A canine model of heart failure by intracoronary adriamycin injection: hemodynamic and energetic results

Background: To eliminate the noncardiac toxicities associated with Adriamycin (Pharmacia Upjohn, Kalamazoo, MI) and to avoid the need for surgical implantation of a coronary artery catheter, we proposed serial intracoronary infusions of Adriamycin (Pharmacia Upjohn) with a Judkins catheter to develop a nonsurgical but selective model of dilated cardiomyopathy in dogs. Methods and Results: Twenty-two dogs were entered onto the study. Each dog received four weekly injections of Adriamycin (Pharmacia Upjohn; 15 mg/wk) through a Judkins catheter and verapamil orally (5 mg/kg twice daily) for 4 weeks. Dogs were evaluated with echocardiography, right-sided cardiac catheterization, and endomyocardial biopsy at times 0 and 10 weeks. The left ventricular ejection fraction decreased from 0.65 ± 0.04 to 0.48 ± 0.11 (P = .0006). The left ventricular end-diastolic and end-systolic diameter indices increased from 42.00 ± 2.17 to 46.92 ± 5.81 mm (P = .0029) and from 27.65 ± 2.59 to 35.00 ± 6.84 mm, respectively (P = .0210). The mechanical cardiac efficiency decreased from 28.55% ± 13.30% at baseline and 15.64% ± 9.09% at 10 weeks (P = .001). Cardiac myocyte vacuolation was present on histological examination at 10 weeks. The mortality rate was 41%. Minimal systemic Adriamycin (Pharmacia Upjohn) toxicity was noticed. Conclusion: Intracoronary injection of Adriamycin (Pharmacia Upjohn) in dogs induced a chronic dilated cardiomyopathy.