脳血管攣縮の発生機序と治療に関する実験的研究 第1編 実験的脳血管攣縮に対するThromboxane A(2)(TxA(2))合成酵素阻害剤(OKY-046)の効果

The effects of a thromboxane A(2) synthetase inhibitor (OKY-046: sodium (E)-3-[4-(1-imidazolylmethyl)]-2-propenoate) on the diameter of normal and constricted basilar arteries and on the regional cerebral blood flow (r-CBF) in the brain stem after experimental subarachnoid hemorrhage (SAH) were investigated in 27cats. The basilar artery was exposed transclivally, and the change in its diameter was studied by serial photographs. Both normal and constricted basilar arteries showed only slight dilatation after an intravenous injection of OKY-046 (30mg/kg, 60mg/kg). Mean arterial blood pressure (MABP) decreased dose dependently with the administration of OKY-046. Exprimental SAH was produced by an intracisternal injection of 3ml of fresh autologous arterial blood. Three days later, the basilar artery was exposed transclivally, and an advanced prolonged vasospasm was produced by topical application of a blood-CSF mixture incubatesd at 37℃ for 3days. The change in r-CBF in the brain stem was measured continuously by the heat clearance method before, during and after intravenous administration of OKY-046 (30mg/kg, 60mg/kg). The changes of r-CBF in cats with experimental SAH (n=9) were divided into three types: no change in r-CBF (n=3), a transient decrease in r-CBF related to the decrease in MABP (n=1) and an increase in r-CBF in spite of systemic lypotension (n=5). In 3 control cats, r-CBF decreased in relation to systemic hypotension. These results indicate that thromboxane A(2) is not the major factor of cerebral vasospasm. However, OKY-046 which has been known to inhibit platelet aggregation and to prevent vascular constriction, might be useful in the prophylaxis and treatment of ischemic symptoms in patients with cerebral vasospasm.