© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
Acute ischemia-induced gap junctional uncoupling and arrhythmogenesis
Experimental and Molecular Cardiology Group, Department of Clinical and Experimental Cardiology, Academic Medical Center, PO Box 22700, Amsterdam 1100 DE, The Netherlands
* Corresponding author. Tel.: +31-20-5663266; fax: +31-20-6975458. Email address: j.r.degroot{at}amc.uva.nl r.coronel{at}amc.uva.nl
Sudden cardiac death forms a major cause of mortality. Myocardial ischemia-induced ventricular fibrillation (VF) is frequently the underlying mechanism. Ventricular arrhythmias arise in two distinct phases during the first hour of ischemia. The first, the 1A phase, has been extensively studied, and few studies relate to the 1B phase. The latter is associated with intercellular electrical uncoupling, mediated by decreased conductance of gap junction channels.
Although the relation between gap junctional uncoupling and decreased conduction velocity appears clear under normoxic conditions, additional factors contribute to conduction slowing during ischemia, and VF occurs preferentially at moderate levels of uncoupling. A potential mechanism of arrhythmias depends on temporary electrotonic depression of intrinsically viable tissue by the large bulk of the ischemic zone. This causes conduction slowing and conduction block in the surviving layers, leading to arrhythmias. These arrhythmias then resolve with progression of uncoupling. It is unknown whether either accelerated uncoupling or maintenance of gap junctional communication is antiarrhythmic. Ischemic preconditioning postpones both gap junctional uncoupling and occurrence of VF. Given the burden of sudden death and the large number of casualties in the low-risk population, there is, even in the era of implantable cardiac defibrillators, need for further understanding the mechanism of ischemia-induced VF.
KEYWORDS Ischemia; Gap junctions; Ventricular arrhythmia; Cellular uncoupling; Connexin; Arrhythmia mechanism
Time for primary review 28 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. K. Hennan, R. E. Swillo, G. A. Morgan, E. I. Rossman, J. Kantrowitz, J. Butera, J. S. Petersen, S. J. Gardell, and G. P. Vlasuk GAP-134 ([2S,4R]-1-[2-Aminoacetyl]4-Benzamidopyrrolidine-2-Carboxylic Acid) Prevents Spontaneous Ventricular Arrhythmias and Reduces Infarct Size During Myocardial Ischemia/Reperfusion Injury in Open-Chest Dogs Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2009; 14(3): 207 - 214. [Abstract] [PDF]
|
|
|
|
 |
|
 Y. Shimoni, T. Emmett, R. Schmidt, A. Nygren, and G. Kargacin Sex-dependent impairment of cardiac action potential conduction in type 1 diabetic rats Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1442 - H1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Naitoh, T. Yano, T. Miura, T. Itoh, T. Miki, M. Tanno, T. Sato, H. Hotta, Y. Terashima, and K. Shimamoto Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H396 - H403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. del Rio, T. A. Dawson, B. D. Clymer, D. J. Paterson, and G. E. Billman Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation Exp Physiol, August 1, 2008; 93(8): 931 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. del Rio, P. I. McConnell, M. Kukielka, R. Dzwonczyk, B. D. Clymer, M. B. Howie, and G. E. Billman Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death J Appl Physiol, February 1, 2008; 104(2): 386 - 393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Papp, M. Gonczi, M. Kovacs, G. Seprenyi, and A. Vegh Gap junctional uncoupling plays a trigger role in the antiarrhythmic effect of ischaemic preconditioning Cardiovasc Res, June 1, 2007; 74(3): 396 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. McKinnon, D. Lidington, M. Bolon, Y. Ouellette, G. M. Kidder, and K. Tyml Reduced arteriolar conducted vasoconstriction in septic mouse cremaster muscle is mediated by nNOS-derived NO Cardiovasc Res, January 1, 2006; 69(1): 236 - 244. [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]
|
|
|
|
|
|
N. Zeevi-Levin, Y. D. Barac, Y. Reisner, I. Reiter, G. Yaniv, G. Meiry, Z. Abassi, S. Kostin, J. Schaper, M. R. Rosen, et al. Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes Cardiovasc Res, April 1, 2005; 66(1): 64 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Rosen, P. R. Brink, I. S. Cohen, and R. B. Robinson Genes, stem cells and biological pacemakers Cardiovasc Res, October 1, 2004; 64(1): 12 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dhein and H. J Jongsma Forming the network--gap junctions in the cardiovascular system Cardiovasc Res, May 1, 2004; 62(2): 225 - 227. [Full Text] [PDF]
|
|