Stone M, Lewis S E, Eigenbrodt E, Bonte F J, Parkey R W, Buja L M
Proc Natl Acad Sci U S A. 1980 Nov;77(11):6856-9. doi: 10.1073/pnas.77.11.6856.
Alterations in cell and subcellular membrane integrity occur during evolving ischemic myocardial injury. We tested the hypothesis that an antibody against human liver mitochondria [anti-mitochondrial antibody developing in a patient with primary biliary cirrhosis] could identify altered cell membrane integrity in experimental canine myocardial infarcts. The proximal left anterior descending coronary arteries of 12 dogs were ligated and 1 hr later 131I-labeled F(ab')2 fragments from either a control human IgG (6 dogs) or anti-mitochondrial IgG (6 dogs) were injected. The 131I-labeled F(ab')2 anti-mitochondrial fragments concentrated maximally in the central infarct subendocardium [infarct-to-normal ratio of 9.2 +/- 3.5 (mean +/- SD) vs. 4.6 +/- 3.3 for control F(ab')2 IgG, P < 0.05]. There was also 1 1/2- to 2-fold greater anti-mitochondrial antibody F(ab')2 accumulation in the central infarct epicardium and the peripheral infarct subendocardium and subepicardium. Thus, an anti-mitochondrial antibody obtained from a patient with primary biliary cirrhosis concentrates in irreversibly damaged myocardium after experimental canine myocardial infarction. Presumably this occurs because of altered cell membrane integrity, which allows exposure of mitochondria to the anti-mitochondrial antibody. The F(ab')2 fragments of anti-mitochondrial antibodies labeled with suitable radionuclides should allow noninvasive scintigraphic detection of experimental acute myocardial infarcts.
在不断发展的缺血性心肌损伤过程中，细胞和亚细胞膜完整性会发生改变。我们检验了这样一个假设：一种针对人肝线粒体的抗体[在原发性胆汁性肝硬化患者体内产生的抗线粒体抗体]能够识别实验性犬心肌梗死中改变的细胞膜完整性。结扎12只犬的左冠状动脉前降支近端，1小时后，分别注射来自对照人IgG（6只犬）或抗线粒体IgG（6只犬）的131I标记的F(ab')2片段。131I标记的F(ab')2抗线粒体片段在梗死灶中央心内膜下积聚最多[梗死灶与正常组织的比值为9.2±3.5（均值±标准差），而对照F(ab')2 IgG为4.6±3.3，P<0.05]。在梗死灶中央心外膜、梗死灶周边心内膜下和心外膜下，抗线粒体抗体F(ab')2的积聚也多1.5至2倍。因此，从原发性胆汁性肝硬化患者获得的抗线粒体抗体在实验性犬心肌梗死后会在不可逆损伤的心肌中积聚。推测这是由于细胞膜完整性改变，使得线粒体暴露于抗线粒体抗体所致。用合适的放射性核素标记的抗线粒体抗体的F(ab')2片段应能实现对实验性急性心肌梗死的无创闪烁扫描检测。
