(Stroke. 1997;28:1557-1563.)
© 1997 American Heart Association, Inc.
Articles |
Platelet Activation and Lipid Peroxidation in Patients With Acute Ischemic Stroke
From the Department of Neurology, University Hospital Rotterdam, Netherlands (F. van K., D.W.J.D., P.J.K.); the Department of Pharmacology, Catholic University School of Medicine, Rome, Italy (G.C.); and the Department of Pharmacology, University of Chieti "G. D'Annunzio," Chieti, Italy (C.P.).
Correspondence to Fop van Kooten, MD, Department of Neurology, University Hospital Rotterdam Dijkzigt, 40 Dr Molewaterplein, 3015 GD Rotterdam, Netherlands. E-mail:vankooten{at}neuro.fgg.eur.nl
Background and Purpose Both platelet activation and
lipid peroxidation are potential sources of vasoactive eicosanoids that
can be produced via the cyclooxygenase pathway, ie,
thromboxane (TX) A2, or by free
radical–catalyzed peroxidation of arachidonic acid,
ie, isoprostanes. We investigated the biosynthesis of TXA2
and F2-isoprostanes, as reflected by the urinary excretion
of 11-dehydro-TXB2 and 8-epi-prostaglandin (PG)
F2
, respectively, in 62 consecutive patients
(30 men, 32 women; mean age, 67±14 years) with acute ischemic
stroke.
Methods At least two consecutive 6-hour urine samples were obtained during the first 72 hours after onset of symptoms. Urinary eicosanoids were measured by previously described radioimmunoassays.
Results Repeated periods of enhanced
thromboxane biosynthesis were found in 52% of patients.
Urinary 11-dehydro-TXB2 averaged 221±207 (mean±SD; n=197;
range, 13 to 967) pmol/mmol creatinine in 30 patients
treated with cyclooxygenase inhibitors
(mostly aspirin) at the time of study versus 392±392 (n=186; range, 26
to 2533) in 32 untreated patients (P<.001). The
corresponding values for 8-epi-PGF2
excretion were 74±42 (range, 14 to 206) and 83±65 (range, 24 to 570)
pmol/mmol creatinine (P>.05). The correlation
between the two metabolites was moderate in both untreated patients
(r=.41, P<.001) and patients with
cyclooxygenase inhibitors
(r=.31, P<.001). In a multiple regression
analysis, increased thromboxane production
was independently associated with severity of stroke on admission,
atrial fibrillation, and treatment with
cyclooxygenase-inhibiting drugs.
Conclusions We conclude that during the first few days after an acute ischemic stroke (1) platelet activation occurs repeatedly in a cyclooxygenase-dependent fashion; (2) platelet activation is not associated with concurrent changes in isoprostane biosynthesis; (3) platelet activation is independently associated with stroke severity and atrial fibrillation; and (4) isoprostane biosynthesis is largely independent of platelet cyclooxygenase activity.
Key Words: cerebral ischemia • lipid peroxidation • platelet activation • thromboxanes
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