Effects of subarachnoid hemorrhage and a thromboxane A2 synthetase inhibitor on intracranial prostaglandins.
The effects of subarachnoid hemorrhage (SAH) on intracranial prostaglandins (PGs) were studied in canines. Subarachnoid hemorrhage was produced by the "two hemorrhage" method. Basilar artery caliber and regional cerebral blood flow (rCBF) in the occipital cortex were reduced by 42% and 43% during delayed vasospasm, respectively. Once delayed vasospasm had developed, intravenous infusion of OKY-046, a selective inhibitor of thromboxane (TX) A2 synthetase, induced no significant change in angiographic vasospasm but caused a significant increase in rCBF. In delayed vasospasm, cortical levels of PGF2 alpha were significantly decreased, whereas plasma levels of PGF2 alpha and TXB2 in the transverse sinus were significantly increased. The intravenous infusion of OKY-046 in delayed vasospasm induced a significant increase in cortical PGF2 alpha and PGE in the occipital cortex, and caused a significant increase in plasma 6-keto-PGF1 alpha and a significant decrease in plasma TXB2 in the transverse sinus. In delayed vasospasm, decreased cortical levels of PGF2 alpha may reflect a decrease in rCBF and increased plasma PGF2 alpha and TXB2 levels may reflect enhancement of intravascular coagulation. These PGs have very strong and various biological activities. The results suggest that SAH induces complicated changes of intracranial PGs and OKY-046 can improve these pathological changes.
Yokota
M
M
Department of Neurosurgery, Hyogo College of Medicine, Japan.
Tani
E
E
Fukumori
T
T
Maeda
Y
Y
Yamaura
I
I
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000097:blood / Q000378:metabolism*; D004285:Dogs; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology*; D011458:Prostaglandins E / Q000097:blood / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D008689:Methacrylates; D011458:Prostaglandins E; D015237:Dinoprost; D013930:Thromboxane-A Synthase; C034364:ozagrel