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From the First Department of Medicine (T.M., M.K., H.A., T. Kuzuya, T.
Kurotobi, M.H.), Osaka University School of Medicine, Suita, Japan; Division
of Cardiology (S.S., M.F., N.H.), Osaka Prefectural Hospital, Osaka, Japan;
and Division of Cardiology (Y.K.), Osaka National Hospital, Osaka, Japan.
Correspondence to Masafumi Kitakaze, MD, The First Department of Medicine, Osaka University School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565, Japan. E-mail kitakaze{at}medone.med.osaka-u.ac.jp
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±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.
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.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Increased Expression of P-Selectin on Platelets Is a Risk Factor for Silent Cerebral Infarction in Patients With Atrial Fibrillation
Role of Nitric Oxide
Key Words: fibrillation • endothelium-derived factors • risk factors • brain • infarction
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