Effects of Cilazapril on atrial electrical, structural and functional remodeling in atrial fibrillation dogs.
OBJECTIVE
The effects of angiotensin-converting enzyme inhibitor on long-term atrial electrophysiologic and structural remodeling are still unclear. The purpose of this study is to investigate the effects of Cilazapril on atrial electrical, structural, and functional remodeling in atrial fibrillation (AF) dogs induced by chronic rapid atrial pacing.


METHODS
Twenty dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), and Cilazapril group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group and Cilazapril group were paced at 400 beats per minute for 6 weeks. The dogs in Cilazapril group received Cilazapril (0.5 mg x kg(-1) x d(-1)) 1 week before rapid atrial pacing until pacing stop. Before and after 6-week rapid atrial pacing, atrial effective refractory period (AERP) at 8 sites, AERP dispersion, intraatrium conduction time, inducibility, and duration of AF were measured. Transthoracic and transesophageal echocardiographic examinations included left atrium (LA) maximal volume, LA minimal volume, LA ejection fraction, left atrial appendage (LAA) maximal volume, LAA minimal volume, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were performed. Atrial collagen volume fraction was analyzed by Masson staining.


RESULTS
After 6-week rapid atrial pacing, although there was no significant difference in AERP shortening and AERP rate adaptation reduction between the control group and the Cilazapril group, the inducibility and duration of AF were found to be dramatically lower in the Cilazapril group than those in the control group (AF inducibility, 65.7% vs 95.7%, P < .05; AF duration, 531.5 +/- 301.2 vs 1432.2 +/- 526.5 s, P < .01). The post-tachycardia intraatrium conduction times after 6 weeks with Cilazapril were significantly shorter than those in the control group. Cliazapril could partially prevent AERP dispersion increase induced by chronic rapid atrial pacing. Compared with the control group, the LA and LAA volumes were significantly smaller; LA ejection fraction, LAA ejection fraction, LAA maximal forward flow velocity, and LAA minimal backward flow velocity were dramatically higher in the Cilazapril group. The Cilazapril group had a significantly lower percentage of interstitial fibrosis than the control group.


CONCLUSIONS
Cilazapril can suppress structural and functional remodeling and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs.
Li
Yue
Y
Cardiovascular Department, the First Clinical Hospital, Harbin Medical University, Harbin, PR China.
Li
Weimin
W
Yang
Baofeng
B
Han
Wei
W
Dong
Deli
D
Xue
Jingyi
J
Li
Baoxin
B
Yang
Shusen
S
Sheng
Li
L
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D017315:Cilazapril / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006325:Heart Atria / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000503:physiopathology*; D006329:Heart Conduction System / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D017315:Cilazapril