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Dtsch Med Wochenschr 2006; 131(39): 2169-2175
DOI: 10.1055/s-2006-951349
Übersicht | Review article
Kardiologie
© Georg Thieme Verlag KG Stuttgart · New York

Ischämische Prä- und Postkonditionierung

Ischemic pre- and postconditioningG. Heusch1 , R. Schulz1
  • 1Institut für Pathophysiologie, Universitätsklinikum Essen
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Publication History

eingereicht: 17.3.2006

akzeptiert: 7.6.2006

Publication Date:
22 September 2006 (online)

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Zusammenfassung

Ein oder mehrere kurze Zyklen von Ischämie/Reperfusion kurz vor (Präkonditionierung) oder nach (Postkonditionierung) einem längerdauernden Koronarverschluss mit anschließender Reperfusion reduzieren die Infarktgröße. Die protektive Wirkung ist potent, aber auf einen engen zeitlichen Rahmen beschränkt. Im Experiment wurde eine komplexe Signaltransduktionskaskade identifiziert, die letztlich spezifisch den Reperfusionsschaden reduziert. Belege für ischämische Prä- und Postkonditionierung gibt es auch bei Patienten mit koronarer Herzkrankheit.

Summary

One or several short cycles of ischemia/reperfusion before (preconditioning) or after (postconditioning) a sustained coronary occlusion with subsequent reperfusion reduce the ultimate infarct size. The protection is potent, but limited to a narrow time frame. In animal experiments a complex signal transduction cascade was identified which results specifically in a reduction of reperfusion injury. There is evidence for both ischemic pre-and postconditioning in patients with coronary artery disease.

Schlüsselwörter

Myokardinfarkt - Reperfusionsschaden - ischämische Präkonditionierung - ischämische Postkonditionierung

Key words

myocardial infarction - reperfusion injury - ischemic preconditioning - ischemic postconditioning

