Key result
A multimarker strategy in rats treated with minoxidil or isoproterenol successfully detected myocardial tissue damage at 24 hours and yielded highly reproducible results across different laboratories.
A multimarker strategy effectively differentiates between cardiac hypertrophy and myocardial necrosis in preclinical rat models with high interlaboratory reproducibility.
There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.
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Kim et al. (2016) studied Cardiac toxicity. Minoxidil and isoproterenol was evaluated on Discrimination between myocardial degeneration/necrosis and cardiac hypertrophy and interlaboratory variation. A multimarker strategy in rats treated with minoxidil or isoproterenol successfully detected myocardial tissue damage at 24 hours and yielded highly reproducible results across different laboratories.
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