title: Blunted functional responses to pre- and postjunctional sympathetic stimulation in hibernating myocardium.
abstract: Regional reductions in norepinephrine-tracer uptake are found in pigs with hibernating myocardium. Clinical studies would suggest that this is evidence for denervation; however, the functional responses to sympathetic stimulation have not been evaluated, and our previous studies with beta-adrenergic stimulation have not suggested denervation hypersensitivity. Therefore, pigs were chronically instrumented to produce hibernating myocardium characterized by chronic regional dysfunction and histological viability. Open-chest studies were performed to determine changes in regional function in response to both pre- and postjunctional stimulation. Regional segment shortening was reduced at rest in hibernating myocardium compared with controls (13 +/- 3% vs. 27 +/- 3%, P = 0.004). During stellate ganglion stimulation, regional function increased in both groups of animals (P = 0.008 vs. baseline), but the increase in hibernating myocardium was blunted compared with controls (Delta%, 3 +/- 2% vs. 8 +/- 3%, P = 0.04). Similar results occurred with intracoronary tyramine (10 mug/kg). Functional improvement during intravenous epinephrine infusion (0.35 mug.kg(-1).min(-1)) was also blunted in hibernating myocardium compared with controls (Delta%, 7 +/- 1% vs. 15 +/- 2%, P = 0.04). Even when the improvement in function was expressed relative to the reduced baseline, there was no evidence for catecholamine-mediated hypersensitivity in hibernating myocardium. We therefore conclude that functional responses to both pre- and postjunctional sympathetic stimulation are blunted in pigs with hibernating myocardium. In contrast to previous studies of infarcted, denervated, and acutely stunned myocardium, there is no catecholamine-induced hypersensitivity in hibernating myocardium. These data suggest a downregulation in functional responses to stimulation that would protect hibernating myocardium from demand-induced ischemia at the expense of contractile reserve during sympathetic stimulation.
authors.affiliation: Center for Research in Cardiovascular Medicine, University at Buffalo, Buffalo, New York 14214, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Ovchinnikov
authors.forename: Gen
authors.initials: G
authors.lastname: Suzuki
authors.forename: John M
authors.initials: JM
authors.lastname: Canty
authors.forename: James A
authors.initials: JA
authors.lastname: Fallavollita
mesh_terms: D000818:Animals; D006321:Heart / Q000294:innervation* / Q000503:physiopathology*; D009200:Myocardial Contraction / Q000502:physiology; D017682:Myocardial Stunning / Q000503:physiopathology*; D013233:Stellate Ganglion / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology; D013610:Tachycardia / Q000503:physiopathology; D014439:Tyramine / Q000494:pharmacology
chemical_list: D013566:Sympathomimetics; D014439:Tyramine