title: Modulation of cardiac autonomic neurotransmission by epicardial superfusion. Effects of hexamethonium and tetrodotoxin.
abstract: The heart contains superficial cardiac nerves whose effects may be modulated by pericardial fluid bathing the epicardium. We tested this hypothesis in open-chest dogs anesthetized with secobarbital. Oxygenated normal Tyrode's solution (NT) or NT containing hexamethonium, a ganglionic blocker (500 microM), or tetrodotoxin, a blocker of axonal neurotransmission (5 microM, TTX), was instilled into the pericardial cavity to superfuse the epicardium of the whole heart. During each superfusion, effective refractory period (ERP) was determined in deep intramyocardium (greater than or equal to 4 mm in depth from the epicardium) of anterior and posterior left ventricle and in the subendocardium of the right ventricle in the baseline state and during bilateral cervical vagal stimulation (VS) or ansae subclaviae stimulation (SS). Lengthening of ERP induced by VS during superfusion with NT (6.9 +/- 0.3 msec, mean +/- SEM, n = 36) was eliminated during subsequent superfusion with hexamethonium (0.9 +/- 0.5 msec, p less than 0.001). Hexamethonium also prevented sinus arrest induced by VS but did not affect shortening of ERP induced by SS (17.3 +/- 1.3 to 16.6 +/- 1.0 msec, n = 26). TTX suppressed VS-induced changes in ERP (6.3 +/- 0.3 to 1.5 +/- 0.5 msec, n = 32, p less than 0.001) and SS-induced changes in ERP (18.8 +/- 1.6 to 6.0 +/- 0.9 msec, n = 23, p less than 0.001) but did not affect changes in ERP induced by intravenous administration of norepinephrine or methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: T
authors.initials: T
authors.lastname: Miyazaki
authors.forename: H P
authors.initials: HP
authors.lastname: Pride
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005730:Ganglionic Blockers; D006323:Heart Arrest / Q000209:etiology / Q000517:prevention & control; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles; D006439:Hemodynamics / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010496:Pericardium / Q000502:physiology*; D012032:Refractory Period, Electrophysiological; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D007552:Isotonic Solutions; D008688:Methacholine Compounds; C037692:Tyrode's solution; D016210:Methacholine Chloride; D018738:Hexamethonium; D013779:Tetrodotoxin; D009638:Norepinephrine