Stability of hibernating myocardium in pigs with a chronic left anterior descending coronary artery stenosis: Absence of progressive fibrosis in the setting of stable reductions in flow, function and coronary flow reserve

OBJECTIVES This study was performed to determine whether hibernating myocar dium is adaptive or is destined to undergo progressive irreversible injury. BACKGROUND Previous studies have suggested that hibernating myocardium even tually results in progressive dysfunction. Since serial studies cannot be p erformed in humans, the temporal progression of physiologic and structural adaptations was evaluated in pigs with hibernating myocardium. METHODS Pigs were instrumented with a left anterior descending coronary art ery (LAD) stenosis (1.5 mm) and underwent physiologic studies three to five months later to quantify regional function, perfusion and F-18-2-deoxygluc ose (FDG) uptake. Viability was confirmed by histology and contractile rese rve. Hibernating myocardium was characterized by severe regional dysfunctio n (centerline score, -1.9 +/- 0.1), reduced resting subendocardial flow (LA D: 0.85 +/- 0.03 vs. normal: 1.02 +/- 0.03 ml/min/g, p < 0.01), critically reduced subendocardial flow reserve (adenosine flow: 1.04 +/- 0.09 ml/min/g , p = NS vs. rest; epinephrine flow: 0.88 +/- 0.07 ml/min/g, p = NS vs. res t) and increased FDG uptake (0.022 +/- 0.002 vs. 0.014 +/- 0.001 ml/g/min, p < 0.01). Physiologic parameters were not different among animals studied at three (93 +/- 1 days, n = 27), four (118 +/- 2 days, n = 26) or five mon ths (150 +/- 6 days, n = 9). Pathology revealed a small increase in LAD con nective tissue (6.4 +/- 0.4% vs. 4.0 +/- 0.2%, p < 0.001), with no change o ver this time frame. CONCLUSIONS Thus, physiologic and structural features of hibernating myocar dium remain constant for at least two months. The absence of functional det erioration or progressive fibrosis suggests that hibernation is adaptive ra ther than an unstable physiology destined to progress to irreversible injur y. The stability of this model appears ideally suited for interventions tar geted to improve flow and function in chronically dysfunctional myocardium. (J Am Coll Cardiol 2001;37: 1989-95) (C) 2001 by the American College of C ardiology.