HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in 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 Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Xing, D. Articles by Martins, J. B. Search for Related Content PubMed PubMed Citation Articles by Xing, D. Articles by Martins, J. B.

Pharmacological stimulation of cardiac gap junction coupling does not affect ischemia-induced focal ventricular tachycardia or triggered activity in dogs

¹Department of Internal Medicine, Carver College of Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, Iowa; and ²Zealand Pharma, Glostrup, Denmark

Submitted 19 July 2004 ; accepted in final form 4 October 2004

The role of gap junction intercellular communication (GJIC) in ischemia-induced focal ventricular tachycardia (VT) is unknown. We have developed a new, stable antiarrhythmic peptide analog named ZP123 that selectively increases GJIC and prevents reentrant VT. Our aim in this study was to use ZP123 as a tool to assess the role of GJIC on occurrence of ischemia-induced focal VT and triggered activity (TA) due to delayed afterdepolarizations (DADs). Focal VT was induced by programmed stimulation in -chloralose-anesthetized, open-chest dogs 1–4 h after coronary artery occlusion. Three-dimensional activation mapping was done using 6 bipolar electrograms on each of 23 multipolar needles in the risk zone. Dogs were randomly assigned to receive either saline or ZP123 cumulatively at three dose levels (an intravenous bolus followed by a 30-min infusion per dose). Attempts to induce VT were repeated in each dose. Mass spectrometry was used to measure plasma ZP123 concentrations. Standard microelectrode techniques were used for in vitro study of DADs and TA. Twenty-six dogs with focal VT were included. ZP123 did not affect the inducibility of focal VT at any plasma concentrations vs. saline (0.8 ± 0.1 nM, 77 vs. 75%; 7.8 ± 0.4 nM, 86 vs. 77%; and 78.8 ± 5.0 nM, 77 vs. 91%). In vitro, ZP123 did not affect the induction of DADs (12/12) and TAs (10/10) in ischemic tissues or tissue removed from the origin of focal VT (DADs, 8/8; TAs, 4/4). Therefore, although indirect, the data with the doses and concentrations used suggest that GJIC may not play a major role in the genesis of focal activity in the ischemic models studied.

gap junction intercellular communication; myocardial; delayed afterdepolarizations

This article has been cited by other articles:

				X. Lin, C. Zemlin, J. K. Hennan, J. S. Petersen, and R. D. Veenstra Enhancement of ventricular gap-junction coupling by rotigaptide Cardiovasc Res, August 1, 2008; 79(3): 416 - 426. [Abstract] [Full Text] [PDF]

				J.-q. Zhong, G. Laurent, P. P.-S. So, Xudong Hu, J. K. Hennan, and P. Dorian Effects of Rotigaptide, a Gap Junction Modifier, on Defibrillation Energy and Resuscitation From Cardiac Arrest in Rabbits Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2007; 12(1): 69 - 77. [Abstract] [PDF]

				A. Shiroshita-Takeshita, M. Sakabe, K. Haugan, J. K. Hennan, and S. Nattel Model-Dependent Effects of the Gap Junction Conduction-Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs Circulation, January 23, 2007; 115(3): 310 - 318. [Abstract] [Full Text] [PDF]

				J. M. Guerra, T. H. Everett IV, K. W. Lee, E. Wilson, and J. E. Olgin Effects of the Gap Junction Modifier Rotigaptide (ZP123) on Atrial Conduction and Vulnerability to Atrial Fibrillation Circulation, July 11, 2006; 114(2): 110 - 118. [Abstract] [Full Text] [PDF]

				H. V.M. van Rijen, J. M.T. de Bakker, and T. A.B. van Veen Hypoxia, electrical uncoupling, and conduction slowing: Role of conduction reserve Cardiovasc Res, April 1, 2005; 66(1): 9 - 11. [Full Text] [PDF]