Efferent vagal nerve stimulation protects heart against ischemia-induced arrhythmias by preserving connexin43 protein.
BACKGROUND
Myocardial ischemia (MI) leads to derangements in cellular electrical stability and the generation of lethal arrhythmias. Vagal nerve stimulation has been postulated to contribute to the antifibrillatory effect. Here, we suggest a novel mechanism for the antiarrhythmogenic properties of vagal stimulation during acute MI.


RESULTS
Under anesthesia, Wistar rats underwent 30 minutes of left coronary artery (LCA) ligation with vagal stimulation (MI-VS group, n=11) and with sham stimulation (MI-SS group, n=12). Eight of the 12 rats in the MI-SS group had ventricular tachyarrhythmia (VT) during 30-minute LCA ligation; on the other hand, VT occurred in only 1 of the 11 rats in the MI-VS group (67% versus 9%, respectively). Atropine administration abolished the antiarrhythmogenic effect of vagal stimulation. Immunoblotting revealed that the MI-SS group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the MI-VS group showed only a slight reduction compared with the sham operation and sham stimulation group (37+/-20% versus 79+/-18%). Immunohistochemistry confirmed that the MI-induced loss of Cx43 from intercellular junctions was prevented by vagal stimulation. In addition, studies with rat primary-cultured cardiomyocytes demonstrated that acetylcholine effectively prevented the hypoxia-induced loss of phosphorylated Cx43 and ameliorated the loss of cell-to-cell communication as determined by Lucifer Yellow dye transfer assay, which supports the in vivo results.


CONCLUSIONS
Vagal nerve stimulation exerts antiarrhythmogenic effects accompanied by prevention of the loss of phosphorylated Cx43 during acute MI and thus plays a critical role in improving ischemia-induced electrical instability.
Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi, Japan.
Motonori
M
Ando
Rajesh G
RG
Katare
Yoshihiko
Y
Kakinuma
Dongmei
D
Zhang
Fumiyasu
F
Yamasaki
Kazuyo
K
Muramoto
Takayuki
T
Sato
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002450:Cell Communication; D018031:Connexin 43 / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004525:Efferent Pathways; D004599:Electric Stimulation Therapy; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014630:Vagus Nerve
D018031:Connexin 43; D000109:Acetylcholine