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 myocardium is adaptive or is destined to undergo progressive irreversible injury. BACKGROUND Previous studies have suggested that hibernating myocardium eventually results in progressive dysfunction. Since serial studies cannot be performed 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 artery (LAD) stenosis (1.5 mm) and underwent physiologic studies three to five months later to quantify regional function, perfusion and 18F-2-deoxyglucose (FDG) uptake. Viability was confirmed by histology and contractile reserve. RESULTS Hibernating myocardium was characterized by severe regional dysfunction (centerline score, −1.9 ± 0.1), reduced resting subendocardial flow (LAD: 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. rest) 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 months (150 ± 6 days, N = 9). Pathology revealed a small increase in LAD connective tissue (6.4 ± 0.4% vs. 4.0 ± 0.2%, p < 0.001), with no change over this time frame. CONCLUSIONS Thus, physiologic and structural features of hibernating myocardium remain constant for at least two months. The absence of functional deterioration or progressive fibrosis suggests that hibernation is adaptive rather than an unstable physiology destined to progress to irreversible injury. The stability of this model appears ideally suited for interventions targeted to improve flow and function in chronically dysfunctional myocardium.