Regional Desensitization of β-Adrenergic Receptor Signaling in Swine With Chronic Hibernating Myocardium

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Abstract
Contractile reserve during submaximal β-adrenergic stimulation is attenuated in patients and swine with hibernating myocardium. We tested the hypothesis that this arises as a regional adaptive response in β-adrenergic adenylyl cyclase coupling. Pigs (n=8) were studied 3 months after instrumentation with a left anterior descending artery (LAD) stenosis when flow (LAD, 0.7±0.2 versus 1.2±0.1 mL/min per gram in normal remote; PPP=NS), responses to isoproterenol were blunted (LAD, 83±6 versus 146±25 pmol/mg per minute in remote; PP2/Gsα ratio increased (LAD, 1.8±0.3 versus 0.99±0.3 in remote myocardium; P<0.05), although GppNHp-stimulated cAMP production was equivocally reduced. Forskolin responses were unchanged and similar to shams. These data indicate regional attenuation of β-receptor adenylyl cyclase signaling in hibernating myocardium. This blunts the local contractile response to β-adrenergic stimulation and may serve to protect against a myocardial supply/demand imbalance when external determinants of myocardial workload increase during sympathetic activation.