Iloprost in Experimental Cerebral Ischemia

  • J. Cahn
  • M. G. Borzeix

Abstract

End-products of arachidonic acid cascade are known to play a role in platelet aggregation and may also be involved in the pathogenesis of various cerebral dis-eases related to ischemia. The transformation of arachidonic acid into thromboxane A2 (TXA2) occurs via the production of intermediate products called endoperoxides. Apart from the effects of TXA2, it is now well known that healthy vessel walls readily transform endoperoxides into an unstable substance which is a potent vasodilator and inhibitor of platelet aggregation. This compound, originally called PGX by Moncada et al. [17, 18], and Gryglewski et al. [12], has been renamed prostacyclin or PGI2 [16]. Its pharmacological properties led us to hypothesize that PGI2 and some stable prostacyclin analogues, such as Iloprost, may be helpful in improving the postischemic disease in which platelet aggregation and vascular spasms are particularly involved, as well as in reducing the seconday decrease in cerebral blood flow called “delayed hypoperfusion” which succeeds the initial reactive hyperemia [14]. The aim of this study has been to investigate on one hand the curative effect of Iloprost on the neurologic deficit, the electrolyte unbalance and the impairment of brain function which develop in the subacute period (3 days) following a transient cerebral oligemia in the rat [3, 4]; and on the other hand its effect upon the hemodynamic and metabolic consequences of a transient cerebral ischemia in the dog over the acute phase (2 h) following subtotal occlusion of carotid and vertebral arteries [7].

Keywords

Peroxide Sucrose Ischemia Prostaglandin Atropine 

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References

  1. 1.
    Allen GC (1985) Cerebral arterial spasm. Controlled trials of Nimodipine in subarachnoid hemorrhage patients. In: Betz E, Deck K, Hoffmeister F (eds) Nimodipine. Pharmacological and clinical properties. Schattauer, Stuttgart, pp 379–385Google Scholar
  2. 2.
    Antonis A (1965) Semiautomated method for the colorimetric determination of plasma free fatty acids. J Lipid Res 6: 307–312PubMedGoogle Scholar
  3. 3.
    Borzeix MG (1983) Le syndrome post-oligémique chez le rat. Un modèle d’atteinte cérébrale chronique. Cire Métab Cerveau 1: 63–79Google Scholar
  4. 4.
    Borzeix MG (1984) Drug effect in an experimental stroke resulting from a transient cerebral oligemia. Maladies et Médicaments. Drugs Dis 1 (3): 44–53Google Scholar
  5. 5.
    Burešova O, Bureš J, Bohdanecky Z, Weiss T (1964) Effect of atropine on learning, extinction, retention and retrieval in rats. Psychopharmacologia (Berlin) 5: 255–263CrossRefGoogle Scholar
  6. 6.
    Cahn J (1985) The effects of Ca+ + antagonists in cerebrovascular diseases: an increase in CBF or a blockade of Ca+ + entry? In: Betz E, Deck K, Hoffmeister F (eds) Nimodipine. Pharmacological and clinical properties. Schattauer, Stuttgart, pp 137–140Google Scholar
  7. 7.
    Cahn J, Borzeix MG (1984) Corrélations entre la PO2 corticale, l’extraction en oxygène et le débit sanguin dans l’ischémie cérébrale aiguë chez le chien. Possibilités Thérapeutiques. Maladies et Médicaments. Drugs Dis 1 (1): 50–64Google Scholar
  8. 8.
    Cahn J, Herold M, Henon C (1968) Réanimation hépatique par des substances à visée métabolique. In: Larcan A (ed) Problèmes de réanimation, 5ème série, SPEI, Paris, pp 803–826Google Scholar
  9. 9.
    Farber JL (1981) The role of calcium in cell death. Life Sci 29: 1289–1295PubMedCrossRefGoogle Scholar
  10. 10.
    Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol 17: 149–166PubMedCrossRefGoogle Scholar
  11. 11.
    Grote J, Kreusher H, Schubert R, Ross HJ (1971) Investigation on the influence of PaO2 and PaCO2 on the regulation of cerebral blood flow in dogs. In: Ross-Russel RW (ed) Brain and blood flow. Pitman, London, pp 200–204Google Scholar
  12. 12.
    Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR (1976) Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685–713PubMedCrossRefGoogle Scholar
  13. 13.
    Hass WK (1981) Beyond cerebral blood flow, metabolism and ischemic thresholds: an examination of the role of calcium in the initiation of cerebral infarction. In: Meyer JS, Lechner H, Reivich M, Ott ED, Aranibar A (eds) Cerebral vascular disease, vol 3. Excerpta Medica, Amsterdam, pp 3–17Google Scholar
  14. 14.
    Hossmann KA, Lechtape-Grüter H, Hossmann V (1973) The role of cerebral blood flow for the recovery of the brain after prolonged ischemia. Z Neurol 204: 281–299PubMedCrossRefGoogle Scholar
  15. 15.
    Irwin S (1968) Comprehensive observational assessment: la. A systematic quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia (Berlin) 13: 222–257CrossRefGoogle Scholar
  16. 16.
    Johnson RA, Morton DR, Kinner JH, Gorman RR, McGuire JC, Sun FF, Whittaker N, Bunting S, Salmon J, Moncada S, Vane JR (1976) The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915–928PubMedCrossRefGoogle Scholar
  17. 17.
    Moncada S, Gryglewski RJ, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665PubMedCrossRefGoogle Scholar
  18. 18.
    Moncada S, Gryglewski RJ, Bunting S, Vane JR (1976) A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins 12: 715–733PubMedCrossRefGoogle Scholar
  19. 19.
    Ray Sarkar BC, Chauhan VPS (1967) A new method for determining micro quantities of calcium in biological materials. Anal Biochem 20: 155–166PubMedCrossRefGoogle Scholar
  20. 20.
    Renhcrona S, Westerberg E, Akesson B, Siesjo BK (1982) Brain cortical fatty acids and phospholipids during and following complete and severe incomplete ischemia. J Neurochem 38: 84–93CrossRefGoogle Scholar
  21. 21.
    Shay J (1973) Does calcium influx into ischemic cells stop ADP phosphorylation? Lancet 2: 1392PubMedCrossRefGoogle Scholar
  22. 22.
    Siesjo BK (1981) Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab 1: 155–185PubMedCrossRefGoogle Scholar
  23. 23.
    van Zwieten PA (1985) Calcium antagonists — terminology, classification and comparison. Arzneimittelforsch/Drug Res 35 (1): 298–301Google Scholar
  24. 24.
    Wolfe LS (1982) Eicosanoids: prostaglandins, thromboxanes, leukotrienes and other derivatives of carbon-20 unsaturated fatty acids. J Neurochem 38: 1–14PubMedCrossRefGoogle Scholar
  25. 25.
    Yoshida S, Inoh S, Asano T, Sano K, Kubota M, Shimazaki H, Ueta N (1980) Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. J Neurosurg 53: 323–331PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1987

Authors and Affiliations

  • J. Cahn
    • 1
  • M. G. Borzeix
    • 1
  1. 1.Department of Experimental Therapy — SIR internationalMontrougeFrance

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