Adriamycin-induced cardiomyopathy in the dog—an appropriate model for research on partial left ventriculectomy?

Abstract

Objective: To evaluate the adriamycin-induced cardiomyopathy in the dog for research on partial left ventriculectomy (PLV). Methods: An intracoronary catheter was introduced into the left main stem via the first diagonal branch in a retrograde fashion in 6 adult FBI (Foxhound Boehringer Ingelheim) dogs weighing 30 to 35 kg. The catheter was connected to a percutaneous access port that was used for weekly adriamycin administration (10 mg over a 1-hour period for 5 times). Follow-up examinations (transthoracic echocardiography, hemodynamic parameters, cardiopulmonary status, and neurohormones) were done before, 1 week after the last adriamycin administration, and 6 weeks later. After the last measurements, all dogs were euthanized with saturated potassium chloride under general anesthesia and the hearts were excised for histologic examinations. All data were calculated as mean values and standard error of the mean. Differences were calculated by the Wilcoxon signed rank test for paired and unpaired data. p values less than 0.05 were considered significant. Results: Central venous pressure (2.2 ± 0.8 vs 5.2 ± 0.4 mm Hg, p = 0.03), mean pulmonary artery pressure (8.6 ± 1.1 vs 12.4 ± 0.5 mm Hg, p = 0.03), pulmonary wedge pressure (2.6 ± 0.9 vs 7.0 ± 0 mm Hg, p = 0.03), left ventricular endsystolic diameter (2.5 ± 0.2 vs 3.1 ± 0.4 cm, p = 0.03), and enddiastolic (4.5 ± 0.2 vs 4.9 ± 0.2 cm, p = 0.03) diameter increased significantly after adriamycin administration, whereas cardiac output (4.0 ± 0.3 vs 3.3 ± 0.1 liter/min, p = 0.03), stroke volume index (66.0 ± 7.4 vs 54.0 ± 3.9 ml/beat/m 2, p = 0.03), and ejection fraction (61.1 ± 5.1 vs 37.7 ± 5.7%, p = 0.03) decreased markedly. These changes were accompanied by a significant decline of oxygen delivery (1130 ± 170 vs 790 ± 65 ml/min, p = 0.03), which led to an enhanced oxygen extraction (0.12 ± 0.01 vs 0.24 ± 0.01, p = 0.03). Consequently, venous oxygen saturation (82.7 ± 4.1 vs 71.3 ± 2.5%, p = 0.03) decreased. Troponin I (0.02 ± 0.025 vs 1.7 ± 0.6 ng/ml, p = 0.03) and the anti-diuretic hormone (1.9 ± 0.9 vs 20.0 ± 1.9 pg/ml, p = 0.03) increased significantly after adriamycin administration. Deterioration of cardiac function continued after termination of adriamycin administration, albeit slower than during adriamycin administration. All hearts had severe histologic alterations, which were characteristic of adriamycin-induced toxicity: cytoplasmic vacuolation, myocyte degeneration, and increased fibrosis. Conclusions: The adriamycin-induced cardiomyopathy in the dog is similar to the dilated cardiomyopathy in humans and may be an appropriate model for PLV.