Modulation of cardiac autonomic neurotransmission by epicardial superfusion. Effects of hexamethonium and tetrodotoxin

T. Miyazaki, H. P. Pride, D. P. Zipes

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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 μM), or tetrodotoxin, a blocker of axonal neurotransmission (5 μM, 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 (≥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>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<0.001) and SS-induced changes in ERP (18.8±1.6 to 6.0±0.9 msec, n=23, p<0.001) but did not affect changes in ERP induced by intravenous administration of norepinephrine or methacholine. This indicates that the suppressive effect of TTX on neurally induced changes in ERP was due to an inhibition of neutrotransmission and not on the response of the effector site to the neurotransmitter. We conclude that 1) vagal ganglia that innervate both ventricles as well sinus node are distributed superficially and are blocked by epicardial superfusion with hexamethonium, 2) the epicardium lacks sympathetic ganglia, and 3) both vagal and sympathetic axons at some point travel superficially during their course in the heart and are blocked by TTX. These results suggest that substances in the pericardial fluid, whether normally secreted or present due to disease, have the potential to modulate autonomic neural transmission to the heart.

Original languageEnglish (US)
Pages (from-to)1212-1219
Number of pages8
JournalCirculation research
Issue number5
StatePublished - 1989

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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