Experimental study on pathogenesis and treatment of cerebral vasospasm Part 2. Effects of PGI2 analogue, thromboxane A2 synthetase inhibitor and Ca blocker on experimental delayed spasm models

The effects of a PGI2 analogue (OP-41483), a thromboxane A2 synthetase inhibitor (OKY-046) and a Ca blocker (nifedipine) on the diameter of constricted basilar arteries and on the regional cerebral blood flow (r-CBF) in the brain stem were investigated in the cat delayed spasm model. The experiment was performed three days (72 hours) after artificial subarachnoid hemorrhage. The basilar artery was exposed transclivally, and more advanced vasospasm was produced by topical application of a lysed erythrocyte solution for 5 to 6 hours which domonstrated no more vascular dilatation even by topical application of papaverine hydrochloride (0.01mg/ml). In the delayed spasm model, the intravenous administration of neither OP-41483 (8μg/kg), OKY-046 (60mg/kg) nor nifedipine (0.003mg/kg) affected the vascular diameter. OP-41483 increased r-CBF in the brain stem in 3, and nifedipine increased it in 4 out of the 5 studied delayed spasm models, whereas OKY-046 never increased r-CBF (n=5). There was no significant difference in the amount of fatty acids including arachidonic acid between normal and constricted arteries. This study suggested that thromboxane A2 is not the major factor of cerebral vasospasm and OKY-046 might not be effective on vascular diameter or r-CBF at the late spasm stage. However, the PGI2 analogue (OP-41483) and Ca blocker (nifedipine) may be effective in increasing r-CBF even at the late spasm stage