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Experimental cardiomyopathy as a model of chronic heart failure
H R Shah1, M Vaynblat, G Ramdev
1Department of Surgery, SUNY-Health Science Center at Brooklyn, New York 11203, USA.
Insights
This study standardized a doxorubicin-induced cardiomyopathy model in dogs to reliably create experimental heart failure. Echocardiography effectively monitored the 12-week development of heart failure, proving useful for future therapeutic evaluations.
Area of Science:
- Cardiovascular Research
- Experimental Medicine
- Toxicology
Background:
- End-stage heart disease poses a significant healthcare burden and economic cost.
- Existing experimental heart failure models lack universal acceptance for clinical relevance.
- A standardized, reproducible model is needed to study heart failure progression and test interventions.
Purpose of the Study:
- To define a standardized intracoronary doxorubicin infusion dose regimen.
- To establish a method for determining the onset and time course of heart failure.
- To validate a doxorubicin-induced cardiomyopathy model in dogs for heart failure research.
Main Methods:
- Twenty dogs received an intracoronary infusion of 1 mg/kg doxorubicin.
- Hemodynamic parameters were measured at baseline, week 7, and week 12.
- Weekly echocardiography and bi-weekly ventricular biopsies (weeks 0 and 12) were performed.
Main Results:
- Survival rate was 60% at 12 weeks post-doxorubicin infusion.
- Significant decreases in left ventricular ejection fraction and cardiac index were observed.
- Histological analysis revealed myocellular hypertrophy and myofibrillar loss, confirming cardiomyopathy.
Conclusions:
- Intracoronary doxorubicin reliably induces an accelerated experimental heart failure model in dogs over 12 weeks.
- Echocardiography provides effective surveillance for monitoring heart failure development in this model.
- This model is suitable for evaluating interventions like cardiomyoplasty, mechanical assist devices, and transplantation.
Abstract:
End-stage heart disease is a major health care issue and it represents one of the most costly diseases. Several experimental heart failure models have been developed; however, a single model is not widely accepted as representative of clinical heart failure. The doxorubicin-induced cardiomyopathy model was used in the current study to address two issues: 1) to define a standardized dose regimen of intracoronary doxorubicin infusion; and 2) to establish a method of determining the onset and time course of heart failure. Twenty dogs underwent placement of an intracoronary catheter. A total dose of 1 mg/kg of intracoronary doxorubicin was infused. Hemodynamics were obtained at weeks 0, 7, and 12. Echocardiography was performed weekly. Right and left ventricular biopsy specimens were examined at weeks 0 and 12. Survival after doxorubicin-induced cardiomyopathy was 60% at week 12. The development of heart failure was demonstrated by a significant decrease in left ventricular ejection fraction and cardiac index and a significant increase in left ventricular end-diastolic pressure and volume. The leukocyte count, hemoglobin, and hematocrit decreased significantly. Histologic changes of both the right and left ventricular myocardial biopsy specimens included myocellular hypertrophy, loss of myofibrillar material, and vacuolization. Intracoronary doxorubicin reliably produced an experimental model of accelerated heart failure that developed over the course of 12 weeks. Echocardiographic monitoring allowed a close surveillance of heart failure development. This model may be useful to evaluate the efficacy of cardiomyoplasty, mechanical assist devices, transplantation, and reduction ventriculoplasty.