Simulation of acute doxorubicin cardiomyopathy in Wistar rats

Future Physiology 2021 (Virutal) (2021) Proc Physiol Soc 47, PC12

Poster Communications: Simulation of acute doxorubicin cardiomyopathy in Wistar rats

Ekaterina Podyacheva1, Tatiana Shmakova 1, Anatolia Onopchenko1, Yana Toropova1

1 V.A. Almazov National North-West Medical Research Center, Ministry of Health of the Russian Federation, Saint-Petersburg, The Russian Federation

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In the conditions of successful anticancer treatment, complications associated with its toxic effect on healthy tissues and organs began to come to the fore. Anthracycline drugs (doxorubicin (DOX), epirubicin, idarubicin) are widely used in oncological practice to treat a wide range of solid tumors and hematological malignancy. This determines the need to search for mechanisms that implement the development of those effects of chemotherapy drugs that have not been previously encountered. To solve these problems, new models are needed that could reflect these effects. The aim of the work was to develop an optimal model of doxorubicin cardiomyopathy with fibrotic lesion and distant development of diastolic dysfunction in Wistar rats. The study was carried out on 35 male Wistar rats, weighing 393 ± 38 g. The experiments were carried out in compliance with the principles of humane treatment of animals, regulated by the requirements of the European Convention on the maintenance, feeding and care of experimental animals. Throughout the study, animals were weighed and echocardiography recorded (left ventricular internal dimension / LVID /, thickness of the anterior and posterior LV walls during diastole, the shortening fraction / FS). The administration of DOX for groups A (15 mg / kg) and C (20.4 mg / kg) was performed 6 times every other day. In group B (25 mg / kg) DOX was administered 10 times every day. The control group was injected with 1 ml of 0.9% sodium chloride solution 6 times every other day. At the time of the end of the study, under the conditions of inhalation anesthesia (isoflurane), cardiac arrest was performed using KCl solution, after which vital organs were taken. The Kruskal-Wallis test was used to assess the significance of differences. ECHO results in group A on day 13 showed a significant decrease in FS (Before – 54.5 ± 5.9%; After – 37.5 ± 5.5%; *** – p ≤ 0.001) and LVIDs (Before – 3, 1 ± 0.53 mm; After – 4.1 ± 0.37 mm; *** – p ≤ 0.001). Histological examination of the heart revealed capillary plethora in all groups, which was most pronounced in group B. Also in this group there is a partial loss of myofibrils of cardiomyocytes. In group A, there is moderate venous congestion in the liver, dilated spaces of Disse. The capillaries of the kidney medulla are dilated and full-blooded. In groups B and C, venous plethora, necrosis of hepatocytes, diffuse disturbance of the structure of the hepatic tracts, and foci of hydropic dystrophy are noted in the liver. Group B and C has venous plethora of the cortical and medulla of the kidneys, moderate tubular atrophy and necrosis of individual epithelial cells. The results obtained indicate that the model of administration with a total dose of DOX from 20 mg / kg is suitable for the assessment of acute cardiotoxicity. It can be assumed that a total dose of 15 mg / kg is suitable for the assessment of chronic cardiotoxicity. In this regard, further research will be carried out.



Where applicable, experiments conform with Society ethical requirements.

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