Prolonged vasospasm produced by the breakdown products of erythrocytes.

The cause of cerebral vasospasm has been generally attributed to the vasoconstrictive substances released from platelets. The role of extravasated erythrocytes in vasospasm has never been well analyzed. To elucidate this point, the basilar arteries of cats were exposed and subjected to topical application of various blood fractions in their fresh state and after prolonged incubation for 1 to 7 days. Incubation was done to test stability of the vasoconstrictors. Severe vasospasm was induced by application of fresh and incubated fractions of lysed erythrocytes. Fresh, intact erythrocytes had no vasoactivity, but by incubation they lysed and gained vasoconstrictors. Vasospasm induced by lysed erythrocytes both in their fresh state and after prolonged incubation never relaxed, and tended to increase in severity during observation up to 24 hours. Fresh serum and platelet-rich plasma had vasoconstrictors, but they were lost after incubation. Apparently platelet-induced vasoconstriction is of short duration and contributes only to the early phase of vasospasm. Later, 12 to 24 hours after hemorrhage, iron pigments released by lysis of extravasated erythrocytes (oxyhemoglobin or methemoglobin) irritate the arterial wall and induce prolonged vasospasm. It is emphasized that the study of cerebral vasospasm should be focused on the role of the breakdown products of extravasated erythrocytes.