Cerebral platelet thromboembolism and thromboxane synthetase inhibition.
Platelet aggregating sodium arachidonate was slowly infused into the internal carotid artery (1 mg, 100 microliters, 1 microliter/s) of nitrous oxide anesthetized rats. The electroencephalographic activity recorded by a Cerebral Function Monitor from the injected hemisphere was reduced within minutes. The somatosensory evoked responses to contralateral electrical stimulation of the whisker area were eliminated on the same side in most cases when measured five and fifteen minutes after the infusion. The brain was frozen in situ with liquid nitrogen after fifteen minutes. Regional tissue analysis showed ipsilateral derangement of the cerebral energy state and increased lactate levels. Pretreatment with the platelet antiaggregating thromboxane synthetase inhibitor OKY-1581 (Sodium-3-4-(3-pyridylmethyl)phenyl-2-methyl-acrylate), 30 mg/kg i.v., fifteen minutes before the sodium arachidonate infusion prevented cerebral energy failure and elimination of the sensory evoked responses.
D000179:Acrylates / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004569:Electroencephalography; D004734:Energy Metabolism; D005073:Evoked Potentials, Somatosensory; D006493:Heparin / Q000494:pharmacology; D002542:Intracranial Embolism and Thrombosis / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000179:Acrylates; D001095:Arachidonic Acids; D008689:Methacrylates; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D006493:Heparin; D013930:Thromboxane-A Synthase