Toyoda Y, Okada M, Kashem M A
Department of Surgery, Kobe University School of Medicine, Japan.
J Thorac Cardiovasc Surg. 1998 Jun;115(6):1367-73. doi: 10.1016/S0022-5223(98)70221-1.
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.
Six closed-chest pure-bred 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.
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.
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.
尚未开发出一种简单且可重复的扩张型心肌病大型动物模型。本研究旨在建立犬扩张型心肌病模型。
对6只体重8至12千克（10±1.9千克）的闭胸纯种比格犬进行冠状动脉内注射阿霉素（阿霉素）。通过5F Judkins导管将低剂量（0.7毫克/千克）阿霉素注入左主冠状动脉。每周重复注射，共进行5周。我们评估了在五次冠状动脉内注射阿霉素前、注射后1个月和3个月对心脏血流动力学、心室大小、神经内分泌系统和心脏超微结构的影响。
治疗3个月后，缩短分数（平均值±平均标准误差）从36.5%±0.8%降至21.7%±1.4%（p = 0.0003），左心室射血分数从71.0%±3.3%降至36.3%±5.5%（p = 0.001）。左心室舒张末期内径从27.8±0.9增加到35.5±0.6毫米（p = 0.003），左心室舒张末期容积从27.5±1.8增加到38.3±1.9毫升（p = 0.015）。左心室舒张末期压力从8.5±0.9增加到14.5±1.1毫米汞柱（p = 0.01），每搏输出量从16.7±0.9减少到11.5±0.4毫升（p = 0.001）。在同一时期，血浆去甲肾上腺素浓度也从114±27.4增加到423±88.9皮克/毫升（p = 0.024），血浆心钠素水平从33.8±7.0增加到76.5±14.8皮克/毫升（p = 0.012）。组织学变化，如肌纤维萎缩和细胞质空泡化，并伴有间质纤维化，主要在左心室发现。
重复冠状动脉内注射阿霉素是一种在犬中产生扩张型心肌病的简单可靠技术。该模型可用于评估新疗法，特别是如动力性心肌成形术和减容心室成形术等外科治疗对扩张型心肌病的效果。
