Atrial Electrical remodeling by rapid pacing in the isolated rabbit heart : Effects of Ca++ and K+ channel blockade

• Published in: Journal of interventional cardiac electrophysiology 1998-03, Vol.2 (1), p.15-23
• Main Authors: WOOD, M. A, CAPONI, D, SYKES, A. M, WENGER, E. J
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - pharmacology; Action Potentials - drug effects; Analysis of Variance; Animals; Atrial Fibrillation - drug therapy; Atrial Fibrillation - physiopathology; Atrial Fibrillation - therapy; Atrial Function - drug effects; Atrial Function - physiology; Atrial Function, Left - drug effects; Atrial Function, Left - physiology; Atrial Function, Right - drug effects; Atrial Function, Right - physiology; Atrioventricular Node - drug effects; Atrioventricular Node - physiopathology; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiac Pacing, Artificial; Cardiology. Vascular system; Electrocardiography - drug effects; Female; Heart; Male; Medical sciences; Neural Conduction - drug effects; Neural Conduction - physiology; Nickel - pharmacology; Potassium Channel Blockers; Rabbits; Refractory Period, Electrophysiological - drug effects; Refractory Period, Electrophysiological - physiology; Time Factors; Verapamil - pharmacology
• ISSN: 1383-875X; 1572-8595
• DOI: 10.1023/A:1009752405126

Electrical remodeling describes atrial electrophysiologic changes that occur following atrial fibrillation. The mechanism(s) responsible for this phenomenon is not well understood. The purpose of this study was to examine the effects of rapid atrial pacing on atrial action potential duration, conduction time and refractoriness in the isolated rabbit heart. The effects of Ca++ and K+ blockade in this model were also studied. Monophasic action potential recordings were made from 12 epicardial atrial sites in 50 isolated perfused rabbit heart preparations. These recordings were analyzed for activation time (AT), 90% action potential duration (APD) and conduction times (CT) measured at a 250 msec cycle length. Atrial effective refractory periods (ERP) were determined at a 200 msec cycle length. All measurements were made at baseline and repeated after 2 hours of biatrial pacing at 250 msec (control group, n = 10) or 2 hours of rapid biatrial pacing (approximately 80 msec) in 4 groups: rapid pacing alone (rapid pacing group); rapid pacing in the presence of 0.1 mM verapamil (verapamil group) for L-type Ca++ channel blockade; rapid pacing with 1 mM 4-aminopyridine (4-AP group) for K+ channel blockade; and rapid pacing with 50 microM nickel chloride (Ni++ group) for T-type Ca++ channel blockade (n = 10 each group). All baseline and post pacing measurements were taken in the presence of Ca++ or K+ blockers for the respective groups. After rapid atrial pacing alone the average APD shortened by 8.2 +/- 10.4 msec compared to 3.6 +/- 12.5 msec shortening for control group (p = 0.002). The shortening of APD was uniform at all recording sites. For the rapid pacing group, CT was unchanged for right to left atrial conduction but shortened significantly for left to right atrial conduction (26.8 +/- 1.9 msec at baseline to 22.3 +/- 4.1 msec post pacing, p = 0.005). Conduction times were unchanged in the control group. The dispersion of repolarization was unchanged by rapid pacing alone. The decrease in APD from baseline to post rapid pacing was similar to the control group for those hearts treated with verapamil and 4-AP (1.5 +/- 12.3 and 4.7 +/- 10.4 msec, respectively, both p > or = 0.18 vs control group). The decrease in APD was significantly greater for the Ni++ group (11.8 +/- 14.3 msec) than for either the control group or rapid pacing group (both p < or = 0.023). The dispersion of repolarization was increased only in the 4-AP group post rapid pacing (41.7 +/- 6.2 mse