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

Introduction: Electrical remodeling describes atrial electrophysiologic cha nges 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 du ration, conduction time and refractoriness in the isolated rabbit heart. Th e effects of Ca++ and K+ blockade in this model were also studied. Methods and Results: Monophasic action potential recordings were made from 12 epicardial atrial sites in 50 isolated perfused rabbit heart preparation s. These recordings were analyzed for activation time (AT), 90% action pote ntial 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 aft er 2 hours of biatrial pacing at 250 msec (control group, n = 10) or 2 hour s of rapid biatrial pacing (similar or equal to 80 msec) in 4 groups: rapid pacing alone (rapid pacing group); rapid pacing in the presence of 0.1mM v erapamil (verapamil group) for L-type Ca++ channel blockade; rapid pacing w ith 1 mM 4-aminopyridine (4-AP group) for K+ channel blockade; and rapid pa cing with 50 mu M nickel chloride (Ni++ group) for T-type Ca++ channel bloc kade (n = 10 each group). All baseline and post pacing measurements were ta ken 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 m sec 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 pa cing group, CT was unchanged for right to left atrial conduction but shorte ned 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 we re unchanged in the control group. The dispersion of repolarization was unc hanged by rapid pacing alone. The decrease in APD from baseline to post rap id pacing was similar to the control group for those hearts treated with ve rapamil and 4-AP (1.5 +/- 12.3 and 4.7 +/- 10.4 msec, respectively, both p greater than or equal to 0.18 vs control group). The decrease in APD was si gnificantly greater for the Ni++ group (11.8 +/- 14.3 msec) than for either the control group or rapid pacing group (both p less than or equal to 0.02 3). The dispersion of repolarization was increased only in the 4-AP group p ost rapid pacing (41.7 +/- 6.2 msec at baseline to 53.5 +/- 9.6 msec post p acing, p = 0.01). ERPs were unchanged in any of the 5 groups except for a d ecrease in left atrial ERP in the Niti group after rapid pacing (98 +/- 14 msec at baseline to 88 +/- 8 msec post rapid pacing, p = 0.005). Conclusions: In the isolated rabbit heart model: 1) atrial APD is shortened after rapid pacing; 2) the shortening of APD is attenuated by verapamil an d 4-AP but exaggerated by Ni++; 3) atrial conduction times are shortened in a direction specific manner after rapid pacing; and 4) shortening of ERP i n this model is measured only in the presence of Ni++. These findings sugge st that both L-type Ca++ and 4-AP sensitive channels may participate in atr ial electrical remodeling.