Cardiac-directed expression of adenylyl cyclase VI facilitates atrioventricular nodal conduction.
J Am Coll Cardiol
; 48(3): 559-65, 2006 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-16875984
ABSTRACT
OBJECTIVES:
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.
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Banco de datos:
MEDLINE
Asunto principal:
Nodo Atrioventricular
/
Adenilil Ciclasas
/
Miocardio
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Año:
2006
Tipo del documento:
Article