The Assessment of Cardiac Biomarkers in Rat Models of Cardiotoxicity

Cardiotoxicity is an adverse effect of many drugs and chemicals. However, the assessment of toxic myocardial injury in preclinical animal studies for drug safety evaluation has not been optimised. At present, cardiac injury is generally assessed using serum enzymes and these changes are correlated with histopathological lesions in the heart. Nevertheless, it has recently been suggested that the assessment of cardiac injury using serum enzymes as biomarkers lacks sensitivity and it has therefore been proposed that new markers should be identified and validated; a proposed new serum marker is cardiac troponin I (cTnI). The aim of the present investigations was to develop models of cardiotoxicity in the Hanover Wistar rat using isoproterenol (ISO), allylamine (AA) and erucic acid (EA), to assess the usefulness of serum cTnI in comparison with the traditional markers of myocardial injury. Single dose studies with ISO and AA resulted in myocardial degeneration/necrosis, and vasculopathy was also present in the case of AA. These experiments demonstrated that serum cTnI was a sensitive and specific biomarker of acute cardiomyocyte injury. Administration of EA, by gavage or in the diet, induced myocardial lipidosis and necrosis. Serum levels of cTnI were generally elevated in association with myocardial necrosis, but not with lipidosis. It is concluded that cTnI is a sensitive and organ-specific marker of cardiotoxicity in the rat, but further validation studies are required with a wider range of cardiotoxic agents