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

Background - 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. Methods and Results - 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 μmol/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±018% 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. Conclusions - 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.