(Circulation. 1997;96:3710-3720.)
© 1997 American Heart Association, Inc.
Articles |
Electrical Remodeling due to Atrial Fibrillation in Chronically Instrumented Conscious Goats
Roles of Neurohumoral Changes, Ischemia, Atrial Stretch, and High Rate of Electrical Activation
From the Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands.
Correspondence to Prof Dr M.A. Allessie, Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Background Recently, we developed a goat model of chronic atrial fibrillation (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 study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling.
Methods and Results Twenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K+ATP channels by glibenclamide (10 µmol/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 electrical cardioversion of AF (69±14 versus 75±15 ms). Volume loading 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 of AF (n=6), but ANF infusion (0.1 to 3.1 µg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134±10 to 105±6 ms and inversed its physiological rate adaptation.
Conclusions Electrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.
Key Words: atrium • arrhythmia • fibrillation • remodeling • reentry
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