Drugs & Aging

, Volume 28, Issue 5, pp 331–343 | Cite as

Efficacy of Cardioprotective ‘Conditioning’ Strategies in Aging and Diabetic Cohorts

The Co-Morbidity Conundrum
Current Opinion

Abstract

Evidence obtained in multiple experimental models has revealed that cardiac ‘conditioning’ strategies — including ischaemic preconditioning, postconditioning, remote conditioning and administration of pharmacological conditioning mimetics — are profoundly protective and significantly attenuate myocardial ischaemia-reperfusion injury. As a result, there is considerable interest in translating these cardioprotective paradigms from the laboratory to patients. However, the majority of studies investigating conditioning-induced cardioprotection have utilized healthy adult animals devoid of the risk factors and co-morbidities associated with cardiovascular disease and acute myocardial infarction. The aim of this article is to summarize the growing consensus that two well established risk factors, aging and diabetes mellitus, may render the heart refractory to the favourable effects of myocardial conditioning, and discuss the clinical implications of a loss in efficacy of cardiac conditioning paradigms in these patient populations.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this article. The author has no conflicts of interest that are directly relevant to the content of this article. The author gratefully acknowledges Peter Whittaker, PhD, for critical discussions during the preparation of this article.

References

  1. 1.
    American Heart Association-International Cardiovascular Disease Statistics. 2009 update [online]. Available from URL: http://americanheart.org/downloadable/heart/1236204012112INTL.pdf [Accessed 2010 Oct 12]
  2. 2.
    Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics: 2010 update — a report from the American Heart Association. Circulation 2010; 121: e46–215PubMedCrossRefGoogle Scholar
  3. 3.
    Bolli R, Becker L, Gross G, et al. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ Res 2004; 95: 125–34PubMedCrossRefGoogle Scholar
  4. 4.
    Hausenloy DJ, Baxter G, Bell R, et al. Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations. Basic Res Cardiol 2010; 677–86Google Scholar
  5. 5.
    Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest 1985; 76: 1713–9PubMedCrossRefGoogle Scholar
  6. 6.
    Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007; 357: 1121–35PubMedCrossRefGoogle Scholar
  7. 7.
    Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 1124–36PubMedCrossRefGoogle Scholar
  8. 8.
    Zhao ZQ, Corvera JS, Halkos ME, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol 2003; 285: H579–88Google Scholar
  9. 9.
    Przyklenk K, Bauer B, Ovize M, et al. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 1993; 87: 893–9PubMedCrossRefGoogle Scholar
  10. 10.
    Granfeldt A, Lefer DJ, Vinten-Johansen J. Protective ischaemia in patients: preconditioning and postconditioning. Cardiovasc Res 2009; 83: 234–46PubMedCrossRefGoogle Scholar
  11. 11.
    Hausenloy DJ, Yellon DM. Preconditioning and post-conditioning: underlying mechanisms and clinical application. Atherosclerosis 2009; 204: 334–41PubMedCrossRefGoogle Scholar
  12. 12.
    Ludman AJ, Yellon DM, Hausenloy DJ. Cardiac preconditioning for ischaemia: lost in translation. Dis Model Mech 2010; 3: 35–8PubMedCrossRefGoogle Scholar
  13. 13.
    Peart JN, Headrick JP. Clinical cardioprotection and the value of conditioning responses. Am J Physiol Heart Circ Physiol 2009; 296: H1705–20PubMedCrossRefGoogle Scholar
  14. 14.
    Mewton N, Ivanes F, Cour M, et al. Postconditioning: from experimental proof to clinical concept. Dis Model Mech 2010; 3: 39–44PubMedCrossRefGoogle Scholar
  15. 15.
    Hausenloy DJ, Mwamure PK, Venugopal V, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 2007; 370: 575–9PubMedCrossRefGoogle Scholar
  16. 16.
    Thielmann M, Kottenberg E, Boengler K, et al. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol 2010; 105: 657–64PubMedCrossRefGoogle Scholar
  17. 17.
    Botker HE, Kharbanda R, Schmidt MR, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet 2010; 375: 727–34PubMedCrossRefGoogle Scholar
  18. 18.
