Experimental study on pathogenesis and treatment of cerebral vasospasm

Part 1. Effects of thromboxane A₂ synthetase inhibitor (OKY-046) on experimental cerebral vasospasm

Abstract

The effects of a thromboxane A₂ 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 incubated at 37°C 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 hypotension (n=5). In 3 control cats, r-CBF decreased in relation to systemic hypotension. These results indicate that thromboxane A₂ 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.