Effect of selective inhibitor of thromboxane A2 synthetase on experimental cerebral vasospasm.
Experimental cerebral vasospasm was induced in the canine basilar artery by an intracisternal injection of fresh autogenous arterial blood. Delayed vasospasm was defined as a reduction to less than 75% of the caliber of control basilar artery 5 days after the intracisternal blood injection. A selective inhibitor of thromboxane A2 synthetase, sodium(E)-3-[4-(3-pyridylmethyl) phenyl]-2-methyl-2-propenoate, was infused intravenously for 1 or 2 hrs at 50 micrograms/kg/min in normal animals exhibiting vasospasm. Angiographic evidence of cerebral vasospasm was not reversed. Mean regional cerebral blood flow was not significantly increased in normal and vasospastic animals, but a mean difference of regional cerebral blood flow was significantly increased only in vasospastic animals. Mean arterial blood pressure and pulse rate were not seriously changed in normal and spastic animals. Another selective thromboxane A2 synthetase inhibitor, (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate, showed a similar effect on the caliber of the basilar artery, regional cerebral blood flow, blood pressure, and pulse rate, in vasospastic animals. Venous blood was taken from the internal jugular vein, and the mean platelet aggregation induced by 10 micrograms/ml of collagen was inhibited by the infusion of either selective inhibitor at 50 micrograms/kg/min for 2 hrs. However, mean platelet aggregation rates in vasospastic animals before and after treatment with either selective inhibitor were not significantly different to those in normal animals.
D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008689:Methacrylates / Q000008:administration & dosage; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008689:Methacrylates; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase; C034364:ozagrel