What is the clinical evidence from this study?

Study design: Other. Population: Dilated Cardiomyopathy (n=86). Intervention: Doxorubicin vs. Saline solution. Primary outcome: Left ventricular ejection fraction (LVEF) (p=<0.01).

January 1, 2022Open Access

Efficacy of Different Cumulative Doses of Doxorubicin in the Induction of a Dilated Cardiomyopathy Model in Rats

Q: What are the key findings of this study?

A cumulative doxorubicin dose of 12 mg/kg significantly reduced left ventricular ejection fraction compared to control (58.4% vs 68.3%) and induced myocardial fibrosis with an acceptable 30% mortality rate.

Key Result

A cumulative doxorubicin dose of 12 mg/kg significantly reduced left ventricular ejection fraction compared to control (58.4% vs 68.3%) and induced myocardial fibrosis with an acceptable 30% mortality rate.

Structured PICO

What is the most effective cumulative dose of doxorubicin to induce a dilated cardiomyopathy model in male Wistar rats?

Population

86 adult male Wistar rats randomized to receive varying cumulative doses of doxorubicin or saline to establish an optimal experimental model of dilated cardiomyopathy.

Intervention

Doxorubicin (DOXO) infusion at a rate of 2 mg/kg/week (cumulative doses including 8 mg/kg and 12 mg/kg)

Comparator

Saline solution

Outcome

Cardiac changes to define the most effective protocol to reproduce an experimental model of dilated cardiomyopathysurrogate

This study aims to define the optimal cumulative dose of doxorubicin to induce a dilated cardiomyopathy model in rats.

Main Result

Absolute Event Rate: 58.4% vs 68.3%

p-value: p=<0.01

Limitations

High mortality (67.6%) associated with the 16 mg/kg cumulative dose limits its utility.
Potential dissociation between the degree of tissue injury and the intensity of left ventricular dysfunction at higher doses.
Systemic toxicity (renal, bone marrow, gastrointestinal) contributes to weight loss and mortality, complicating the heart failure model.

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 ...

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