Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction.
Effects of enalapril on a canine model of atrial pacing-induced atrial fibrillation (AF) with rapid ventricular responses were determined.


METHODS
Four weeks of atrial rapid pacing was performed on twenty-four beagles pretreated with placebo (Group I, n = 14) or enalapril 1 mg/kg (Group II, n = 10). Atrial effective refractory period (ERP), P-wave width, duration of AF, and left ventricular ejection fraction (LVEF) were evaluated every week. AF cycle length was determined by spectral analyses of fibrillation waves. Quantitative analysis of histology was added.


RESULTS
After 4 weeks of pacing, P-wave width was longer in Group I than in Group II, and the duration of induced AF was significantly longer in Group I (59.6 +/- 66.3 seconds) than in Group II (3.6 +/- 3.4 seconds, P < 0.05). AF cycle length was longer in Group I than in Group II despite similar shortening of atrial ERP. Mean ventricular rate during rapid atrial pacing was not different between the two groups. LVEF similarly decreased in both groups. Interstitial fibrosis and expression of connexin43 was greater in Group I than in Group II (interstitial fibrosis, 9.2 +/- 8.4 versus 1.9 +/- 2.1%, P < 0.05; connexin43, 5.3 +/- 2.2 versus 1.1 +/- 1.1%, P < 0.05).


CONCLUSIONS
Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis, connexin43 over-expression and conduction delay.
Sakabe
Masao
M
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Fujiki
Akira
A
Nishida
Kunihiro
K
Sugao
Masataka
M
Nagasawa
Hidehiko
H
Tsuneda
Takayuki
T
Mizumaki
Koichi
K
Inoue
Hiroshi
H
D000818:Animals; D001281:Atrial Fibrillation / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D002304:Cardiac Pacing, Artificial; D018031:Connexin 43 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005355:Fibrosis; D008297:Male; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
D018031:Connexin 43; D004656:Enalapril