title: Intracellular compartmentation of troponin T: release kinetics after global ischemia and calcium paradox in the isolated perfused rat heart.
abstract: 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.
authors.affiliation: University of Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Remppis
authors.forename: T
authors.initials: T
authors.lastname: Scheffold
authors.forename: J
authors.initials: J
authors.lastname: Greten
authors.forename: M
authors.initials: M
authors.lastname: Haass
authors.forename: T
authors.initials: T
authors.lastname: Greten
authors.forename: W
authors.initials: W
authors.lastname: Kübler
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D014336:Troponin / Q000378:metabolism*; D020107:Troponin T
chemical_list: D014336:Troponin; D020107:Troponin T; D002118:Calcium