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) Supplemental Table and Video All Versions of this Article: 293/2/H1223    most recent 00079.2007v1 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 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 (5) Citing Articles via Google Scholar Google Scholar Articles by Akar, F. G. Articles by Tomaselli, G. F. Search for Related Content PubMed PubMed Citation Articles by Akar, F. G. Articles by Tomaselli, G. F.

Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure

Division of Cardiology and Institute for Computational Medicine, Johns Hopkins University, Baltimore, Maryland

Submitted 18 January 2007 ; accepted in final form 12 April 2007

End-stage heart failure (HF) is characterized by changes in conduction velocity (CV) that predispose to arrhythmias. Here, we investigate the time course of conduction changes with respect to alterations in connexin 43 (Cx43) properties and mechanical function during the development of HF. We perform high-resolution optical mapping in arterially perfused myocardial preparations from dogs subjected to 0, 3, 7, 14, and 21 days of rapid pacing to produce variable degrees of remodeling. CV is compared with an index of mechanical function [left ventricular end-diastolic pressure (LVEDP)] and with dynamic changes in the expression, distribution, and phosphorylation of Cx43. In contrast to repolarization, CV was preserved during early stages of remodeling (3 and 7 days) and significantly reduced at later stages, which were associated with marked increases in LVEDP. Measurements of differentially phosphorylated Cx43 isoforms revealed early, sustained downregulation of pan-Cx43 that preceded changes in CV and LVEDP, a gradual rise in a dephosphorylated Cx43 isoform to over twofold baseline levels in end-stage HF, and a late abrupt increase in pan-Cx43, but not dephosphorylated Cx43, lateralization. These data demonstrate that 1) CV slowing occurs only at advanced stages of remodeling, 2) total reduction of pan-Cx43 is an early event that precedes mechanical dysfunction and CV slowing, 3) changes in Cx43 phosphorylation are more closely associated with the onset of HF, and 4) Cx43 lateralization is a late event that coincides with marked CV reduction. These data reveal a novel paradigm of remodeling based on the timing of conduction abnormalities relative to changes in Cx43 isoforms and mechanical dysfunction.

electrical remodeling; connexin; arrhythmias

This article has been cited by other articles:

				Z. Gao, A. S. Barth, D. DiSilvestre, F. G. Akar, Y. Tian, A. Tanskanen, D. A. Kass, R. L. Winslow, and G. F. Tomaselli Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling Physiol Genomics, November 12, 2008; 35(3): 222 - 230. [Abstract] [Full Text] [PDF]

				G. Plank, A. Prassl, E. Hofer, and N. A. Trayanova Evaluating Intramural Virtual Electrodes in the Myocardial Wedge Preparation: Simulations of Experimental Conditions Biophys. J., March 1, 2008; 94(5): 1904 - 1915. [Abstract] [Full Text] [PDF]

				B. Burstein and S. Nattel Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 802 - 809. [Abstract] [Full Text] [PDF]

				V. Lionetti, L. Guiducci, A. Simioniuc, G. D. Aquaro, C. Simi, D. De Marchi, S. Burchielli, L. Pratali, M. Piacenti, M. Lombardi, et al. Mismatch between uniform increase in cardiac glucose uptake and regional contractile dysfunction in pacing-induced heart failure Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2747 - H2756. [Abstract] [Full Text] [PDF]