ELECTRICAL REMODELING DUE TO ATRIAL-FIBRILLATION IN CHRONICALLY INSTRUMENTED CONSCIOUS GOATS - ROLES OF NEUROHUMORAL CHANGES, ISCHEMIA, ATRIAL STRETCH, AND HIGH-RATE OF ELECTRICAL ACTIVATION

Background Recently, we developed a goat model of chronic atrial fibri llation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present stud!: wa s to evaluate the role of (1) the autonomic nervous system, (2) ischem ia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid at rial pacing in this process of electrical remodeling. Methods and Resu lts Twenty-five goats were chronically instrumented with multiple epic ardial atrial electrodes, Infusion of atropine (1.0 mg/kg; n=6) or pro pranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K-ATP(+) channels by glibenclamid e (10 mu mol/kg; n=6) slightly increased the AFI from 95 +/- 4 to 101 +/- 5 ms, but AFI remained considerably shorter than during acute AF ( 145 ms). Glibenclamide had no significant effect on AERP after electri cal cardioversion of AF (69 +/- 14 versus 75 +/- 15 ms). Volume loadin g by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks o f AF (n=6), but ANF infusion (0.1 to 3.1 mu g/min, n=4) did not shorte n AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively short ened AERP from 134 +/- 10 to 105 +/- 6 ms and inversed its physiologic al rate adaptation. Conclusions Electrical remodeling by AF is not med iated by changes in autonomic tone, ischemia, stretch, or ANF. The hig h rate of electrical activation itself provides the stimulus for the A F-induced changes in AERP.