LEFT-VENTRICULAR REMODELING IN MYOCARDIAL HIBERNATION

Background Left ventricular (LV) remodeling as a consequence of extens ive myocardial infarction has been well established in animal and huma n studies. This study was designed to determine whether regional LV dy sfunction with myocardial hibernation without transmural or extensive infarction could initiate the remodeling process. Methods and Results A severe left anterior descending coronary artery stenosis was created to reduce resting flow by approximate to 40% (from 0.99 +/- 0.10 to 0 .56 +/- 0.11 mL.min(-1).(g-1)) and was maintained for 7 days in 13 pig s. The reduction of regional coronary flow initially produced acute my ocardial ischemia, as evidenced by reduced regional wall thickening, f rom 37 +/- 3% at baseline to 9 +/- 7%, regional lactate production and a decrease in regional coronary venous pH. AU pigs had significant re gional LV dysfunction and reduced LV ejection fraction (41 +/- 11%). T he LV end-diastolic volume increased from 59 +/- 9 mt at baseline to 7 4 +/- 13 mt immediately after placement of the stenosis and to 78 +/- 17 mt 7 days later with hibernating myocardium. The LV mass did not ch ange immediately (60 +/- 8 g baseline versus 59 +/- 11 g immediately a fter creation of the stenosis) but increased modestly yet significantl y to 67 +/- 15 g after 7 days of myocardial hibernation subtending the severe LAD stenosis. The reductions of coronary flow and wall thicken ing were unchanged at 7 days, whereas myocardial lactate production re covered. By 4 weeks after restoration of LAD flow, regional function h ad recovered in all 7 pigs with follow-up. Of the 13 pigs, 6 were free from any evidence of myocardial infarction, and 4 had patchy necrosis involving less than 6% of the area at risk. Conclusions LV remodeling , which is commonly associated with extensive myocardial infarction, c an be initiated by regional dysfunctional hibernating myocardium resul ting from a severe coronary stenosis. Myocardial necrosis is not a pre requisite for LV remodeling in response to regional dysfunction.