Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation: role of nitric oxide.

Abstract

Platelet activation and decreased levels of nitrite and nitrate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course changes in plasma NOx levels and the expression of P-selectin on platelets after the onset of AF in a canine model and determined whether these parameters could be risk factors for silent cerebral infarction in patients with AF. AF was induced by rapid atrial pacing in the canine model of AF. Plasma NOx levels were significantly decreased and the levels of P-selectin on platelets and of neutrophil/platelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibition of NO synthesis increased the expression of P-selectin on platelets. Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 micromol/L) were significantly 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/platelet conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF. Multiple regression analysis revealed that increased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction. An irregular heart rate that is characteristic of AF appeared to blunt NO synthesis. The increased expression of P-selectin on platelets associated with the reduced NO levels was a risk factor for silent cerebral infarction in patients with AF.