Etiology and Treatment of Prolonged Vasospasm

According to the Speden's method, a spirally cut strip of the basilar artery of a dog was mounted in a bath filled with artificial CSF, and vasoactivity of fresh and aged serum, whole blood and blood-CSF mixture upon the isolated artery were tested. Contraction of artery produced by serum was most obvious in the fresh sample and diminished quickly as aging continued. Thus serum aged over 4 days were essentially non-vasoactive. Also it was completely abolished by adding methysergide, a serotonin antagonist. On the other hand, vasoactivity found in supernatants of the incubated whole blood and blood-CSF mixture progressively increased as incubation continued, reaching its peak after approximately 7 days of incubation. When the aged whole blood or aged blood-CSF mixture, particularly the latter, was applied, a tonic tention superimposed with phasic contraction of the isolated artery developed and lasted for several hours. Contraction was further enhanced markedly under the hypoxic condition produced by the cessation of continuous O2-supply into the reaction medium. Supernatants of blood-CSF mixture incubated for 7 days at 37°C was passed through a column of sephadex G-100. Vasoactive substance existed specifically at the peak III which demonstrated positive ninhydrin reaction. When peak III, thus isolated, was introduced into the basal cistern of the dog marked vasospasm at the circle of Willis and basilar artery developed and lasted over 2 weeks. Further biochemical analysis of peak III using CM cellulose ion exchange resin and disc electrophoresis, demonstrated that the vasoactive property lay in the polypeptides closely allied to oxyhemoglobin or oxyhemoglobin itself. Haptoglobin, a normal constituent of serum, is known to combine with hemoglobin to form a stable hemoglobin-haptoglobin compound. Following the next series of experiments of either in vitro or in vivo conditions, it was demonstrated that the hemoglobin induced vasospasm was greatly abolished by the addition of haptoglobin. Clinical application of haptoglobin upon the spastic cerebral artery around the ruptured aneurysm were found to be very encouraging.