Chronic cardiac failure induced by coronary artery ligation in lewis inbred rats. Liu, Yun-He, Xiao-Ping Yang, Omar Nass, Hani N. Sabbah, Edward Peterson, and Oscar A. Carretero. Hypertension and Vascular Research Division, Division of Cardiovascular Medicine and Department of Biostatistics and Research Epidemiology, Heart and Vascular Institute, Henry Ford Hospital, Detroit, MI 48202
APStracts 3:0400H, 1996.
Rat models of heart failure (HF) secondary to myocardial infarction (MI) are useful in studying progression of cardiac dysfunction and testing therapeutic approaches. Sprague-Dawley rats (SD) are frequently used; however, this model is hampered by high mortality and marked variability in infarct size and cardiac dysfunction, necessitating large numbers of rats and prolonged follow-up when studying progression of dysfunction. In the present work, we developed a model of HF utilizing Lewis inbred rats. Ligation of the left anterior descending coronary artery in Lewis rats produced more uniform and larger infarcts (40 +/- 1.7% vs 28 +/- 2.3%; p < 0.001) and lower mortality (16% vs 36%; p < 0.001) than in SD rats. Using this rat model, we further studied the course of left ventricular (LV) dysfunction and enlargement from 1 week to 6 months after MI using cineventriculography. LV end-systolic volume (ESV) and end-diastolic volume (EDV) were determined using the area-length method. LV ejection fraction (LVEF) ranged between 0.57 and 0.62 in controls; following MI, it decreased significantly to 0.48 +/- 0.04 at 1 week, 0.36 +/- 0.02 at 2 weeks, 0.48 +/- 0.02 at 1 month, 0.35 +/- 0.03 at 2 months, 0.30 +/- 0.02 at 3 months, 0.31 +/- 0.02 at 4 months, and 0.24 +/- 0.02 at 6 months (p < 0.001, MI vs sham). LVEDV in controls ranged between 0.32 and 0.42 ml; it increased to 0.48 +/- 0.04 at 1 week, 0.46 +/- 0.02 at 2 weeks, and 0.46 +/- 0.03 ml at 1 month. It markedly increased to 0.79 +/- 0.03, 0.79 +/- 0.06, 0.78 +/- 0.03 and 0.80 +/- 0.05 ml at 2, 3, 4 and 6 months after infarction, respectively (p < 0.001 vs sham). LV end-diastolic pressure was significantly elevated at all time points. Thus coronary ligation in Lewis inbred rats produces uniformly large infarcts with low mortality, progressive LV dysfunction and increased LV chamber size. This model may be useful in studying chronic HF secondary to myocardial infarction.

Received 15 December 1995; accepted in final form 26 August 1996.
APS Manuscript Number H1181-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996