Effects of Angiotensin-II Receptor Blocker on Inhibition of Thrombogenicity in a Canine Atrial Fibrillation Model.
OBJECTIVE
Angiotensin-II receptor blockers (ARBs) are known to reduce the development of atrial fibrillation (AF) through reverse-remodeling. However, the effect of ARBs on thrombogenicity in AF remains unknown.


METHODS
Twelve dogs were assigned to control (n=4), ARB (candesartan cilexitil 10 mg/kg/day p.o., 12 weeks; n=4), or sham (n=4) groups. Sustained AF was induced by rapid atrial pacing. Both arterial and venous serum levels of tissue inhibitor of matrix metalloproteinase-1, von Willebrand factor, P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and during AF (0, 4, and 12 weeks) with enzyme-linked immunosorbent assay. Biopsies from both atria including the appendages were performed to semi-quantitatively assess endocardial and myocardial fibrosis after 12 weeks.


RESULTS
The serum levels of bio-markers were not significantly different at baseline or during AF between the control and the candesartan groups. The levels were not significantly different over time, but there was a trend toward a decrease in arterial VCAM-1 from 4 to 12 weeks in the candesartan group compared to the control group. The grades of endocardial fibrosis after 12 weeks but not those of myocardial fibrosis were slightly reduced in the candesartan group compared to the control group.


CONCLUSIONS
This study did not show that the ARB candesartan significantly reverses thrombogenicity or fibrosis during AF. Future studies using a larger number of subjects are warranted to determine the therapeutic effect of renin-angiotensin-aldosterone system blockade on prothrombogenic processes in AF.
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Jong-Il
JI
Choi
Department of Thoracic and Cardiovascular Surgery, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Jae Seung
JS
Jung
Kim Min Kyung's Pathology Clinic, Seoul, Korea .
Min Kyung
MK
Kim
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Jaemin
J
Sim
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Jin Seok
JS
Kim
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Hong Euy
HE
Lim
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Sang Weon
SW
Park
Division of Cardiology, Department of Internal Medicine, Korea University College of Medicine, Korea University Medical Center, Seoul, Korea .
Young-Hoon
YH
Kim
Angiotensin II; Atrial fibrillation; Biological markers; Fibrosis; Thromboembolism