Platelet activation and lipid peroxidation in patients with acute ischemic stroke.
OBJECTIVE
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 alpha 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 alpha 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.
van Kooten
F
F
Department of Neurology, University Hospital Rotterdam, Netherlands. vankooten@neuro.fgg.eur.nl
Ciabattoni
G
G
Patrono
C
C
Dippel
D W
DW
Koudstaal
P J
PJ
D000208:Acute Disease; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000378:metabolism / Q000652:urine; D002545:Brain Ischemia / Q000097:blood* / Q000378:metabolism* / Q000652:urine; D002561:Cerebrovascular Disorders / Q000097:blood* / Q000378:metabolism* / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015237:Dinoprost / Q000652:urine; D005260:Female; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D012016:Reference Values; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
D016861:Cyclooxygenase Inhibitors; D008054:Lipid Peroxides; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D015237:Dinoprost