[Intracranial administration of tissue plasminogen activator and its important factors involved concerning the pH and osmotic pressure]


Journal Article (Academic article)

Tissue plasminogen activator (t-PA) is expected to be used for cisternal drainage in subarachnoidal hemorrhage, for dissolving of the residual hematoma after stereotactic evacuation of a cerebral hematoma, and for regional intraarterial injection therapy for occlusion of the primary cerebral artery. This is because the drug exerts a very potent and immediate dissolving-effect on a hematoma when it is locally administered. However, the solubility of t-PA is rapidly decreased at pH 5 or more. At pH 7 or more, precipitation of crystals is observed when the concentration of t-PA exceeds 20 x 10(4) IU/ml. The pH of the t-PA general-purpose solution (for intravenous injection) is adjusted at 4.6 to 4.8 because of its solubility and stability, and the osmotic pressure is also increased with an increase in concentration of t-PA. When the concentration of t-PA is 750 x 10(4) IU/ml, the osmotic ratio is 30 and the pH is 4.82. These features suggest that a locally administered t-PA solution at high concentration may induce meningeal irritation leading to headache and vomiting, and exacerbation of symptomatic cerebral vasospasm when it is used for cisternal drainage. Furthermore, the t-PA solution administered intraarterially at high concentration may induce adverse effects such as dessiocyte and echinocyte deformation of erythrocytes and the sludging phenomenon of leukocytes in the cerebral microcirculation, and a sensation of fever and pain upon injection. Therefore, the dose and method of administration of the t-PA for local intracranial use should be determined by taking into consideration its pH and osmotic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Duke Authors

Cited Authors

  • Ebina, K; Shimizu, T; Yoshizumi, T; Iwabuchi, T

Published Date

  • September 1, 1991

Published In

Volume / Issue

  • 19 / 9

Start / End Page

  • 817 - 823

International Standard Serial Number (ISSN)

  • 0301-2603


  • Japanese