(Circulation. 1999;99:704-712.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Mechanism of Acceleration of Functional Reentry in the Ventricle
Effects of ATP-Sensitive Potassium Channel Opener
From the Division of Cardiology, Burns and Allen Research Institute, Cedars-Sinai Medical Center, and the Department of Medicine, Division of Cardiology, UCLA School of Medicine, Los Angeles, Calif.
Correspondence to Hrayr S. Karagueuzian, PhD, Cedars-Sinai Medical Center, Davis Research Bldg, Room 6066, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail karagueuzian{at}csmc.edu
Background—The effect of effective refractory period (ERP) shortening on the vulnerability and characteristics of induced functional reentry in the ventricle remain poorly defined. We hypothesized that ERP shortening increases ventricular vulnerability to reentry and accelerates its rate, as is the case in the atrium.
Methods and Results—The epicardial surfaces of 19 isolated and superfused canine right ventricular slices (4x4 cm and <2 mm thick) were mapped with 480 bipolar electrodes 1.6 mm apart. Vulnerability was tested during pacing at a cycle length (CL) of 600 ms and with a single premature stimulus of 5-ms duration at increasing current strength of 1 to 100 mA. Cromakalim (10 µmol/L), an ATP-sensitive potassium channel opener, caused a significant (P<0.001) shortening of the ERP but had no effect on conduction velocity. Cromakalim increased (P<0.01) the vulnerability (product of current and the stimulus coupling interval) for reentry induction. Reentry had a significantly shorter CL and lasted for a longer duration (P<0.001). The central core around which the wave front rotated became smaller, which caused shortening of the CL of reentry. A significant (P<0.001) linear correlation was found between core size and reentry CL. These effects of cromakalim were reversible. Two-dimensional simulation studies using the modified Luo-Rudy I model of cardiac action potential, in which the refractory period was variably shortened by a progressive increase of the time-independent potassium conductance, reproduced the experimental findings.
Conclusions—ERP shortening by an ATP-sensitive potassium channel opener increases ventricular vulnerability to reentry and accelerates its rate by decreasing the core size around which the wave front rotates.
Key Words: reentry • tachycardia • potassium • cromakalim • waves
This article has been cited by other articles:
 |
|
 |
|
  O. E. Osadchii, B. H. Bentzen, and S. P. Olesen Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart Exp Physiol, April 1, 2009; 94(4): 434 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-R. Neuberger, U. Schotten, Y. Blaauw, D. Vollmann, S. Eijsbouts, A. van Hunnik, and M. Allessie Chronic Atrial Dilation, Electrical Remodeling, and Atrial Fibrillation in the Goat J. Am. Coll. Cardiol., February 7, 2006; 47(3): 644 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bursac and L. Tung Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: Formation of multi-wave functional reentries Cardiovasc Res, February 1, 2006; 69(2): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Comtois, J. Kneller, and S. Nattel Of circles and spirals: Bridging the gap between the leading circle and spiral wave concepts of cardiac reentry Europace, January 1, 2005; 7(s2): S10 - S20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Extramiana and C. Antzelevitch Amplified Transmural Dispersion of Repolarization as the Basis for Arrhythmogenesis in a Canine Ventricular-Wedge Model of Short-QT Syndrome Circulation, December 14, 2004; 110(24): 3661 - 3666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Coromilas, C. Costeas, B. Deruyter, S. M. Dillon, N. S. Peters, and A. L. Wit Effects of Pinacidil on Electrophysiological Properties of Epicardial Border Zone of Healing Canine Infarcts: Possible Effects of KATP Channel Activation Circulation, May 14, 2002; 105(19): 2309 - 2317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S Karagueuzian and P.-S. Chen Cellular mechanism of reentry induced by a strong electrical stimulus: Implications for fibrillation and defibrillation Cardiovasc Res, May 1, 2001; 50(2): 251 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ohara, K. Ohara, J.-M. Cao, M.-H. Lee, M. C. Fishbein, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Increased Wave Break During Ventricular Fibrillation in the Epicardial Border Zone of Hearts With Healed Myocardial Infarction Circulation, March 13, 2001; 103(10): 1465 - 1472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Koller, M. L. Riccio, and R. F. Gilmour Jr Effects of [K+]o on electrical restitution and activation dynamics during ventricular fibrillation Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2665 - H2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Patwardhan, S. Moghe, K. Wang, and F. Leonelli Frequency modulation within electrocardiograms during ventricular fibrillation Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H825 - H835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yashima, T. Ohara, J.-M. Cao, Y.-H. Kim, M. C. Fishbein, W. J. Mandel, P.-S. Chen, and H. S. Karagueuzian Nicotine increases ventricular vulnerability to fibrillation in hearts with healed myocardial infarction Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H2124 - H2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Chorro, J. Canoves, J. Guerrero, L. Mainar, J. Sanchis, L. Such, and V. Lopez-Merino Alteration of Ventricular Fibrillation by Flecainide, Verapamil, and Sotalol : An Experimental Study Circulation, April 4, 2000; 101(13): 1606 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. H. Samie, R. Mandapati, R. A. Gray, Y. Watanabe, C. Zuur, J. Beaumont, and J. Jalife A Mechanism of Transition From Ventricular Fibrillation to Tachycardia : Effect of Calcium Channel Blockade on the Dynamics of Rotating Waves Circ. Res., March 31, 2000; 86(6): 684 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Kim, M. Yashima, T.-J. Wu, R. Doshi, P.-S. Chen, and H. S. Karagueuzian Mechanism of Procainamide-Induced Prevention of Spontaneous Wave Break During Ventricular Fibrillation : Insight Into the Maintenance of Fibrillation Wave Fronts Circulation, August 10, 1999; 100(6): 666 - 674. [Abstract] [Full Text] [PDF]
|
|