    Przyklenk K, Kloner RA. Ischemic preconditioning: exploring the paradox. Prog Cardiovasc Dis 1998; 40: 517–47PubMedCrossRefGoogle Scholar
  19. 19.
    Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 2003; 83: 1113–51PubMedGoogle Scholar
  20. 20.
    Cohen MV, Downey JM. Ischemic postconditioning: from receptor to end-effector. Antioxid Redox Signal 2011; 14: 821–31PubMedCrossRefGoogle Scholar
  21. 21.
    Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway. Cardiovasc Res 2004; 61: 448–60PubMedCrossRefGoogle Scholar
  22. 22.
    Przyklenk K, Maynard M, Whittaker P. First molecular evidence that inositol trisphosphate signaling contributes to infarct size reduction with preconditioning. Am J Physiol 2006; 291: H2008–12Google Scholar
  23. 23.
    Cohen MV, Downey JM. Adenosine: trigger and mediator of cardioprotection. Basic Res Cardiol 2008; 103: 203–15PubMedCrossRefGoogle Scholar
  24. 24.
    Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev 2008; 88: 581–609PubMedCrossRefGoogle Scholar
  25. 25.
    Yang X, Cohen MV, Downey JM. Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 2010; 24: 225–34PubMedCrossRefGoogle Scholar
  26. 26.
    Nishihara M, Miura T, Miki T, et al. Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection. J Mol Cell Cardiol 2007; 43: 564–70PubMedCrossRefGoogle Scholar
  27. 27.
    Terashima Y, Sato T, Yano T, et al. Roles of phospho-GSK-3beta in myocardial protection afforded by activation of the mitochondrial K ATP channel. J Mol Cell Cardiol 2010; 49: 762–70PubMedCrossRefGoogle Scholar
  28. 28.
    Juhaszova M, Zorov DB, Yaniv Y, et al. Role of glycogen synthase kinase-3beta in cardioprotection. Circ Res 2009; 104: 1240–52PubMedCrossRefGoogle Scholar
  29. 29.
    Miura T, Tanno M, Sato T. Mitochondrial kinase signalling pathways in myocardial protection from ischaemia/reperfusion-induced necrosis. Cardiovasc Res 2010; 88:7–15PubMedCrossRefGoogle Scholar
  30. 30.
    Murphy E, Steenbergen C. What makes the mitochondria a killer? Can we condition them to be less destructive? Biochim Biophys Acta. Epub 2010 Sept 15Google Scholar
  31. 31.
    Halestrap AP, Clarke SJ, Khaliulin I. The role of mitochondria in protection of the heart by preconditioning. Biochim Biophys Acta 2007; 1767: 1007–31PubMedCrossRefGoogle Scholar
  32. 32.
    Javadov SA, Clarke S, Das M, et al. Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart. J Physiol 2003; 549: 513–24PubMedCrossRefGoogle Scholar
  33. 33.
    Vinten-Johansen J, Zhao ZQ, Zatta AJ, et al. Postconditioning: a new link in nature’s armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol 2005; 100: 295–310PubMedCrossRefGoogle Scholar
  34. 34.
    Vinten-Johansen J, Granfeldt A, Mykytenko J, et al. The multi-dimensional physiological responses to post-conditioning. Antioxid Redox Signal 2011; 14: 791–810PubMedCrossRefGoogle Scholar
  35. 35.
    Skyschally A, van Caster P, Boengler K, et al. Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res 2009; 104: 15–8PubMedCrossRefGoogle Scholar
  36. 36.
    Lacerda L, Somers S, Opie LH, et al. Ischaemic post-conditioning protects against reperfusion injury via the SAFE pathway. Cardiovasc Res 2009; 84: 201–8PubMedCrossRefGoogle Scholar
  37. 37.
    Lecour S. Activation of the protective Survivor Activating Factor Enhancement (SAFE) pathway against reperfusion injury: does it go beyond the RISK pathway? J Mol Cell Cardiol 2009; 47: 32–40PubMedCrossRefGoogle Scholar
  38. 38.
    Whittaker P, Przyklenk K. Reduction of infarct size in vivo with ischemic preconditioning: mathematical evidence for protection via non-ischemic tissue. Basic Res Cardiol 1994; 89: 6–15PubMedCrossRefGoogle Scholar
  39. 39.
