Our previous report demonstrated that platelet cyclooxygenase activity and serum dopamine-β-hydroxylase activity in patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysms gradually increased, reaching a maximum value on Day 7 following the onset, coincided with the occurrence of vasospasm.
This study of human platelet cyclooxygenase, using an assay system measuring the thiobarbituric acid reaction, shows that dopamine-β-hydroxylase can trigger a rapid acceleration of cyclooxygenase activity to produce thromboxane A2 (TXA2).
These results suggest that an adrenergic mechanism plays an important role in the microcirculatory damage induced by lipid peroxidation during the occurrence of vasospasm following aneurysmal SAH.
The present study was further designed to find successful treatment for delayed spasm. Our previous study demonstrated that isosorbide dinitrate (1, 4: 3, 6-dianhydro-D-glucitol dinitrate, ISDN) was not only an inhibitor to both cyclooxygenase and dopamine-g-hydroxylase, but also a radical scavenger.
In our present study, topical application of ISDN (50 ng/ml) caused relief of experimental vasospasm in the cat basilar artery induced by 5 min topical application of incubated blood which obtained as a micture of an equivalent volume of blood and CSF incubated at 37°C for 3 days.
Topical application of ISDN (50 ng/ml) also caused relief of human constricted pial arteries on Day 3 following aneurysmal SAH. From the present study, ISDN is considered to relieve the microcirculatory damage due to vasospasm following aneurysmal SAH.
Our method of ISDN administration is to attach an ISDN adhesive tape preparation (40mg) on the chest, which is changed every 12 hours. The period of administration shall continue until the 14th day after occurrence of the intracranial aneurysm rupture.
In case of early operative intervention, 50ng/m/ ISDN 10 l is administered topically during the operation after clipping. If appearance or aggravation of ischemic symptoms is foreseen due to vasospasm, in spite of ISDN application, 50 ng/ml ISDN 10 ml is additionally administered into the cavity of the cerebrospinal fluid.
