This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.01.082v1 48/3/559    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Sastry, A. Articles by Narayan, S. M. Search for Related Content PubMed PubMed Citation Articles by Sastry, A. Articles by Narayan, S. M.

PRECLINICAL STUDY

Cardiac-Directed Expression of Adenylyl Cyclase VI Facilitates Atrioventricular Nodal Conduction

Ashwani Sastry, BS^_*, Elizabeth Arnold, BA^_*, Hunaid Gurji, BS^_*,, Atsushi Iwasa, MD^_*,, Hanh Bui, MD^_*,, Alborz Hassankhani, MD, PhD^_*,, Hemal H. Patel, PhD^_*, James R. Feramisco, PhD^_*, David M. Roth, MD^_*,, N. Chin Lai, PhD, H. Kirk Hammond, MD^_*, and Sanjiv M. Narayan, MB, MD^_*,,_*

^_* University of California, San Diego, California
Veterans Affairs San Diego Healthcare System, San Diego, California

Manuscript received August 1, 2005; revised manuscript received December 12, 2005, accepted January 5, 2006.

^_* Reprint requests and correspondence: Dr. Sanjiv M. Narayan, Director of Electrophysiology, VA Medical Center, Co-Director, Electrophysiology Training Program, University of California, San Diego, Cardiology 111A, 3350 La Jolla Village Drive, San Diego, California 92161. (Email: snarayan{at}ucsd.edu).

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.

Abbreviations and Acronyms   ACVI = adenylyl cyclase type VI   AH = atrial-to-His   ANOVA = analysis of variance   AV = atrioventricular   AVERP = atrioventricular nodal effective refractory period   ßAR = beta-adrenergic receptor   cAMP = cyclic adenosine monophosphate   CHF = congestive heart failure   CL = cycle length   CSNRT = corrected sinus node recovery time   ECG = electrocardiogram   EPS = electrophysiologic study   ERP = effective refractory period   MHC = major histocompatibility complex   SNRT = sinus node recovery time   VA = ventriculo-atrial

This article has been cited by other articles:

				V. J. Watts Adenylyl Cyclase Isoforms as Novel Therapeutic Targets: An Exciting Example of Excitotoxicity Neuroprotection Mol. Interv., April 1, 2007; 7(2): 70 - 73. [Abstract] [Full Text] [PDF]