© 2000 American Heart Association, Inc.
Review |
The Preconditioning Phenomenon
A Tool for the Scientist or a Clinical Reality?
From The Hatter Institute, Department of Academic and Clinical Cardiology, University College London Hospitals and Medical School, London, UK.
Correspondence to D.M. Yellon, The Hatter Institute, Department of Academic and Clinical Cardiology, University College Hospital, Grafton Way, London WC1E 6DB, UK. E-mail s.bush-cavell{at}ucl.ac.uk
Abstract—The possibility that an innate mechanism of myocardial protection might be inducible in the human heart has generated considerable excitement and enthusiastic research. The potential to enhance myocardial resistance to ischemic injury in patients suffering the consequences of coronary artery disease has led to studies with more direct clinical relevance. However, in common with many other areas of clinical interest based on advances in basic scientific understanding, early enthusiasm may be disproportionate to ultimate therapeutic significance. There can be little doubt that our understanding of the mechanisms underlying the pathogenesis of ischemia-reperfusion injury has been enhanced significantly by the plethora of research stimulated by interest in endogenous myocardial protection. Direct extrapolation of observations in the laboratory to the cardiology clinic or operating theater is tempting but should be avoided. The results of recent clinical experiments that suggest that preconditioning can protect against ischemia, although encouraging, should be interpreted cautiously, with particular attention to the limitations of the end points available. A reasoned evaluation of recent research should prevent unrealistic expectations and allow improved design of future trials so that this potent adaptive phenomenon can be exploited to its maximum potential.
Key Words: preconditioning • unstable angina • myocardial infarction • coronary angioplasty • coronary bypass surgery
This article has been cited by other articles:
 |
|
 |
|
  M. L. Hart, C. Much, D. Kohler, J. Schittenhelm, I. C. Gorzolla, G. L. Stahl, and H. K. Eltzschig Use of a hanging-weight system for liver ischemic preconditioning in mice Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1431 - G1440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Mentzer Jr, M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2008; 3(2008): 443 - 464. [Full Text]
|
|
|
|
 |
|
 I. Khaliulin, S. J. Clarke, H. Lin, J. Parker, M.-S. Suleiman, and A. P. Halestrap Temperature preconditioning of isolated rat hearts - a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore J. Physiol., June 15, 2007; 581(3): 1147 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Burdess and D Newby Harnessing the preconditioning phenomenon: does remote organ ischaemia provide the answer? Heart, October 1, 2006; 92(10): 1367 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Inserte, D. Garcia-Dorado, V. Hernando, I. Barba, and J. Soler-Soler Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion Cardiovasc Res, May 1, 2006; 70(2): 364 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Turnbull, H.-Z. Zhou, P. M. Swigart, S. Turcato, J. S. Karliner, B. R. Conklin, P. C. Simpson, and A. J. Baker Sustained preconditioning induced by cardiac transgenesis with the tetracycline transactivator Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1103 - H1109. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bolli and A. Abdel-Latif No Pain, No Gain: The Useful Function of Angina Circulation, December 6, 2005; 112(23): 3541 - 3543. [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Canyon and G. P. Dobson Pretreatment with an adenosine A1 receptor agonist and lidocaine: A possible alternative to myocardial ischemic preconditioning J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 371 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okada, H. Otani, Y. Wu, T. Uchiyama, S. Kyoi, R. Hattori, T. Sumida, H. Fujiwara, and H. Imamura Integrated pharmacological preconditioning and memory of cardioprotection: role of protein kinase C and phosphatidylinositol 3-kinase Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H761 - H767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barandon, P. Dufourcq, P. Costet, C. Moreau, C. Allieres, D. Daret, P. D. Santos, J.-M. D. Lamaziere, T. Couffinhal, and C. Duplaa Involvement of FrzA/sFRP-1 and the Wnt/Frizzled Pathway in Ischemic Preconditioning Circ. Res., June 24, 2005; 96(12): 1299 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-Q. Jin, E. J. Goetzl, and J. S. Karliner Sphingosine Kinase Activation Mediates Ischemic Preconditioning in Murine Heart Circulation, October 5, 2004; 110(14): 1980 - 1989. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mayr, B. Metzler, Y.-L. Chung, E. McGregor, U. Mayr, H. Troy, Y. Hu, M. Leitges, O. Pachinger, J. R. Griffiths, et al. Ischemic preconditioning exaggerates cardiac damage in PKC-{delta} null mice Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H946 - H956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, E. Kodani, J. Wang, S. X. Zhang, H. Takano, X.-L. Tang, and R. Bolli Cardioprotection During the Final Stage of the Late Phase of Ischemic Preconditioning Is Mediated by Neuronal NO Synthase in Concert With Cyclooxygenase-2 Circ. Res., July 9, 2004; 95(1): 84 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T B Lindhardt, N Gadsboll, H Kelbaek, K Saunamaki, J K Madsen, P Clemmensen, B Hesse, and S Haunso Pharmacological modulation of the ATP sensitive potassium channels during repeated coronary occlusions: no effect on myocardial ischaemia or function Heart, April 1, 2004; 90(4): 425 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Baker Ischemic preconditioning in the brain/Preconditionnement ischemique cerebral Can J Anesth, March 1, 2004; 51(3): 201 - 205. [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Leesar, M. F. Stoddard, Y.