    Przyklenk K, Darling CE, Dickson EW, et al. Cardioprotection ‘outside the box’: the evolving paradigm of remote preconditioning. Basic Res Cardiol 2003; 98: 149–57PubMedGoogle Scholar
  40. 40.
    Gho BC, Schoemaker RG, van den Doel MA, et al. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 1996; 94: 2193–200PubMedCrossRefGoogle Scholar
  41. 41.
    Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 1997; 96: 1641–6PubMedCrossRefGoogle Scholar
  42. 42.
    Schmidt MR, Smerup M, Konstantinov IE, et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol 2007; 292: H1883–90PubMedCrossRefGoogle Scholar
  43. 43.
    Kerendi F, Kin H, Halkos ME, et al. Remote post-conditioning: brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol 2005; 100: 404–12PubMedCrossRefGoogle Scholar
  44. 44.
    Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res 2008; 79: 377–86PubMedCrossRefGoogle Scholar
  45. 45.
    Kharbanda RK, Nielsen TT, Redington AN. Translation of remote ischaemic preconditioning into clinical practice. Lancet 2009; 374: 1557–65PubMedCrossRefGoogle Scholar
  46. 46.
    Shimizu M, Tropak M, Diaz RJ, et al. Transient limb ischaemia remotely preconditions through a humoral mechanism acting directly on the myocardium: evidence suggesting cross-species protection. Clin Sci (Lond) 2009; 117: 191–200CrossRefGoogle Scholar
  47. 47.
    Li J, Xuan W, Yan R, et al. Remote preconditioning provides potent cardioprotection via PI3k/Akt activation and is associated with nuclear accumulation of beta-catenin. Clin Sci (Lond) 2011; 120: 451–62CrossRefGoogle Scholar
  48. 48.
    Weber C. Far from the heart: receptor cross-talk in remote conditioning. Nat Med 2010; 16: 760–2PubMedCrossRefGoogle Scholar
  49. 49.
    Lim SY, Yellon DM, Hausenloy DJ. The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res Cardiol 2010; 105: 651–5PubMedCrossRefGoogle Scholar
  50. 50.
    Burley DS, Baxter GF. Pharmacological targets revealed by myocardial postconditioning. Curr Opin Pharmacol 2009; 9: 177–88PubMedCrossRefGoogle Scholar
  51. 51.
    Peart JN, Gross GJ. Adenosine and opioid receptor-mediated cardioprotection in the rat: evidence for cross-talk between receptors. Am J Physiol Heart Circ Physiol 2003; 285: H81–9PubMedGoogle Scholar
  52. 52.
    Peart JN, Gross GJ. Cross-talk between adenosine and opioid receptors. Drug News Perspect 2005; 18: 237–42PubMedCrossRefGoogle Scholar
  53. 53.
    Peart JN, Gross GJ. Exogenous activation of delta- and kappa-opioid receptors affords cardioprotection in isolated murine heart. Basic Res Cardiol 2004; 99: 29–37PubMedCrossRefGoogle Scholar
  54. 54.
    Peart JN, Gross ER, Gross GJ. Opioid-induced preconditioning: recent advances and future perspectives. Vascul Pharmacol 2005; 42: 211–8PubMedCrossRefGoogle Scholar
  55. 55.
    Zaugg M, Lucchinetti E, Uecker M, et al. Anaesthetics and cardiac preconditioning, part I: signalling and cytoprotective mechanisms. Br J Anaesth 2003; 91: 551–65PubMedCrossRefGoogle Scholar
  56. 56.
    Zaugg M, Lucchinetti E, Garcia C, et al. Anaesthetics and cardiac preconditioning, part II: clinical implications. Br J Anaesth 2003; 91: 566–76PubMedCrossRefGoogle Scholar
  57. 57.
    Tanaka K, Ludwig LM, Kersten JR, et al. Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology 2004; 100: 707–21PubMedCrossRefGoogle Scholar
  58. 58.
    Riess ML, Stowe DF, Warltier DC. Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside? Am J Physiol Heart Circ Physiol 2004; 286: H1603–7PubMedCrossRefGoogle Scholar
  59. 59.
    Gomez L, Thibault H, Gharib A, et al. Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice. Am J Physiol Heart Circ Physiol 2007; 293: H1654–61PubMedCrossRefGoogle Scholar
  60. 60.
