title: Cardiac-directed expression of adenylyl cyclase VI facilitates atrioventricular nodal conduction.
abstract: OBJECTIVE
  The purpose of this study was to test the hypothesis that cardiac-directed expression of adenylyl cyclase VI (AC(VI)) facilitates atrioventricular (AV) nodal conduction.
  
  
  BACKGROUND
  Cardiac-directed expression of AC(VI), unlike other strategies to increase cyclic adenosine monophosphate generation, reduces mortality in murine cardiomyopathy. Recent reports suggest that AC(VI) expression may also protect against lethal bradycardia.
  
  
  METHODS
  We performed immunofluorescence staining for AC(VI) in the AV node of transgenic mice. We then performed electrophysiologic studies (EPSs) using a 1.7-F octapolar catheter at the AV junction in 11 transgenic AC(VI) mice and 14 control mice.
  
  
  RESULTS
  Immunofluorescence staining revealed increased AC(VI) expression in the AV node of transgenic mice versus controls. During EPS, AV intervals approximated PR intervals (R2 = 0.99) and related linearly to atrial-to-His intervals (R2 = 0.98; both p < 0.0001). Thus, we studied AV intervals to avoid electrocardiogram pacing artifacts and inconsistent inscription of His bundle electrograms. At baseline, AC(VI) mice had shorter AV intervals (47 +/- 9 ms) than controls (57 +/- 11 ms; p = 0.02), despite similar sinus rates. In pacing, AV intervals were shorter in AC(VI) mice than controls for a wide cycle-length range (p < 0.01). The AC(VI) mice also had shorter AV Wenckebach cycle lengths (AC(VI): 114 +/- 12 ms; control: 131 +/- 28 ms; p = 0.05) and ventriculo-atrial effective refractory periods (AC(VI): 97 +/- 21 ms; control: 127 +/- 15 ms; p = 0.05). We observed no differences between groups in sinus node function, and ventricular arrhythmias were not inducible.
  
  
  CONCLUSIONS
  Cardiac-directed expression of AC(VI) facilitates AV nodal conduction without altering sinus node function. These results suggest the need to define a role for AC(VI) gene transfer in treating diseases of AV conduction.
authors.affiliation: University of California, San Diego, California 92161, USA.
authors.forename: Ashwani
authors.initials: A
authors.lastname: Sastry
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Arnold
authors.forename: Hunaid
authors.initials: H
authors.lastname: Gurji
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iwasa
authors.forename: Hanh
authors.initials: H
authors.lastname: Bui
authors.forename: Alborz
authors.initials: A
authors.lastname: Hassankhani
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.forename: James R
authors.initials: JR
authors.lastname: Feramisco
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
authors.forename: N Chin
authors.initials: NC
authors.lastname: Lai
authors.forename: H Kirk
authors.initials: HK
authors.lastname: Hammond
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D001283:Atrioventricular Node / Q000201:enzymology / Q000502:physiology*; D002304:Cardiac Pacing, Artificial; D004198:Disease Susceptibility; D004594:Electrophysiology; D006329:Heart Conduction System / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000201:enzymology*
chemical_list: D000262:Adenylyl Cyclases; C121100:adenylyl cyclase 6