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The Role of Calcium Entry Blockers in Brain Ischemia

  • Petter Andreas Steen

Abstract

Drug treatment of cerebral ischemia is still controversial after decades of research, and no treatment appears to be firmly established. This is probably not so surprising when even the mechanisms causing the damage are not firmly established. Many good working hypotheses have been considered during the years, however, and it is exciting that recently a scientifically based connection between many of them appears to have evolved. Disturbances in the calcium homeostasis appears to be present in most cases [1,2], and it was therefore natural to start looking at possible protection against ischemic damage with calcium entry blockers a decade ago. In this paper some of the mechanisms whereby calcium theoretically can be involved in ischemic/hypoxic pathophysiology will be briefly discussed.

Keywords

Cerebral Blood Flow Cardiac Arrest Brain Ischemia Neurologic Outcome Mean Arterial Blood Pressure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Cheung JY, Bonventre JV, Malis CD, Leaf A (1986) Calcium and ischemic injury. New Engl J Med 314: 1670–1676PubMedCrossRefGoogle Scholar
  2. 2.
    Siesjö BK (1981) Cell damage in the brain: A speculative synthesis. J Cereb Blood Flow Metab 1: 155–185PubMedCrossRefGoogle Scholar
  3. 3.
    Greer IA (1987) Platelet function and calcium channel-blocking agents. J Clin Pharm Ther 12: 213–222PubMedCrossRefGoogle Scholar
  4. 4.
    McCord JM (1985) Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 312: 159–163PubMedCrossRefGoogle Scholar
  5. 5.
    Rothman SM, Olney JW (1986) Glutamate and the patophysiology of hypoxicischemic brain damage. Ann Neurol 19: 105–111PubMedCrossRefGoogle Scholar
  6. 6.
    Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Chou SN et al. (1983) Cerebral arterial spasm: A controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med, 308: 619–624PubMedCrossRefGoogle Scholar
  7. 7.
    Philippon J, Grot R, Dagreou F, Guggiari M, Rivierez M, Viars P (1986) Prevention of vasospasm in subarachnoid haemorrhage. A controlled study with nimodipine. Acta Neurochir (Wien) 82: 110–114CrossRefGoogle Scholar
  8. 8.
    Petruk KC, West M, Mohr G, Weir BKA, Benoit BG, Gentili F et al. (1988) Nimodipine treatment in poor-grade aneurysm patients. J Neurosurg 68: 505–517PubMedCrossRefGoogle Scholar
  9. 9.
    Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer HJA (1988) A controlled trial of nimodipine in acute ischemic stroke. N Engl J Med 318: 203–207PubMedCrossRefGoogle Scholar
  10. 10.
    Steen PA, Newberg LA, Milde JH, Michenfelder JD (1983) Nimodipine improves cerebral blood flow and neurologic recovery after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 3: 38–43.PubMedCrossRefGoogle Scholar
  11. 11.
    Steen PA, Newberg LA, Milde JH, Michenfelder JD (1984) Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab 4: 82–87PubMedCrossRefGoogle Scholar
  12. 12.
    Newberg LA, Steen PA, Milde JH, Michenfelder JD (1984) Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia. Stroke 15: 666–671PubMedCrossRefGoogle Scholar
  13. 13.
    Stazabe T, Nagai I, Ischikawa T, Takeshita H, Masuda T, Matsumoto M, Tateishi A (1986) Nicardipine increases cerebral blood flow but does not improve neurologic recovery in a canine model of complete cerebral ischemia. J Cereb Blood Flow Metab 6: 684–690CrossRefGoogle Scholar
  14. 14.
    Fleischer JE, Lanier WL, Milde JH, Michenfelder JD (1987) Effect of lidoflazine on cerebral blood flow and neurologic outccme when administered after complete cerebral ischemia in dogs. Anesthesiology, 66: 304–311PubMedCrossRefGoogle Scholar
  15. 15.
    Vaagenes P, Cantadore R, Safar P, Mossy J, Rao G, Diven W, Alexander H, Stezoski W (1984) Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs. Crit Care Med 12: 846–855PubMedCrossRefGoogle Scholar
  16. 16.
    Fleischer JE, Lanier WL, Milde JH, Michenfelder JD (1987) Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates. J Cereb Blood Flow Metab 7: 366–371PubMedCrossRefGoogle Scholar
  17. 17.
    Steen PA, Gisvold SE, Milde JH,. Newberg LA, Scheithaner BW, Lanier WL, Michenfelder JD (1985) Nimodipine improves outcome when given after complete cerebral ischemia in primates. Anesthesiology 62: 406–414PubMedCrossRefGoogle Scholar
  18. 18.
    Smith ML, Kâgström E, Rosen I, Siesjö BK (1983) Effect of the calcium antagonist nimodipine on the delayed hypoperfusion following incomplete ischemia in the rat. J Cereb Blood Flow Metab 3: 543–546PubMedCrossRefGoogle Scholar
  19. 19.
    Forsman M, Aarseth HP, Nordby HK, Skulberg A, Steen PA (1989) Effect of nimodipine on cerebral blood flow and cerebrospinal fluid pressure after cardiac arrest: Correlation with neurologic outcome. Anesth Analg, 68: 436–443PubMedCrossRefGoogle Scholar
  20. 20.
    Roine RO, Kaste M, Kinnunen A, Nikki P (1987) Safety and efficacy of nimodipine in resuscitation of patients outside hospital. Br Med J (Clin Res) 294: 20CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Petter Andreas Steen
    • 1
  1. 1.Department of AnesthesiologyUllevaal University HospitalOslo 4Norway

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