    Lim SY, Davidson SM, Hausenloy DJ, et al. Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res 2007; 75: 530–5PubMedCrossRefGoogle Scholar
  61. 61.
    Hausenloy DJ, Ong SB, Yellon DM. The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol 2009; 104: 189–202PubMedCrossRefGoogle Scholar
  62. 62.
    Gomez L, Li B, Mewton N, et al. Inhibition of mitochondrial permeability transition pore opening: translation to patients. Cardiovasc Res 2009; 83: 226–33PubMedCrossRefGoogle Scholar
  63. 63.
    Ferdinandy P, Schulz R, Baxter GF. Interaction of cardiovascular risk factors with myocardial ischemia/reperfusion injury, preconditioning, and post-conditioning. Pharmacol Rev 2007; 59: 418–58PubMedCrossRefGoogle Scholar
  64. 64.
    Miki T, Miura T, Tsuchida A, et al. Cardioprotective mechanism of ischemic preconditioning is impaired by post-infarct ventricular remodeling through angiotensin II type 1 receptor activation. Circulation 2000; 102: 458–63PubMedCrossRefGoogle Scholar
  65. 65.
    Miki T, Miura T, Tanno M, et al. Interruption of signal transduction between G protein and PKC-epsilon underlies the impaired myocardial response to ischemic preconditioning in postinfarct remodeled hearts. Mol Cell Biochem 2003; 247: 185–93PubMedCrossRefGoogle Scholar
  66. 66.
    Song X, Li G, Vaage J, et al. Effects of sex, gonadectomy, and oestrogen substitution on ischaemic preconditioning and ischaemia-reperfusion injury in mice. Acta Physiol Scand 2003; 177: 459–66PubMedCrossRefGoogle Scholar
  67. 67.
    Murphy E, Steenbergen C. Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury. Cardiovasc Res 2007; 75: 478–86PubMedCrossRefGoogle Scholar
  68. 68.
    Lagranha CJ, Deschamps A, Aponte A, et al. Sex differences in the phosphorylation of mitochondrial proteins result in reduced production of reactive oxygen species and cardioprotection in females. Circ Res 2010; 106: 1681–91PubMedCrossRefGoogle Scholar
  69. 69.
    World Health Organization. Health topics [online]. Available from URL: http://www.who.int/topics/ageing/en/ [Accessed 2010 Oct 15]
  70. 70.
    McKay CR, Rich MW, Vlietstra RE, et al. Executive summary: pivotal research in cardiovascular syndromes in the elderly. Am J Geriatr Cardiol 2000; 9: 243–50PubMedCrossRefGoogle Scholar
  71. 71.
    Swynghedauw B, Besse S, Assayag P, et al. Molecular and cellular biology of the senescent hypertrophied and failing heart. Am J Cardiol 1995; 76: 2D–7DPubMedCrossRefGoogle Scholar
  72. 72.
    Roka F, Freissmuth M, Nanoff C. G protein-dependent signalling and ageing. Exp Gerontol 2000; 35: 133–43PubMedCrossRefGoogle Scholar
  73. 73.
    Korzick DH, Holiman DA, Boluyt MO, et al. Diminished alpha1-adrenergic-mediated contraction and translocation of PKC in senescent rat heart. Am J Physiol Heart Circ Physiol 2001; 281: H581–9PubMedGoogle Scholar
  74. 74.
    Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part I: aging arteries — a ‘set up’ for vascular disease. Circulation 2003; 107: 139–46PubMedCrossRefGoogle Scholar
  75. 75.
    Naito Z, Takashi E, Xu G, et al. Different influences of hyperglycemic duration on phosphorylated extracellular signal-regulated kinase 1/2 in rat heart. Exp Mol Pathol 2003; 74: 23–32PubMedCrossRefGoogle Scholar
  76. 76.
    Taylor RP, Starnes JW. Age, cell signalling and cardioprotection. Acta Physiol Scand 2003; 178: 107–16PubMedCrossRefGoogle Scholar
  77. 77.
    Hunter JC, Korzick DH. Age- and sex-dependent alterations in protein kinase C (PKC) and extracellular regulated kinase 1/2 (ERK1/2) in rat myocardium. Mech Ageing Dev 2005; 126: 535–50PubMedCrossRefGoogle Scholar
  78. 78.
