Experimental Studies on the Occurrence of Cardiac Hypertrophy in Ischemic Heart and Its Possible Mechanisms

我们评估了反复短暂的冠状动脉闭塞是否会在遭受可逆性缺血损伤的区域引起心肌肥大。在5只意识清醒的狗中，测量了左旋冠状动脉（LCCA）灌注区域的心内膜下段长度和左心室压力。手术完全恢复后，重复167例（平均）2分钟LCCA闭塞22天。LCCA区舒张末静息段长度增加6.6% （p<0.05）。组织学检查显示，LCCA区心肌细胞大小与左冠状动脉前降支灌注区心肌细胞大小不成比例增加（18.2 mu vs. 15.4 mu, p<0.05）。在另外5只使用类似仪器的狗中，LCCA和LAD区域的心肌细胞大小相当（14.2mu对14.0mu, p=NS）。我们的结论是，反复短暂的缺血发作导致局部心肌肥厚局限于缺血区域。[^3] prazosin结合的最大结合位点密度（Bmax）在非缺血区为13.0<正负bbb6.5 （fmol/mg蛋白）（平均<正负>SD），在缺血区为14.6<正负bbb9.5 （fmol/mg蛋白）。非缺血区解离常数（K_D）为0.17<正负>0.13 (nM)，缺血区为0.17<正负>0.17 （nM）。这两个参数无显著差异。二氢别丙诺尔在非缺血区域的Bmax为72.2<正负>5.5 （fmol/mg蛋白），K_<D'> 1.00<正负>0.25 (nM)，与缺血区域的Bmax为76.8<正负b> 25.8 （fmol/mg蛋白），K_<D:> 1.43<正负>0.75 （nM）差异不显著。[^3H] (+) PN200-100在非缺血区结合的Bmax、250<正负>26 （fmol/mg蛋白）和K_<D'> 0.24<正负>0.03 （nM）也与缺血区175<正负>9 （fmol/mg蛋白）和0.03<正负>0.14 （nM）差异不显著。这些结果表明，反复闭塞导致心肌肥大的机制似乎不涉及肾上腺素能α 1和β，以及钙通道药物结合受体的定量和定性变化。少

We evaluated whether repeated brief coronary occlusion induces myocardial hypertrophy in the region subjected to reversible ischemic insult. In 5 conscious dogs, a subendocardial segment length in the area perfused by the left circumflex coronary artery (LCCA) was measured along with left ventricular pressure. After complete recovery from surgery, 167 (mean) 2 min LCCA occlusions were repeated for 22 days. The resting end-diastolic segment length in the LCCA area was increased by 6.6% (p<0.05). On histologic examination, there was a disproportionate increase in myocardial cell size in the LCCA area compared with the area perfused by the left anterior descending coronary artery (LAD) (18.2 mu vs. 15.4 mu, p<0.05). In an additional similarly instrumented 5 dogs, myocardial cell size in the LCCA and LAD areas was comparable (14.2mu vs. 14.0mu, p=NS). We conclude that the repeated brief ischemic episodes induced regional myocardial hypertrophy confined to the ischemic area.The maximal bind … More ing site density (Bmax) for [^3] prazosin binding was 13.0<plus-minus>6.5 (fmol/mg protein) (mean <plus-minus>SD) in the nonischemic area and 14.6<plus-minus>9.5 (fmol/mg protein) in the ischemic area. The dissociation constant (K_D) was 0.17<plus-minus>0.13 (nM) in the nonischemic area and 0.17<plus-minus>0.17 (nM) in the ischemic area. Both the parameters were not significantly different. The Bmax, 72.2<plus-minus>35.5 (fmol/mg protein) and the K_<D'> 1.00<plus-minus>0.25 (nM) for H dihydroalloprenolol binding, in the nonischemic area were not significantly different from those (Bmax : 76.8<plus-minus>25.8 (fmol/mg protein), K_<D:> 1.43<plus-minus>0.75 (nM) in the ischemic area, respectively. The Bmax, 250<plus-minus>126 (fmol/mg protein) and the K_<D'> 0.24<plus-minus>0.03 (nM) for [^3H] (+) PN200-100 binding in the nonischemic area were also insignificantly different from 175<plus-minus>19 (fmol/mg protein) and 0.03<plus-minus>0.14 (nM) in the ischemic area, respectively. These results suggest that the mechanism contributing to myocardial hypertrophy induced by repeated occlusion appears to involve no quantitative and qualitative changes of adrenergic alpha1 and beta, and also calcium channel drug binding receptors. Less