Increased thromboxane biosynthesis in patients with acute cerebral ischemia.
OBJECTIVE
Clinical and experimental studies suggest that platelets have a major role in the pathogenesis of cerebral ischemia. However, ex vivo both platelet aggregation studies and measurements of platelet-derived products in patients with cerebral ischemia have shown inconsistent results. The present study was designed to resolve this inconsistency.


METHODS
We have measured the urinary excretion of a thromboxane metabolite, 11-dehydro-thromboxane B2, by a previously validated radioimmunoassay technique in 51 patients with acute cerebral ischemia who had experienced either a transient ischemic attack (14 patients) or an ischemic stroke (37 patients) and in 20 control patients with nonvascular neurological disorders. The median time between the onset of symptoms and urine sampling was 24 hours (range, from 2 hours to 8 days).


RESULTS
The excretion rate of immunoreactive 11-dehydro-thromboxane B2 ranged between 39 and 478 pmol/mmol creatinine in patients with a transient ischemic attack and between 23 and 5,916 pmol/mmol creatinine in stroke patients, with 29% (p = 0.18) and 51% (p = 0.004) of the urine samples, respectively, exceeding the upper limit of the control samples (251 pmol/mmol creatinine [mean +/- 2 SD]) (p = 0.01). In stroke patients, metabolite excretion was not related to the type (cortical or "lacunar") or site of cerebral infarction. Low-dose aspirin (50 mg per day for 7 days) reduced the urinary excretion by approximately 85% in 11 consecutive stroke patients.


CONCLUSIONS
We conclude that 1) episodes of enhanced thromboxane biosynthesis are detected infrequently in patients with a transient ischemic attack, 2) aspirin-suppressible episodes of increased thromboxane formation can be detected during the early phase of acute ischemic stroke, and 3) this finding may provide a rationale for testing the efficacy and safety of this drug in this setting.
Koudstaal
P J
PJ
Department of Neurology, University Hospital Rotterdam, The Netherlands.
Ciabattoni
G
G
van Gijn
J
J
Nieuwenhuis
H K
HK
de Groot
P G
PG
Sixma
J J
JJ
Patrono
C
C
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism; D002545:Brain Ischemia / Q000652:urine*; D002561:Cerebrovascular Disorders / Q000652:urine; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000652:urine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine
D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2