Background: Clinical methods for the early detection of doxorubicine (adriamycin; ADR) -induced cardiotoxicity have not been established. This study prospectively investigated whether atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cardiac troponin T (TnT) are predictors for ADR-induced cardiotoxicity, and examined the correlations between the serum concentrations of these biomarkers and the functional alternations associated with ADR-induced myocardial damage.
Methods and results: Male Wistar rats were injected weekly with 2 mg/kg of ADR via the tail vein for 8 weeks to induce cardiotoxicity. Echocardiograms of each ether anesthetized rat were taken at 6, 8, 10 and 12 weeks after the first administration of ADR, and blood samples collected from the tail vein were used to quantify plasma ANP and BNP, and serum TnT after echocardiography. Plasma BNP and serum TnT significantly increased from 6 to 12 weeks (81.5 to 173.3 pg/ml (p<0.001), <0.01 to 1.09 ng/ml (p<0.05), respectively) with deterioration of left ventricular % fractional shortening (%FS) (58.6% to 36.8%). The %FS significantly correlated with TnT (r=-0.51, p<0.001) and BNP (r=-0.75, p<0.0001); however, the increase of TnT was antecedent to the increase of BNP and the deterioration of %FS.
Conclusion: Plasma BNP and serum TnT concentrations, especially TnT, measured by this highly sensitive method are useful predictors for ADR-induced cardiomyopathy.