Variability of contractile reserve in hibernating myocardium: Dependence on the method of inotropic stimulation

Objective: Contractile reserve during graded β-adrenergic stimulation identifies viability in patients with left ventricular dysfunction. Nevertheless, contractile reserve is frequently absent in viable, chronically dysfunctional myocardium with reduced resting flow (hibernating myocardium). The goal of this study was to evaluate the mechanisms responsible for limited contractile reserve in hibernating myocardium. Methods: Pigs were chronically instrumented with a left anterior descending coronary artery (LAD) stenosis to produce hibernating myocardium; and regional flow, function and hemodynamics were assessed during graded β-adrenergic stimulation (epinephrine). Results: The chronic LAD stenosis produced a critical reduction in coronary flow reserve with regional reductions in resting subendocardial flow (0.69±0.05 vs. 1.03±0.11 ml/min/g in shams, P<0.05) and wall thickening (2.0±0.4 vs. 4.3±0.4 mm in shams, P<0.05), consistent with hibernating myocardium. In sham controls, LAD flow and function increased during graded, steady-state increases in epinephrine. Nevertheless, despite similar external determinants of demand in animals with hibernating myocardium, neither subendocardial flow (peak response: 0.66±0.14 and peak dose: 0.58±0.13 ml/min/g, respectively) nor wall thickening (3.0±0.5 and 2.5±0.6 mm, respectively) increased during graded epinephrine infusion. However, during a transient epinephrine infusion to the maximum dose used in the graded protocol, flow remained unchanged (0.80±0.06 to 0.85±0.08 ml/min/g) but wall thickening improved (2.3±0.4 to 4.1±0.6 mm, P<0.05). Conclusions: These data indicate that variability in contractile reserve in hibernating myocardium is at least partly related to the protocol used for β-adrenergic stimulation. The blunted steady-state responses to β-adrenergic stimulation raise the possibility that, like moderate supply-induced ischemia, an exquisite matching between flow and function develops during moderate demand-induced ischemia. This prevents metabolic deterioration in hibernating myocardium but limits contractile function during increases in the external determinants of myocardial metabolism.