Experimental Study of Cerebral Vasospasm Induced by Serotonin and Oxyhemoglobin in Subarachnoid Hemorrhage

Abstract

To clarify the mechanism of cerebral vasospasm induced by serotonin (5-HT) and oxyhemoglobin (OxyHb), the authors studied the roles of vasoactive pros taglandins (PGs) and free radicals in the cerebral vascular wall of rabbits. At first, they measured the 5-HT level in whole blood plus cerebrospinal fluid (CSF) and in platelet-rich plasma (PRP) plus CSF by fluorescence following the incubation at 37°C for zero to six days. The 5-HT in whole blood plus CSF did not significantly diminish for up to five days (p < 0.05), but in PRP plus CSF it markedly decreased within twenty-four hours (p < 0.01).

The authors prepared 49 rabbits, divided into four groups: a nontreated (control) group and three groups treated with 5-HT, with OxyHb, and with free radical scavengers plus OxyHb, respectively. After treating the vessels with 5-HT or OxyHb, they measured levels of 6-keto-PGF₁α and thromboxane B₂ (TXB₂), the stable metabolites of prostacyclin (PGI₂) and TXA₂, respectively, with PGE₂ in vessels by radioimmunoassay. Vascular lipid peroxidation (LPO) was also measured by fluorescence. In the nontreated group, the level of 6-keto- PGF₁α was significantly higher in the basilar vessels than that of any peripheral vessels (p < 0.01).

In the group treated with 5-HT, 5-HT contracted both basilar and femoral arteries, but there was no significant change in levels of 6-keto-PGF₁α, TXB₂ , PGE₂, and LPO. Vasospasm induced by 5-HT is not specific to the cerebral artery and does not depend on PGs and LPO. In the group treated with OxyHb, however, OxyHb induced severe vasospasm in the basilar vessel alone, where LOP was highly increased (p < 0.01) and 6-keto-PGF₁ α markedly decreased

(p < 0.01), but there was no significant change in TXB₂ and PGE₂. OxyHb did not induce femoral arterial spasm. But the LPO content was increased (p < 0.01), and there was no change in the levels of 6-keto-PGF₁α, TXB₂, and PGE₂. These results disclose that cerebral vasospasm induced by OxyHb may depend on the high level of PGI₂, a vasodilator, in the vascular wall.

When various free radical scavengers were mixed with OxyHb, only manni tol, which is a hydroxy radical scavenger, could inhibit cerebral vasospasm in duced by OxyHb and elevate the level of 6-keto-PGF₁α in the arterial wall. Therefore, the mechanism of cerebral vasospasm induced by OxyHb depends on the hydroxy radical, which inhibits PGI₂ metabolism.