Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensit ive and specific markers of myocardial cell injury. The purpose of this stu dy was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whethe r they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnI and cTnT release with histological e xaminations, using isoprenaline-induced cardiac muscle damage as an experim ental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access(R)) and cTnT (Elecsys(R)) assays cross-react with cTnI and cT nT of the rat, A highly significant rise of cTnI or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. T he highest cTnI (mean +/- S.D., 1.1 +/- 2.3 ng/ml) and cTnT (mean +/- S.D. 3.6 +/- 30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly inc reased in iso-treated rats in comparison with controls whether the differen ces between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnI and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (exc ept a trend for LD whether or not the difference between 6-h levels and bas al levels were considered (P = 0.08) and for LD AUC (0-6 h) (P = 0.059)). C orrelations between maximal cTnI and cTnT and AUC were 0.69 (P = 0.0001) an d 0.60 (P = 0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the m yocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evide nce of mild changes and slight mononuclear cell infiltration. cTnI and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary t o detect histological myocardial cell injury after iso. cTnI and cTnT were Found to be early markers for diagnosing iso;induced myocardial damage in c omparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cro ss-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT ca n be used as easily measurable target parameters for detection of cardiotox ic and/or cardiodegenerative effects in rats. (C) 2000 Elsevier Science B.V . All rights reserved.