A Rapid Method for Quantitation of Toxic Heart Dilatation in Rats
Several methods are available for evaluating the cardiotoxic potency of anthracycline antitumor antibiotics (Doroshow et al. 1979). Although the Zbinden rat model is frequently used (Zbinden et al. 1978), it should be completed by morphological evaluation. However, electron microscopy is too expensive for drug screening. Thus, in this study the quantitation of the heart dilatation, as being a simple and rapidly detectable parameter for assessment of heart toxicity, is proposed. In rats the cardiotoxic effect of repeated i.v. doses of an anthracycline derivative of the rhodomycinone type was studied by the gravimetric determination of the post mortem filling volume of the heart (Fig. 1). In addition, the ECG changes (QRS complex) during the treatment period as well as ultrastructural signs of myocardiac damage (volume fractions of mitochondria, of normal and damaged myofibrils and of perimitochondrial edema) were detected. The results show a close correlation of the alteration of both the functional and the morphometric parameters. Moreover, the findings suggest that the post mortem intracardiac blood volume seems to be highly sensitive and a simple parameter for anthracycline induced heart dilatation in rodents.
Key wordsCardiotoxicity Postmortem intracardiac blood volume Rat Anthracycline
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