INCREASED EXPRESSION OF P-SELECTIN ON PLATELETS IS A RISK FACTOR FOR SILENT CEREBRAL INFARCTION IN PATIENTS WITH ATRIAL-FIBRILLATION - ROLEOF NITRIC-OXIDE

Background-Platelet activation and decreased levels of nitrite and nit rate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course ch anges in plasma NOx levels and the expression of P-selectin on platele ts after the onset of AF in a canine model and determined whether thes e parameters could be risk factors for silent cerebral infarction in p atients with AF. Methods and Results-AF was induced by rapid atrial pa cing in the canine model of AF, Plasma NOx levels were significantly d ecreased and the levels of P-selectin on platelets and of neutrophil/p latelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibiti on of NO synthesis increased the expression of P-selectin on platelets . Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 mu mol/L) were signi ficantly lower in 25 patients with AF compared with age- (+/-2 years) and sex-matched control subjects. Conversely, the levels of P-selectin on platelets (7.6+/-0.8% versus 4.8+/-0.7%) and of neutrophil/platele t conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF, Multiple regression analysis revealed that incre ased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction. Conclusions-An irregula r heart rate that is characteristic of AF appeared to blunt NO synthes is. The increased expression of P-selectin on platelets associated wit h the reduced NO levels was a risk factor for silent cerebral infarcti on in patients with AF.