Abstract 12866: Olmesartan Dissolves the Imbalance Between the Thrombotic and Fibrinolytic State in the Fibrillating Left Atrium in the Canine Model of Atrial Fibrillation
PURPOSE: The normal atrial endocardial cells control the local coagulation balance, expressing both antithrombotic molecules such as endothelial nitric oxide synthetase (eNOS), thrombomodulin (TM), and fibrynolytic molecules such as tissue plasminogen activator (t-PA). Atrial fibrillation (AF) may cause atrial endothelial dysfunction and lead to imbalance between the thrombotic and fibrinolytic state which contribute to thrombus formation in the fibrillating left atrium. In the present study, the expressions of thrombosis and fibrinolysis related molecules in the atrial tissue of the canine AF model were evaluated and the effect of olmesartan, an angiotensin receptor blocker, on their expressions was examined.
METHODS: The 27 dogs with atrial rapid stimulation devices were divided into 3 groups; 1) olmesartan group (n=9): 6-week pacing with olmesartan (2mg/kg/day), 2) control group (n=9): 6-week pacing without olmesartan, and 3) non-pacing group (n=9). At the end of the protocol, the atrial portions were excised and mRNA expressions of eNOS, TM, t-PA, von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) were evaluated by the real time RT-PCR (n=9 in each). The expression and localization of PAI-1 protein was evaluated by the western blot analysis and immuno-histochemical staining.
RESULTS: In the control group, vWF and t-PA were up-regulated and TM and eNOS were down-regulated only in the left atrium whereas PAI-1 was up-regulated in both atria. In the olmesartan group, these changes caused by rapid pacing except the down-regulation of t-PA were suppressed by olmesartan. The protein level of PAI-1 was up-regulated in both atria in the control group and it was suppressed by olmesartan. In the immuno-histochemical staining, the expression of PAI-1 was localized on the atrial surface and it was suppressed by olmesartan.
CONCLUSIONS: In the canine AF model, the changes in thrombotic and fibrinolytic state appeared in the atrial endothelium more prominently in the left atrium and these changes were suppressed by olmesartan. Angiotensin receptor blocker is considered to prevent the endothelial dysfunction by dissolving this imbalance between the thrombotic and fibrinolytic state.
- © 2011 by American Heart Association, Inc.