    Juhaszova M, Rabuel C, Zorov DB, et al. Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res 2005; 66: 233–44PubMedCrossRefGoogle Scholar
  79. 79.
    Gross ER, Hsu AK, Gross GJ. Diabetes abolishes morphine-induced cardioprotection via multiple pathways upstream of glycogen synthase kinase-3beta. Diabetes 2007; 56: 127–36PubMedCrossRefGoogle Scholar
  80. 80.
    Ekladous D, Mehdi MZ, Costa M, et al. Tissue- and fibre-specific modifications of insulin-signalling molecules in cardiac and skeletal muscle of diabetic rats. Clin Exp Pharmacol Physiol 2008; 35: 971–8PubMedCrossRefGoogle Scholar
  81. 81.
    Boengler K, Schulz R, Heusch G. Loss of cardioprotection with ageing. Cardiovasc Res 2009; 83: 247–61PubMedCrossRefGoogle Scholar
  82. 82.
    Sivitz WI, Yorek MA. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid Redox Signal 2010; 12: 537–77PubMedCrossRefGoogle Scholar
  83. 83.
    Long P, Nguyen Q, Thurow C, et al. Caloric restriction restores the cardioprotective effect of preconditioning in the rat heart. Mech Ageing Dev 2002; 123: 1411–3PubMedCrossRefGoogle Scholar
  84. 84.
    Schulman D, Latchman DS, Yellon DM. Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2001; 281: H1630–6PubMedGoogle Scholar
  85. 85.
    Abete P, Calabrese C, Ferrara N, et al. Exercise training restores ischemic preconditioning in the aging heart. J Am Coll Cardiol 2000; 36: 643–50PubMedCrossRefGoogle Scholar
  86. 86.
    Abete P, Ferrara N, Cioppa A, et al. Preconditioning does not prevent postischemic dysfunction in aging heart. J Am Coll Cardiol 1996; 27: 1777–86PubMedCrossRefGoogle Scholar
  87. 87.
    Abete P, Testa G, Ferrara N, et al. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats. Am J Physiol Heart Circ Physiol 2002; 282: H1978–87PubMedGoogle Scholar
  88. 88.
    Fenton RA, Dickson EW, Meyer TE, et al. Aging reduces the cardioprotective effect of ischemic preconditioning in the rat heart. J Mol Cell Cardiol 2000; 32: 1371–5PubMedCrossRefGoogle Scholar
  89. 89.
    Tani M, Honma Y, Hasegawa H, et al. Direct activation of mitochondrial K(ATP) channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts. Cardiovasc Res 2001; 49: 56–68PubMedCrossRefGoogle Scholar
  90. 90.
    Tani M, Honma Y, Takayama M, et al. Loss of protection by hypoxic preconditioning in aging Fischer 344 rat hearts related to myocardial glycogen content and Na+ imbalance. Cardiovasc Res 1999; 41: 594–602PubMedCrossRefGoogle Scholar
  91. 91.
    Tani M, Suganuma Y, Hasegawa H, et al. Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts. Circulation 1997; 95: 2559–66PubMedCrossRefGoogle Scholar
  92. 92.
    Abete P, Cacciatore F, Testa G, et al. Ischemic preconditioning in the aging heart: from bench to bedside. Ageing Res Rev 2010; 9: 153–62PubMedCrossRefGoogle Scholar
  93. 93.
    Boengler K, Konietzka I, Buechert A, et al. Loss of ischemic preconditioning’s cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. Am J Physiol Heart Circ Physiol 2007; 292: H1764–9PubMedCrossRefGoogle Scholar
  94. 94.
    Boengler K, Buechert A, Heinen Y, et al. Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Circ Res 2008; 102: 131–5PubMedCrossRefGoogle Scholar
  95. 95.
    Przyklenk K, Maynard M, Darling CE, et al. Aging mouse hearts are refractory to infarct size reduction with post-conditioning. J Am Coll Cardiol 2008; 51: 1393–8PubMedCrossRefGoogle Scholar
  96. 96.
    Przyklenk K, Maynard M, Greiner D, et al. Cardioprotection with postconditioning: loss of efficacy in murine models of type-2 and type-1 diabetes. Antioxid Redox Signal 2011; 781–90Google Scholar
  97. 97.
