NO hope for patients with atrial fibrillation.

Abstract

Atrial fibrillation (AF), either in its paroxysmal or chronic form, is associated with an increased risk of systemic embolization. Currently, the only effective therapy to reduce this risk is long-term systemic anticoagulation. Such treatment comes at a considerable cost; approximately 3% of patients with nonvalvular AF receiving an oral anticoagulant experience major bleeding events that require hospital admission.1 Considering the often devastating sequelae of cerebral emboli and the potentially life-threatening side effects of chronic anticoagulation, it is alarming how little is known about the mechanisms linking AF to intraatrial thrombus formation. Although several randomized, prospective, nonvalvular AF trials have examined putative hemostatic markers of increased risk for thrombosis,2 knowledge of the etiology and pathophysiology of AF-induced thromboembolic complications has remained sketchy. See p 2854 A new experimental study by Cai and co-workers3 published in this week’s issue of Circulation sets the stage for a better understanding of the mechanisms underlying thromboembolic events associated with AF. They discovered that 1 week of rapid pacing-induced AF in pigs is associated with a marked decrease in endothelial nitric oxide synthase (eNOS) expression, a reduction in production of nitric oxide (NO), and an increase in expression of plasminogen activator inhibitor 1 (PAI-1) in the left atrial endocardium. Because NO has antithrombotic properties, they concluded that loss of left atrial eNOS activity contributes to the thromboembolic events frequently associated with AF. As innovative and thought provoking as this study is, and as plausible as this conclusion seems in light of the well established antithrombotic action of NO, some caution in interpreting its results is necessary. First, we do not know whether the findings apply to other, clinically more relevant experimental models of AF, such as chronic AF caused by mitral valve regurgitation4 or AF associated with chronic heart failure.5 Measurements …