Literatur

  • 1 Abdallah Y, Gkatzoflia A, Pieper H. et al . Mechanism of cGMP -mediated protection in a cellular model of myocardial reperfusion injury.  Cardiovasc Res. 2005;  66 123-131
    Search in Google Scholar
  • 2 Billinger M, Fleisch M, Eberli F R, Garachemani A, Meier B, Seiler C. Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?.  J Am Coll Cardiol. 1999;  33 1027-1035
    Search in Google Scholar
  • 3 Bolli R. The late phase of preconditioning.  Circ Res. 2000;  87 972-983
    Search in Google Scholar
  • 4 Bolli R, Dawn B, Tang X -L. et al . The nitric oxide hypothesis of late preconditioning.  Basic Res Cardiol. 1998;  93 325-338
    Search in Google Scholar
  • 5 Bopassa J -C, Ferrera R, Gateau-Roesch O, Couture-Lepetit E, Ovize M. PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning.  Cardiovasc Res. 2006;  69 178-185
    Search in Google Scholar
  • 6 Deutsch E, Berger M, Kussmaul W G, Hirshfeld J W, Herrmann H C, Laskey W K. Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features.  Circulation. 1990;  82 2044-2051
    Search in Google Scholar
  • 7 Di Lisa F, Canton M, Menabó R, Dodoni G, Bernardi P. Mitochondria and reperfusion injury. The role of permeability transition.  Basic Res Cardiol. 2003;  98 235-241
    Search in Google Scholar
  • 8 Diaz R J, Armstrong S C, Batthish M, Backx P H, Ganote C E, Wilson G J. Enhanced cell volume regulation: a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes.  J Mol Cell Cardiol. 2003;  35 45-58
    Search in Google Scholar
  • 9 Downey J M, Cohen M V. We think we see a pattern emerging here.  Circulation. 2005;  111 120-121
    Search in Google Scholar
  • 10 Garcia-Dorado D, Rodriguez-Sinovas A, Ruiz-Meana M, Agulló L, Cabestrero A. The end-effectors of preconditioning protection against myocardial cell death secondary to ischemia-reperfusion.  Cardiovasc Res. 2006;  70 274-285
    Search in Google Scholar
  • 11 Hausenloy D J, Mocanu M M, Yellon D M. Cross-talk between the survival kinases during early reperfusion: its contribution to ischemic preconditioning.  Cardiovasc Res. 2004;  63 305-312
    Search in Google Scholar
  • 12 Hausenloy D J, Tsang A, Yellon D M. The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning.  Trends Cardiovasc Med. 2005;  15 69-75
    Search in Google Scholar
  • 13 Heidland U E, Heintzen M P, Michel C J, Strauer B E. Effect of adjunctive intracoronary adenosine on myocardial ischemia, hemodynamic function and left ventricular performance during percutaneous transluminal coronary angioplasty: clinical access to ischemic preconditioning?.  Coron Art Dis. 2000;  11 421-428
    Search in Google Scholar
  • 14 Heinzel F R, Luo Y, Li X. et al . Impairment of diazoxide-induced formation of reactive oxygen species and loss of cardioprotection in connexin 43 deficient mice.  Circ Res. 2005;  97 583-586
    Search in Google Scholar
  • 15 Heusch G. Nitroglycerin and delayed preconditioning in humans: Yet another new mechanism for an old drug?.  Circulation. 2001;  103 2876-2878
    Search in Google Scholar
  • 16 Heusch G. Postconditioning. Old wine in a new bottle?.  J Am Coll Cardiol. 2004a;  44 1111-1112
    Search in Google Scholar
  • 17 Heusch G. Postconditioning. Old wine in a new bottle?.  J Am Coll Cardiol. 2004b;  44 1111-1112
    Search in Google Scholar
  • 18 Heusch G, Cohen M V, Downey J M. Ischemic preconditioning through opening of swelling-activated chloride channels?.  Circ Res. 2001;  89 e48
    Search in Google Scholar
  • 19 Heusch G, Schulz R. Remote Preconditioning.  J Mol Cell Cardiol. 2002;  34 1279-1281
    Search in Google Scholar
  • 20 Inserte J, Garcia-Dorado D, Ruiz-Maena M, Agulló J, Pina P, Soler-Soler J. Ischemic preconditioning attenuates calpain-mediated degradation of structural proteins through a protein kinase A-dependent mechanism.  Cardiovasc Res. 2004;  64 105-114
    Search in Google Scholar
  • 21 Jenkins D P, Pugsley W B, Alkhulaifi A M, Kemp M, Hooper J, Yellon D M. Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery.  Heart. 1997;  77 314-318
    Search in Google Scholar
  • 22 Juhaszova M, Zorov D B, Kim S -H. et al . Glycogen synthase kinase-3ß mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore.  J Clin Invest. 2004;  113 1535-1549
    Search in Google Scholar
  • 23 Kerendi F, Kin H, Halkos M E. et al . Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adeadenosine adenosine receptors.  Basic Res Cardiol. 2005;  100 404-412
    Search in Google Scholar
  • 24 Kin H, Zhao Z -Q, Sun H -Y. et al . Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion.  Cardiovasc Res. 2004;  62 74-85
    Search in Google Scholar
  • 25 Kloner R A, 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
    Search in Google Scholar
  • 26 Laskey W K. Beneficial impact of preconditioning during PTCA on creatine kinase release.  Circulation. 1999;  99 2085-2089
    Search in Google Scholar
  • 27 Leesar M A, Stoddard M, Ahmed M, Broadbent J, Bolli R. Preconditioning in human myocardium with adenosine during coronary angioplasty.  Circulation. 1997;  95 2500-2507
    Search in Google Scholar
  • 28 Leesar M A, Stoddard M F, Dawn B, Jasti V G, Masden R, Bolli R. Delayed preconditioning-mimetic action of nitroglycerin in patients undergoing coronary angioplasty.  Circulation. 2001;  103 2935-2941