-T. Xuan, X.-L. Tang, and R. Bolli Nonelectrocardiographic evidence that both ischemic preconditioning and adenosine preconditioning exist in humans J. Am. Coll. Cardiol., August 6, 2003; 42(3): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Cai, D. J. Manalo, G. Wei, E. R. Rodriguez, K. Fox-Talbot, H. Lu, J. L. Zweier, and G. L. Semenza Hearts From Rodents Exposed to Intermittent Hypoxia or Erythropoietin Are Protected Against Ischemia-Reperfusion Injury Circulation, July 8, 2003; 108(1): 79 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Bartling, I. Friedrich, R.-E. Silber, and A. Simm Ischemic preconditioning is not cardioprotective in senescent human myocardium Ann. Thorac. Surg., July 1, 2003; 76(1): 105 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. o. Cosar and C. J. O'Connor Hibernation, Stunning, and Preconditioning: Historical Perspective, Current Concepts, Clinical Applications, and Future Implications Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2003; 7(2): 115 - 140. [Abstract] [PDF]
|
|
|
|
|
|
E J P Lamfers, T E H Hooghoudt, D P Hertzberger, A Schut, P W J Stolwijk, and F W A Verheugt Abortion of acute ST segment elevation myocardial infarction after reperfusion: incidence, patients' characteristics, and prognosis Heart, May 1, 2003; 89(5): 496 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, Y. Guo, Y.-T. Xuan, C. J. Lowenstein, S. C. Stevenson, S. D. Prabhu, W.-J. Wu, Y. Zhu, and R. Bolli Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2-Dependent Mechanism Circ. Res., April 18, 2003; 92(7): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, E. Kodani, Y. u-T. Xuan, B. Dawn, X.-L. Tang, and R. Bolli Effect of aspirin on late preconditioning against myocardial stunning in conscious rabbits J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1183 - 1194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Przyklenk and G. Heusch Late preconditioning against myocardial stunning: Does aspirin close the "second window" of endogenous cardioprotection? J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1195 - 1197. [Full Text] [PDF]
|
|
|
|
|
|
J. Vaage and G. Valen Preconditioning and cardiac surgery Ann. Thorac. Surg., February 1, 2003; 75(2): S709 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Skyschally, R. Schulz, P. Gres, H.-G. Korth, and G. Heusch Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H698 - H703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Mentzer Jr., M. S. Jahania, and R. D. Lasley Myocardial Protection Card. Surg. Adult, January 1, 2003; 2(2003): 413 - 438. [Full Text]
|
|
|
|
|
|
P. Taggart and D. M. Yellon Preconditioning and Arrhythmias Circulation, December 10, 2002; 106(24): 2999 - 3001. [Full Text] [PDF]
|
|
|
|
|
|
K. Suzuki, B. Murtuza, I. A. Sammut, N. Latif, J. Jayakumar, R. T. Smolenski, Y. Kaneda, Y. Sawa, H. Matsuda, and M. H. Yacoub Heat Shock Protein 72 Enhances Manganese Superoxide Dismutase Activity During Myocardial Ischemia-Reperfusion Injury, Associated With Mitochondrial Protection and Apoptosis Reduction Circulation, September 24, 2002; 106(12_suppl_1): I-270 - I-276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Bolli, K. Shinmura, X.-L. Tang, E. Kodani, Y.-T. Xuan, Y. Guo, and B. Dawn Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning Cardiovasc Res, August 15, 2002; 55(3): 506 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Strohm, M. Barancik, M.-L. von Bruehl, M. Strniskova, C. Ullmann, R. Zimmermann, and W. Schaper Transcription inhibitor actinomycin-D abolishes the cardioprotective effect of ischemic reconditioning Cardiovasc Res, August 15, 2002; 55(3): 602 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Z. Zhou, J. S. Karliner, and M. O. Gray Moderate alcohol consumption induces sustained cardiac protection by activating PKC-epsilon and Akt Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H165 - H174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Giblin, Y. Cui, L. H. Clapp, and A. Tinker Assembly Limits the Pharmacological Complexity of ATP-sensitive Potassium Channels J. Biol. Chem., April 12, 2002; 277(16): 13717 - 13723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Hampson and M. Grimaldi 12-Hydroxyeicosatetrenoate (12-HETE) Attenuates AMPA Receptor-Mediated Neurotoxicity: Evidence for a G-Protein-Coupled HETE Receptor J. Neurosci., January 1, 2002; 22(1): 257 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Vakili, R. C. Kaplan, and D. L. Brown Sex-Based Differences in Early Mortality of Patients Undergoing Primary Angioplasty for First Acute Myocardial Infarction Circulation, December 18, 2001; 104(25): 3034 - 3038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Kloner and R. B. Jennings Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications: Part 2 Circulation, December 18, 2001; 104(25): 3158 - 3167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch Nitroglycerin and Delayed Preconditioning in Humans : Yet Another New Mechanism for an Old Drug? Circulation, June 19, 2001; 103(24): 2876 - 2878. [Full Text] [PDF]
|
|
|
|
|
|
M. A. Leesar, M. F. Stoddard, B. Dawn, V. G. Jasti, R. Masden, and R. Bolli Delayed Preconditioning-Mimetic Action of Nitroglycerin in Patients Undergoing Coronary Angioplasty Circulation, June 19, 2001; 103(24): 2935 - 2941. [Abstract] [Full Text] [PDF]
|
|