ABC Heart Fail Cardiomyop 2022; 2(3): 242-249
Efficacy of Different Cumulative Doses of Doxorubicin in the Induction of a Dilated Cardiomyopathy Model in Rats
Denise Mayumi Tanaka
, João Lucas O’Connell
, Camila Godoy Fabricio
, Minna Moreira Dias Romano
, Erica Carolina Campos
, Luciano Fonseca Lemos de Oliveira
, André Schmidt
, Eduardo Elias Vieira de Carvalho
, Marcus Vinícius Simões
Abstract
Background:
Doxorubicin (DOXO) has been used to induce dilated cardiomyopathy (DCM) in experimental models.
Objective:
To analyze cardiac changes after DOXO infusion and define the most effective protocol to reproduce an experimental model of DCM.
Methods:
Male Wistar rats were divided into 4 groups and received increasing cumulative doses of DOXO (at a rate of 2 mg/kg/week) or saline solution: the control group (CTR) received saline solution, Group D-8 received a total infusion of 8 mg/kg, Group D-12 received 12 mg/kg, and Group D-16 received 6 mg/kg. All animals underwent echocardiography at baseline and after the end of infusion. The animals were then euthanized and cardiac tissue was collected for histological analysis.
Results:
Mortality rates were 20% (D-8), 30% (D-12), and 67.6% (D-16). The 8 mg/kg dose was not associated with a significant reduction in left ventricular ejection fraction (LVEF) or an increase in left ventricular end-diastolic diameter (LVEDD). There was significant LVEF impairment with 12 mg/kg and 16 mg/kg doses compared to the control (68.3±5% vs 58.4±9%, p < 0.01, for CTR-12 vs D-12; and 66.0±6% vs 47.6±15%, p < 0.01, for CTR-16 vs D-16). Histological analyses revealed a greater percentage of fibrosis in D-12 (10.6±3.3%) and D-16 (9.8±2.3%) compared to CTR (2.3±1.0%), p < 0.001.
Conclusions:
The DOXO dose of 16 mg/kg was associated with severe cardiac changes and high mortality. Thus, we propose a DOXO dose of 12 mg/kg as the most appropriate and effective for inducing DCM with an acceptable mortality rate.
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