Cardiac Troponin T and NT-proBNP as Biomarkers of Early Myocardial Damage in Amitriptyline-Induced Cardiovascular Toxicity in Rats

Abstract

The main objective of this study was to investigate whether cardiac troponin (cTn) and N-terminal, protein B-type natriuretic peptide (NT-proBNP) can be useful as indicators for amitriptyline cardiotoxicity which is a known drug having sublethal toxic cardiac effects. At the same time, this study looked at detecting potential histopathological changes specific to irreversible cardiac injuries in a rat model of amitriptyline cardiotoxicity. Male Wistar rats were randomly divided into 2 groups, control (saline) group and amitriptyline group (100 mg/kg body weight intraperitoneally, equivalent for lethal dose at 50%). Blood was collected 30 minutes after the administration. The cTn was measured using 3 different methods (2 methods designed for human use and a sandwich enzyme immunoassay specific for rat cTnT). The brain natriuretic peptide was measured by 2 different methods (1 for human and 1 specific for rats). Electrocardiography showed that the QRS complex ( P < .0001) and the QT interval ( P = .002) were significantly prolonged for amitriptyline-treated animals. Troponin T and NT-proBNP had significantly increased levels in all the rats but showed positive results only when using rat-specific quantitative measurement. In certain rats, the histopathological examination identified a few small foci of acute myocardial necrosis. In conclusion, elevation of cTnT and NT-proBNP are early indicators of cardiotoxicity, yet the significance of irreversible myocardial damage in amitriptyline cardiotoxicity needs to be further understood.