INTRACELLULAR COMPARTMENTATION OF TROPONIN-T - RELEASE KINETICS AFTERGLOBAL-ISCHEMIA AND CALCIUM PARADOX IN THE ISOLATED-PERFUSED RAT-HEART

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 car diac troponin T. To test the release kinetics of troponin T experiment ally, the isolated rat heart (Langendorff preparation) was damaged eit her 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 k inase (CK) or lactate dehydrogenase (LDH). Peak levels of troponin T(2 82 +/- 58 mu g/l), CK (6754 +/- 1642 U/l), and LDH (5817 +/- 1730 U/l) occurred 5 min after onset of reperfusion with calcium containing buf fers and returned to 9.9%, 1.3%, and 1% of their respective peak level s within 55 min of reperfusion, During reperfusion after no-flow ische mia different release kinetics were found for cytosolic enzymes and tr oponin T. After 60 min of ischemia, troponin T levels in the coronary effluent increased over the entire reperfusion period of 55 min, almos t doubling the 5 min value (191%), In contrast, cardiac enzymes rapidl y declined to 18% (CK) and 23% (LDH) of their respective 5 min values at the end of reperfusion. Light microscopy after reperfusion with car bon black revealed a complete and homogenous reperfusion of Langendorf f hearts after no-flow ischemia, Immunoblot analysis confirmed the rel ease of an undegraded 39 kDa troponin T molecule, both after global is chemia and the calcium paradox.These data indicate that prolonged isch emia induces a continuous liberation of cardiac troponin T, most proba bly from disintegrating myofibres, whereas membrane damage leads almos t exclusively to leakage of a functionally unbound troponin T pool. Th ese findings may explain the biphasic serum concentration changes of c ardiac troponin T in patients with reperfused myocardial infarction.