A cardioselective parameter has been available for about 2 years since the development by KATUS of an immunoassay for cardiac Troponin T (TnT). The major advantages of this TnT assay are its cardiospecificity and its sensitivity. The parameters usually determined in toxicity studies in rats to detect alterations in the myocardial cells, e.g. aspartate aminotransferase (ASAT), creatinine kinase (CK) and lactate dehydrogenase (LDH), are either of low sensitivity in this species or give falsely high results as the consequence of stress or haemolysis. We therefore investigated in the present study how well Troponin T, determined with the ELISA Troponin T from Boehringer Mannheim, can detect experimentally induced myocardial lesions in rats. In order to achieve hypoxic damage of the cardiomyocytes in these experiments in rats, male Sprague-Dawley rats were given two doses of 4 mg/kg isoprenaline each (Aludrin(R) from Boehringer Ingelheim, FRG) subcutaneously. The second dose was given 7 h after the start of the experiment. Serum samples were analysed for Troponin T (TnT) levels and, for comparison, aspartate aminotransferase (ASAT), creatine kinase (CK), and lactate dehydrogenase (LDH). Histological examinations of the heart muscle were performed 24 and 96 h after the first injection. As expected, histological examinations of the isoprena line-treated animals revealed marked myofibrillic degeneration of the myocardium 24 h after the first injection. Markedly elevated serum TnT levels (up to 7.9 ng/ml) were already evident in these animals after 6 h. TnT values decreased with time, but were still statistically significant after 48 h. Of the well-established indicators for diagnosing myocardial infarction, only ASAT showed transient statistically significant increases over 24 h. The activities of CK and LDH did not show any sensitive increases during the 96-h investigation period. On examination of the animals sacrificed 96 h after induction of myocardial damage with isoprenaline, no signs of acute myocardial degeneration were found in any of the animals. They displayed marked formation of reparative fibrosis. At this time, the TnT serum levels of all animals investigated were within the range of the control animals. Data from this study show that ELISA Troponin T is useful for sensitive and specific detection of myocardial damage in the rat. In this species, which is used for both pharmacological and toxicological experiments of varying lengths, it is possible to determine cardiac damage during the in-life phase by measurement of Troponin T.
