Remppis A, Scheffold T, Greten J, Haass M, Greten T, Kübler W, Katus H A
University of Heidelberg, Germany.
J Mol Cell Cardiol. 1995 Feb;27(2):793-803. doi: 10.1016/0022-2828(95)90086-1.
The marked differences in troponin T serum concentrations observed in patients with reperfused and non-reperfused myocardial infarction may be due to a perfusion dependent wash-out of an unbound fraction of cardiac troponin T. To test the release kinetics of troponin T experimentally, the isolated rat heart (Langendorff preparation) was damaged either by the calcium paradox or by no-flow ischemia. Following membrane damage by the calcium paradox troponin T (TNT) showed the same release kinetics in the coronary effluent as the cytosolic markers creatine kinase (CK) or lactate dehydrogenase (LDH). Peak levels of troponin T (282 +/- 58 micrograms/l), CK (6754 +/- 1642 U/l), and LDH (5817 +/- 1730 U/l) occurred 5 min after onset of reperfusion with calcium containing buffers and returned to 9.9%, 1.3%, and 1% of their respective peak levels within 55 min of reperfusion. During reperfusion after no-flow ischemia different release kinetics were found for cytosolic enzymes and troponin T. After 60 min of ischemia, troponin T levels in the coronary effluent increased over the entire reperfusion period of 55 min, almost doubling the 5 min value (191%). In contrast, cardiac enzymes rapidly declined to 18% (CK) and 23% (LDH) of their respective 5 min values at the end of reperfusion. Light microscopy after reperfusion with carbon black revealed a complete and homogeneous reperfusion of Langendorff hearts after no-flow ischemia. Immunoblot analysis confirmed the release of an undegraded 39 kDa troponin T molecule, both after global ischemia and the calcium paradox. These data indicate that prolonged ischemia induces a continuous liberation of cardiac troponin T, most probably from disintegrating myofibres, whereas membrane damage leads almost exclusively to leakage of a functionally unbound troponin T pool. These findings may explain the biphasic serum concentration changes of cardiac troponin T in patients with reperfused myocardial infarction.
在再灌注和未再灌注的心肌梗死患者中观察到的肌钙蛋白T血清浓度的显著差异，可能是由于心脏肌钙蛋白T未结合部分的灌注依赖性清除。为了通过实验测试肌钙蛋白T的释放动力学，采用钙反常或无血流缺血损伤离体大鼠心脏（Langendorff制备）。在钙反常导致膜损伤后，肌钙蛋白T（TNT）在冠状动脉流出液中的释放动力学与胞质标志物肌酸激酶（CK）或乳酸脱氢酶（LDH）相同。用含钙缓冲液再灌注开始后5分钟，肌钙蛋白T（282±58微克/升）、CK（6754±1642单位/升）和LDH（5817±1730单位/升）达到峰值，并在再灌注55分钟内分别降至各自峰值水平的9.9%、1.3%和1%。在无血流缺血后的再灌注过程中，胞质酶和肌钙蛋白T的释放动力学不同。缺血60分钟后，冠状动脉流出液中的肌钙蛋白T水平在整个55分钟的再灌注期内持续升高，几乎使5分钟时的值增加一倍（191%）。相比之下，心脏酶在再灌注结束时迅速降至各自5分钟时值的18%（CK）和23%（LDH）。用炭黑再灌注后的光镜检查显示，无血流缺血后Langendorff心脏实现了完全且均匀的再灌注。免疫印迹分析证实，在全心缺血和钙反常后，均有未降解的39 kDa肌钙蛋白T分子释放。这些数据表明，长时间缺血会导致心脏肌钙蛋白T持续释放，很可能来自解体的肌纤维，而膜损伤几乎只会导致功能上未结合的肌钙蛋白T池泄漏。这些发现可能解释了再灌注心肌梗死患者心脏肌钙蛋白T血清浓度的双相变化。
