Doxorubicin‐Induced Canine CHF:

  Background. The dog is the most commonly used laboratory animal for heart surgery research. It has been difficult, however, to develop a canine chronic heart failure model, particularly without associated significant tachycardia. Our objective is to utilize intracoronary doxorubicin at various doses to evaluate a chronic model of left ventricular dysfunction and develop a dose‐response relationship. Methods. In 18 dogs, we evaluated their hemodynamic function, placed an in‐dwelling intracoronary catheter, and then administered four weekly infusions of doxorubicin at 5 mg (n = 6) , 10 mg (n = 6) , or 15 mg (n = 6) . Hemodynamic measurements were taken again at 4–5 weeks after infusion, and a final measurement at 14–18 weeks. Results (See table) . In the low dose group, all six animals survived the post‐infusion period. Cardiac output changed from 2.9 ± 0.2 to 2.2 ± 0.5 . The medium dose group had a mortality of 33% (2/6 dogs), with a moderate decrease in cardiac output ( 3.1 ± 0.4 to 2.3 ± 0.3 L/min ). The high dose group had a mortality of 67% (4/6 dogs), with a dramatic decrease in cardiac output ( 3.0 ± 0.2 L/min to 1.6 ± 0.7 L/min (p < 0.05) . None of the dogs developed a significant tachycardia. Conclusion . This study reconfirms that doxorubicin, when given into the coronary arteries, induces cardiac dysfunction. It appears to be dose‐dependent, but more importantly, in doses where the LV dysfunction yields overt heart failure; the mortality over 14 weeks is significant and likely unacceptable for most chronic heart failure studies. (J Card Surg 2003; 18:301‐306)