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Clinical Pharmacology of Preconditioning and Adenosinergic Drugs

  • Herman Van Belle
Chapter
  • 43 Downloads
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 194)

Abstract

On an array of cells and organs adenosine may exert a multitude of effects, all apparently serving one purpose: restore and maintain the balance between energy supply and demand (for recent reviews, Refs. 1,2). Its rapid formation in response to ischemia constitutes a natural defense system which appears to be extremely efficient, hence very attractive, for three reasons:
  1. 1.

    Adenosine’s formation is the simple consequence of a disequilibrium between dephosphorylation of ATP (’energy demand) and rephosphorylation (mitochondrial oxidative metabolism > energy supply). AMP, adenosine’s immediate precursor, is a most sensitive sensor of energy shortage.

     
  2. 2.

    Adenosine’s formation is small and temporarily. It is limited to the ischemic area within most vital organs and only when oxygen supply is insufficient to cope with the demand. Nature has even taken precautions to prevent spreading of this potent messenger to normoxic regions or organs by providing rapid catabolism in the endothelial cells lining the microvessels, and in erythrocytes.

     
  3. 3.

    Adenosine’s production initiates a cascade of effects. Its most prominent activity, microvascular vasodilatation, will be a first-aid measure to restore the balance. If not sufficient, more adenosine will accumulate and more receptors within reach may be triggered: demand will be moderated and there will be a delay in the start of a vicious circle of events leading to major organ damage.

     

Keywords

Adenosine Deaminase Nucleoside Transport Left Ventricular Ejection Time Mitochondrial Oxidative Metabolism European Stroke Prevention Study 
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.
    Van Belle H. Specific metabolically active anti-ischemic agents: adenosine and nucleoside transport inhibitors. In Singh BN, Dzau VJ, Vanhoutte PM et al, eds. Cardiovascular Pharmacology and Therapeutics; Churchill Livingstone, 1993:217–235.Google Scholar
  2. 2.
    Van Belle H: Adenosine promotors: An overview of existing strategies. Curr Opin Invest Drugs 1993;2:1191–1199.Google Scholar
  3. 3.
    Kloner RA, Shook T, Przyklenk K. et al. Previous angina alters in-hospital outcome in TIMI-4. A clinical correlate to preconditioning ? Circulation 1995;91:37–47.PubMedCrossRefGoogle Scholar
  4. 4.
    Miura T, Iimura O. Infarct size limitation by preconditioning: its phenomenological features and the key role of adenosine. Cardiovasc Res 1993;27:36–42.PubMedCrossRefGoogle Scholar
  5. 5.
    Kollias-Baker C, Ruble J, Dennis D et al. Allosteric enhancer PD81723 acts by novel mechanism to potentiate cardiac actions of adenosine. Circ.Res. 1994;75:961–971.PubMedCrossRefGoogle Scholar
  6. 6.
    Rousseau MF, Van Eyll C, Hayashida W et al. Intravenous dipyridamole infusion during thrombolysis improves the recovery of left ventricular function. Circulation 1995;88: Abstr. 0841.Google Scholar
  7. 7.
    Strauer BE, Heidland HE, Heintzen MP et al. Pharmakologische Myokardprotektion während perkutaner transluminaler Koronarangioplastie (PTCA) durch Dipyridamole intrakoronär: Hamodynamische, Kontraktile und Ventrikeldynamische Konsequenzen. Z.Kardiol. 1995;84: 898–910.PubMedGoogle Scholar
  8. 8.
    Ferguson JJ. Research News: Second European Stroke Prevention Study. Circulation 1996;93: 399.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

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  • Herman Van Belle

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