CHRONIC HEART-FAILURE INDUCED BY CORONARY-ARTERY LIGATION IN LEWIS INBRED RATS

Rat models of heart failure (HF) secondary to myocardial infarction (M I) are useful in studying the progression of cardiac dysfunction and i n testing therapeutic approaches. Sprague-Dawley rats are frequently u sed; however, this model is hampered by high mortality and a marked va riability in infarct size and cardiac dysfunction, necessitating large numbers of rats and prolonged follow-up when studying the progression of dysfunction. In the present work, we developed a model of HF utili zing Lewis inbred rats. Ligation of the left anterior descending coron ary 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 Sprague-Dawley rats. Using this rat model, we furth er studied the course of left ventricular (LV) dysfunction and enlarge ment from 1 wk to 6 mo after MI with cineventriculography. LV end-syst olic volume and end-diastolic volume were determined with the area-len gth method. LV ejection fraction ranged between 0.57 and 0.62 in contr ol rats; after MI, it decreased significantly to 0.48 +/- 0.04 at 1 wk , 0.36 +/- 0.02 at 2 wk, 0.48 +/- 0.02 at 1 mo, 0.35 +/- 0.03 at 2 mo, 0.30 +/- 0.02 at 3 mo, 0.31 +/- 0.02 at 4 mo, and 0.24 +/- 0.02 at 6 mo (P < 0.001, MI vs. sham). LV end-diastolic volume in control rats r anged between 0.32 and 0.42 ml; it increased to 0.48 +/- 0.04 ml at 1 wk, 0.46 +/- 0.02 ml at 2 wk, and 0.46 +/- 0.03 ml at 1 mo. It markedl y 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 mo, respectively, after MI (P < 0.001 vs. sham). LV end-diastolic pressure was significantly elevated at all ti me points. Thus coronary ligation in Lewis inbred rats produces unifor mly large infarcts with low mortality, progressive LV dysfunction, and increased LV chamber size. This model may be useful in studying chron ic HF secondary to MI.