EXPERIMENTAL CARDIOMYOPATHY AS A MODEL OF CHRONIC HEART-FAILURE

End-stage heart disease is a major health care issue and it represents one of the most costly diseases. Several experimental heart failure m odels have been developed; however, a single model is not widely accep ted as representative of clinical heart failure. The doxorubicin-induc ed cardiomyopathy model was used in the current study to address two i ssues: 1) to define a standardized dose regimen of intracoronary doxor ubicin 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 do xorubicin was infused. Hemodynamics were obtained at weeks 0, 7, and 1 2. Echocardiography was performed weekly. Right and left ventricular b iopsy specimens were examined at weeks 0 and 12. Survival after doxoru bicin-induced cardiomyopathy was 60% at week 12. The development of he art failure was demonstrated by a significant decrease in left ventric ular ejection fraction and cardiac index and a significant increase in left ventricular end-diastolic pressure and volume. The leukocyte cou nt, hemoglobin, and hematocrit decreased significantly. Histologic cha nges of both the right and left ventricular myocardial biopsy specimen s included myocellular hypertrophy, loss of myofibrillar material, and vacuolization. Intracoronary doxorubicin reliably produced an experim ental model of accelerated heart failure that developed over the cours e of 12 weeks. Echocardiographic monitoring allowed a close surveillan ce of heart failure development. This model may be useful to evaluate the efficacy of cardiomyoplasty, mechanical assist devices, transplant ation, and reduction ventriculoplasty.