    Search in Google Scholar
  • 29 Leesar M A, Stoddard M F, Manchikalapudi S, Bolli R. Bradykinin-induced preconditioning in patients undergoing coronary angioplasty.  J Am Coll Cardiol. 1999;  34 639-650
    Search in Google Scholar
  • 30 Li X, Heinzel F R, Boengler K, Schulz R, Heusch G. Role of connexin 43 in ischemic preconditioning does not involve intercellular communications through gap junctions.  J Mol Cell Cardiol. 2004;  36 161-163
    Search in Google Scholar
  • 31 Marber M S, Latchman D S, Walker J M, Yellon D M. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.  Circulation. 1993;  88 1264-1272
    Search in Google Scholar
  • 32 Meier J J, Gallwitz B, Schmidt W E, Mügge A, Nauck M A. Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important ?.  Heart. 2004;  90 9-12
    Search in Google Scholar
  • 33 Murry C E, Jennings R B, Reimer K A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.  Circulation. 1986;  74 1124-1136
    Search in Google Scholar
  • 34 Nakagawa Y, Ito H, Kitakaze M. et al . Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of „preconditioning”.  J Am Coll Cardiol. 1995;  25 1076-1083
    Search in Google Scholar
  • 35 Ottani F, Galvani M, Ferrini D. et al . Prodromal angina limits infarct size. A role for ischemic preconditioning.  Circulation. 1995;  91 291-297
    Search in Google Scholar
  • 36 Pain T, Yang X -M, Critz S D. et al . Opening of mitochondrial KATP channels triggers the preconditioned state by generating free radicals.  Circ Res. 2000;  87 460-466
    Search in Google Scholar
  • 37 Penna C, Rastaldo R, Mancardi D. et al . Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K+ channel and protein kinase C activation.  Basic Res Cardiol. 2006;  101 180-189
    Search in Google Scholar
  • 38 Piper H M, Meuter K, Schäfer C. Cellular mechanisms of ischemia-reperfusion injury.  Ann Thorac Surg. 2003;  75 S644-S648
    Search in Google Scholar
  • 39 Reimer K A, Jennings R B, Cobb F R. et al . Animal models for protecting ischemic myocardium: results of the NHLBI cooperative study. Comparison of unconscious and conscious dog models.  Circ Res. 1985;  56 651-665
    Search in Google Scholar
  • 40 Schaper W, Görge G, Winkler B, Schaper J. The collateral circulation of the heart.  Prog Cardiovasc Dis. 1988;  31 57-77
    Search in Google Scholar
  • 41 Schulz R, Cohen M V, Behrends M, Downey J M, Heusch G. Signal transduction of ischemic preconditioning.  Cardiovasc Res. 2001;  52 181-198
    Search in Google Scholar
  • 42 Schulz R, Gres P, Skyschally A. et al . Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo.  Faseb J. 2003;  17 1355-1357
    Search in Google Scholar
  • 43 Staat P, Rioufol G, Piot C. et al . Postconditioning the human heart.  Circulation. 2005;  112 2143-2148
    Search in Google Scholar
  • 44 Tomai F, Crea F, Gaspardone A. et al . Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker.  Circulation. 1994;  90 700-705
    Search in Google Scholar
  • 45 Tomai F, Crea F, Gaspardone A. et al . Effects of naloxone on myocardial ischemic preconditioning in humans.  J Am Coll Cardiol. 1999;  33 1863-1869
    Search in Google Scholar
  • 46 Tsang A, Hausenloy D J, Yellon D M. Myocardial postconditioning: reperfusion injury revisited.  Am J Physiol Heart Circ Physiol. 2005;  289 H2-H7
    Search in Google Scholar
  • 47 Valen G, Vaage J. Pre- and postconditioning during cardiac surgery.  Basic Res Cardiol. 2005;  100 179-186
    Search in Google Scholar
  • 48 Vinten-Johansen J, Yellon D M, Opie L H. Postconditioning. A simple, clinically applicable procedure to improve revascularization in acute myocardial infarction.  Circulation. 2005;  112 2085-2088
    Search in Google Scholar
  • 49 Vinten-Johansen J, Zhao Z -Q, Zatta A J, Kin H, Halkos M E, Kerendi F. Postconditioning. A new link in nature’s armor against myocardial ischemia-reperfusion injury.  Basic Res Cardiol. 2005;  295 295-310
    Search in Google Scholar
  • 50 Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation.  J Exp Med. 1999;  189 1699-1706
    Search in Google Scholar
  • 51 Yang X -M, Philipp S, Downey J M, Cohen M V. Postconditioning’s protection is not dependent on circulating blood factors or cells but involves adenosine receptors and requires PI3-kinase and guanylyl cyclase activation.  Basic Res Cardiol. 2005;  100 57-63
    Search in Google Scholar
  • 52 Yang X -M, Proctor J B, Cui L, Krieg T, Downey J M, Cohen M V. Multiple, brief coronary occlusions during early reperfusion protect hearts by targeting cell signaling pathways.  J Am Coll Cardiol. 2004;  44 1103-1110
    Search in Google Scholar
  • 53 Yellon D M, Alkhulaifi A M, Pugsley W B. Preconditioning the human myocardium.  Lancet. 1993;  342 276-277
    Search in Google Scholar
  • 54 Yellon D M, Downey J M. Preconditioning the myocardium: From cellular physiology to clinical cardiology.  Physiol Rev. 2003;  83 1113-1151
    Search in Google Scholar
  • 55 Zhao Z -Q, Corvera J S, Halkos M E. et al . Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning.  Am J Physiol Heart Circ Physiol. 2003;  285 H579-H588
    Search in Google Scholar

Prof. Dr. med. Dr. h. c. Gerd Heusch

Direktor des Instituts für Pathophysiologie, Zentrum für Innere Medizin, Universitätsklinikum Essen

Hufelandstraße 55

45122 Essen

Email: gerd.heusch@uni-essen.de