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J Thorac Cardiovasc Surg 1998;115:1367-1374
© 1998 Mosby, Inc.

CARDIOPULMONARY SUPPORT AND PHYSIOLOGY

A canine model of dilated cardiomyopathy induced by repetitive intracoronary doxorubicin administration

From the Department of Surgery, Division II, Kobe University School of Medicine, Kobe, Japan.

Received for publication July 3, 1997. Revisions requested Sept. 2, 1997; revisions received Jan. 19, 1998. Accepted for publication Jan. 21, 1998. Address for reprints: Yoshiya Toyoda, MD, Department of Surgery, Division II, Kobe University School of Medicine, 7-5-2 Kusunokicho, Chuo-ku, 650 Kobe, Japan.

Abstract

Objective: A simple and reproducible large animal model of dilated cardiomyopathy has yet to be developed. This study was performed to establish a canine model of dilated cardiomyopathy.
Methods: Six closed-chest purebred beagles weighing 8 to 12 kg (10 ± 1.9 kg) underwent intracoronary infusion of doxorubicin (Adriamycin). Low-dose (0.7 mg/kg) doxorubicin was infused into the left main coronary artery through a 5F Judkins catheter. Infusions were repeated weekly for 5 weeks. We evaluated the effects on cardiac hemodynamics, chamber size, the neuroendocrine system, and cardiac ultrastructure before and 1 and 3 months after five intracoronary infusions of doxorubicin.
Results: Three months after treatment, fractional shortening (mean ± standard error of the mean) had decreased from 36.5% ± 0.8% to 21.7% ± 1.4% (p = 0.0003), and left ventricular ejection fraction had decreased from 71.0% ± 3.3% to 36.3% ± 5.5% (p = 0.001). The left ventricular diastolic dimension had increased from 27.8 ± 0.9 to 35.5 ± 0.6 mm (p = 0.003), and the left ventricular end-diastolic volume had increased from 27.5 ± 1.8 to 38.3 ± 1.9 ml (p = 0.015). Left ventricular end-diastolic pressure had increased from 8.5 ± 0.9 to 14.5 ± 1.1 mm Hg (p = 0.01), and the stroke volume had decreased from 16.7 ± 0.9 to 11.5 ± 0.4 ml (p = 0.001). During the same period, the plasma norepinephrine concentration also increased from 114 ± 27.4 to 423 ± 88.9 pg/ml (p = 0.024), and plasma atrial natriuretic peptide levels increased from 33.8 ± 7.0 to 76.5 ± 14.8 pg/ml (p = 0.012). Histologic changes such as myofiber atrophy and cytoplasmic vacuolation, accompanied with interstitial fibrosis, were found predominantly in the left ventricle.
Conclusion: Repeated intracoronary infusions of doxorubicin represent a simple and reliable technique to produce dilated cardiomyopathy in the dog. This model can be used to evaluate the effects of new therapies, especially surgical treatments such as dynamic cardiomyoplasty and reduction ventriculoplasty, on dilated cardiomyopathy.

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