    Willems L, Ashton KJ, Headrick JP. Adenosine-mediated cardioprotection in the aging myocardium. Cardiovasc Res 2005; 66: 245–55PubMedCrossRefGoogle Scholar
  98. 98.
    Mio Y, Bienengraeber MW, Marinovic J, et al. Age-related attenuation of isoflurane preconditioning in human atrial cardiomyocytes: roles for mitochondrial respiration and sarcolemmal adenosine triphosphate-sensitive potassium channel activity. Anesthesiology 2008; 108: 612–20PubMedCrossRefGoogle Scholar
  99. 99.
    Peart JN, Gross GJ. Chronic exposure to morphine produces a marked cardioprotective phenotype in aged mouse hearts. Exp Gerontol 2004; 39: 1021–6PubMedCrossRefGoogle Scholar
  100. 100.
    Sniecinski R, Liu H. Reduced efficacy of volatile anesthetic preconditioning with advanced age in isolated rat myocardium. Anesthesiology 2004; 100: 589–97PubMedCrossRefGoogle Scholar
  101. 101.
    Zhu J, Rebecchi MJ, Tan M, et al. Age-associated differences in activation of Akt/GSK-3beta signaling pathways and inhibition of mitochondrial permeability transition pore opening in the rat heart. J Gerontol A Biol Sci Med Sci 2010; 65: 611–9PubMedCrossRefGoogle Scholar
  102. 102.
    Yin Z, Gao H, Wang H, et al. Ischaemic post-conditioning protects both adult and aged Sprague-Dawley rat heart from ischaemia-reperfusion injury through the phosphatidylinositol 3-kinase-AKT and glycogen synthase kinase-3beta pathways. Clin Exp Pharmacol Physiol 2009; 36: 756–63PubMedCrossRefGoogle Scholar
  103. 103.
    Shinmura K, Nagai M, Tamaki K, et al. Gender and aging do not impair opioid-induced late preconditioning in rats. Basic Res Cardiol 2004; 99: 46–55PubMedCrossRefGoogle Scholar
  104. 104.
    McCully JD, Uematsu M, Parker RA, et al. Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart. Ann Thorac Surg 1998; 66: 2037–43PubMedCrossRefGoogle Scholar
  105. 105.
    Przyklenk K, Li G, Whittaker P. No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits. J Am Coll Cardiol 2001; 38: 1741–7PubMedCrossRefGoogle Scholar
  106. 106.
    Przyklenk K, Li G, Simkhovich BZ, et al. Mechanisms of myocardial ischemic preconditioning are age related: PKC-epsilon does not play a requisite role in old rabbits. J Appl Physiol 2003; 95: 2563–9PubMedGoogle Scholar
  107. 107.
    Burns PG, Krunkenkamp IB, Calderone CA, et al. Is the preconditioning response conserved in senescent myocardium? Ann Thorac Surg 1996; 61: 925–9PubMedCrossRefGoogle Scholar
  108. 108.
    Peart JN, Headrick JP. Sustained cardioprotection: exploring unconventional modalities. Vascul Pharmacol 2008; 49: 63–70PubMedCrossRefGoogle Scholar
  109. 109.
    Peart JN, See Hoe L, Gross GJ, et al. Sustained ligand-activated preconditioning via (delta)-opioid receptors. J Pharmacol Exp Ther 2011; 336: 274–81PubMedCrossRefGoogle Scholar
  110. 110.
    Korzick DH, Kostyak JC, Hunter JC, et al. Local delivery of PKCepsilon-activating peptide mimics ischemic preconditioning in aged hearts through GSK-3beta but not F1-ATPase inactivation. Am J Physiol Heart Circ Physiol 2007; 293: H2056–63PubMedCrossRefGoogle Scholar
  111. 111.
    Kersten JR, Toller WG, Tessmer JP, et al. Hyperglycemia reduces coronary collateral blood flow through a nitric oxide-mediated mechanism. Am J Physiol Heart Circ Physiol 2001; 281: H2097–104PubMedGoogle Scholar
  112. 112.
    Kristiansen SB, Lofgren B, Stottrup NB, et al. Ischaemic preconditioning does not protect the heart in obese and lean animal models of type 2 diabetes. Diabetologia 2004; 47: 1716–21PubMedCrossRefGoogle Scholar
  113. 113.
