Identification and characterization of atrioventricular parasympathetic innervation in humans.
BACKGROUND
We hypothesized that in humans there is an epicardial fat pad from which parasympathetic ganglia supply the AV node. We also hypothesized that the parasympathetic nerves innervating the AV node also innervate the right atrium, and the greatest density of innervation is near the AV nodal fat pad.


RESULTS
An epicardial fat pad near the junction of the left atrium and right inferior pulmonary vein was identified during cardiac surgery in seven patients. A ring electrode was used to stimulate this fat pad intraoperatively during sinus rhythm to produce transient complete heart block. Subsequently, temporary epicardial wire electrodes were sutured in pairs on this epicardial fat pad, the high right atrium, and the right ventricle by direct visualization during coronary artery bypass surgery in seven patients. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness at each catheter site was determined in the presence and absence of parasympathetic nerve stimulation (via the epicardial wires). In all seven patients, an AV nodal fat pad was identified. Fat pad stimulation during and after surgery caused complete heart block but no change in sinus rate. Fat pad stimulation decreased the right atrial effective refractory period at 1 cm (280 +/- 42 msec to 242 +/- 39 msec) and 2 cm (235 +/- 21 msec to 201 +/- 11 msec) from the fat pad (P = 0.04, compared with baseline). No significant change in atrial refractoriness occurred at distances >2 cm. The response to stimulation decreased as the distance from the fat pad increased.


CONCLUSIONS
For the first time in humans, an epicardial fat pad was identified from which parasympathetic nerve fibers selectively innervate the AV node but not the sinoatrial node. Nerves in this fat pad also innervate the surrounding right atrium.
Quan
Kara J
KJ
Division of Cardiology, University Hospitals of Cleveland, Case Western Reserve University, Ohio, USA. kquan@metrohealth.org
Lee
Jai H
JH
Van Hare
George F
GF
Biblo
Lee A
LA
Mackall
Judith A
JA
Carlson
Mark D
MD
D000273:Adipose Tissue / Q000187:drug effects / Q000294:innervation; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001283:Atrioventricular Node / Q000187:drug effects / Q000294:innervation* / Q000473:pathology*; D001285:Atropine / Q000008:administration & dosage; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000601:surgery; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D006325:Heart Atria / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009820:Ohio; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000473:pathology*; D010496:Pericardium / Q000187:drug effects / Q000294:innervation; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D001285:Atropine