Abstract:
Along with a good antitumor effect, Doxorubicin has a systemic effect with damage to
vital organs, in particular the heart. The lack of a unified approach to dosing and the
frequency of administration of Doxorubicin in the experiment prompts the search for
an optimal model of Doxorubicin cardiomyopathy. The aim of the study was to develop
a method of serial administration of Doxorubicin in medium therapeutic doses in an
experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats
were included in the study. The control group consisted of 7 intact rats. The
experimental group consisted of 35 rats who received systemic chemotherapy with
Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st,
28th, 35th, the hearts of experimental animals were taken for morphological
examination. Histomorphometrically determined: the diameter of cardiomyocytes (in
the middle part) and the transverse diameter of their nucleus, the width of the interstitial
space (endo- and perimysia). The data of histomorphological and histomorphometric
examination of the myocardium testified that all animals of the experimental group
had a circulatory disorder in the heart muscle at the level of hemomicrocirculation.
Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During
systemic chemotherapy, the animals showed marked changes in the myocardium,
such as expansion of the endomysial zone, due to capillary congestion and edema,
in comparison with animals of the intact group. At the end of the experiment, the
animals of the experimental group retained the expansion of the endomysial zone,
mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with
damage and death of cardiomyocytes, activation of interstitial and replacement
collagen formation. The obtained morphological data indicate the development of
dilated cardiomyopathy in experimental animals. Serial intraperitoneal administration
of Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks causes morphological
changes in the myocardium of experimental animal.
