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 sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental 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) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The 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 increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl 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 (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial 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 evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison 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 cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.
Bertinchant
J P
JP
Laboratory of Cardiovascular Physiology, University of Montpellier-Nîmes, Avenue Kennedy, 30900 Cedex, Nîmes, France. jean.pierre.bertinchant@chu-nimes.fr
Robert
E
E
Polge
A
A
Marty-Double
C
C
Fabbro-Peray
P
P
Poirey
S
S
Aya
G
G
Juan
J M
JM
Ledermann
B
B
de la Coussaye
J E
JE
Dauzat
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D009202:Cardiomyopathies / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D006331:Heart Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D007545:Isoproterenol; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D009210:Myofibrils / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
D000911:Antibodies, Monoclonal; D019210:Troponin I; D020107:Troponin T; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D007545:Isoproterenol