Doxorubicin-induced canine CHF: advantages and disadvantages

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.

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.

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.