title: Further evidence for the role of gap junctions in the delayed antiarrhythmic effect of cardiac pacing.
abstract: The objective of this study was to provide evidence that gap junctions are involved in the delayed antiarrhythmic effect of cardiac pacing. Twenty-four dogs were paced through the right ventricle (4 × 5 min, rate of 240 beats/min) 24 h prior to a 25 min occlusion of the left anterior descending coronary artery. Some of these paced dogs were infused with 50 (n = 7) or 100 μmol/L (n = 7) of the gap junction uncoupler carbenoxolone (CBX), prior to and during the occlusion. Ten sham-paced dogs, subjected only to occlusion, served as the controls. Cardiac pacing markedly reduced the number of ectopic beats and episodes of ventricular tachycardia (VT), as well the incidence of VT and ventricular fibrillation during occlusion. The changes in severity of ischaemia and tissue electrical resistance were also less marked compared with the unpaced controls. Pacing also preserved the permeability of gap junctions, the phosphorylation of connexin43, and the structural integrity of the intercalated discs. The closing of gap junctions with CBX prior to and during ischaemia markedly attenuated or even abolished these protective effects of pacing.
  
  
  CONCLUSIONS
  Our results support the previous findings that gap junctions play a role in the delayed antiarrhythmic effect of cardiac pacing.
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720 Szeged, Dóm tér 12, Hungary.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Miskolczi
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720 Szeged, Dóm tér 12, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Gönczi
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720 Szeged, Dóm tér 12, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Kovács
authors.affiliation: b Department of Medical Biology, University of Szeged, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Seprényi
authors.affiliation: a Department of Pharmacology and Pharmacotherapy, University of Szeged, 6720 Szeged, Dóm tér 12, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Végh
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002229:Carbenoxolone / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D008297:Male; D013997:Time Factors
chemical_list: D002229:Carbenoxolone
keywords: arrhythmias; arythmies; carbenoxolone; carbénoxolone; cardioprotection; gap junction; ischaemia–reperfusion; ischémie–reperfusion; jonction gap