    Kersten JR, Toller WG, Gross ER, et al. Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality. Am J Physiol Heart Circ Physiol 2000; 278: H1218–24PubMedGoogle Scholar
  114. 114.
    Tsang A, Hausenloy DJ, Mocanu MM, et al. Preconditioning the diabetic heart: the importance of Akt phosphorylation. Diabetes 2005; 54: 2360–4PubMedCrossRefGoogle Scholar
  115. 115.
    Xu G, Takashi E, Kudo M, et al. Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway. Exp Mol Pathol 2004; 76: 57–65PubMedCrossRefGoogle Scholar
  116. 116.
    Bouhidel O, Pons S, Souktani R, et al. Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol 2008; 295: H1580–6PubMedCrossRefGoogle Scholar
  117. 117.
    Wagner C, Kloeting I, Strasser RH, et al. Cardioprotection by postconditioning is lost in WOKW rats with metabolic syndrome: role of glycogen synthase kinase 3beta. J Cardiovasc Pharmacol 2008; 52: 430–7PubMedCrossRefGoogle Scholar
  118. 118.
    Huhn R, Heinen A, Weber NC, et al. Hyperglycaemia blocks sevoflurane-induced postconditioning in the rat heart in vivo: cardioprotection can be restored by blocking the mitochondrial permeability transition pore. Br J Anaesth 2008; 100: 465–71PubMedCrossRefGoogle Scholar
  119. 119.
    Raphael J, Gozal Y, Navot N, et al. Hyperglycemia inhibits anesthetic-induced postconditioning in the rabbit heart via modulation of phosphatidylinositol-3-kinase/Akt and endothelial nitric oxide synthase signaling. J Cardiovasc Pharmacol 2010; 55: 348–57PubMedCrossRefGoogle Scholar
  120. 120.
    Huisamen B. Protein kinase B in the diabetic heart. Mol Cell Biochem 2003; 249: 31–8PubMedCrossRefGoogle Scholar
  121. 121.
    Mocanu MM, Field DC, Yellon DM. A potential role for PTEN in the diabetic heart. Cardiovasc Drugs Ther 2006; 20: 319–21PubMedCrossRefGoogle Scholar
  122. 122.
    Huhn R, Heinen A, Hollmann MW, et al. Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo. Nutr Metab Cardiovasc Dis 2010; 20: 706–12PubMedCrossRefGoogle Scholar
  123. 123.
    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: 37–45PubMedCrossRefGoogle Scholar
  124. 124.
    Ottani F, Galvani M, Ferrini D, et al. Prodromal angina limits infarct size: a role for ischemic preconditioning. Circulation 1995; 91: 291–7PubMedCrossRefGoogle Scholar
  125. 125.
    Ishihara M, Sato H, Tateishi H, et al. Implications of prodromal angina pectoris in anterior wall acute myocardial infarction: acute angiographic findings and long-term prognosis. J Am Coll Cardiol 1997; 30: 970–5PubMedCrossRefGoogle Scholar
  126. 126.
    Kloner RA, Shook T, Antman EM, et al. Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation 1998; 97: 1042–5PubMedCrossRefGoogle Scholar
  127. 127.
    Jenkins DP, Pugsley WB, Alkhulaifi AM, et al. Ischaemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. Heart 1997; 77: 314–8PubMedGoogle Scholar
  128. 128.
    Ghosh S, Galinanes M. Protection of the human heart with ischemic preconditioning during cardiac surgery: role of cardiopulmonary bypass. J Thorac Cardiovasc Surg 2003; 126: 133–42PubMedCrossRefGoogle Scholar
  129. 129.
    Kloner RA, Speakman MT, Przyklenk K. Ischemic preconditioning: a plea for rationally targeted clinical trials. Cardiovasc Res 2002; 55: 526–33PubMedCrossRefGoogle Scholar
  130. 130.
    Rezkalla SH, Kloner RA. Ischemic preconditioning and preinfarction angina in the clinical arena. Nat Clin Pract Cardiovasc Med 2004; 1: 96–102PubMedCrossRefGoogle Scholar
  131. 131.
    Rezkalla SH, Kloner RA. Preconditioning in humans. Heart Fail Rev 2007; 12: 201–6PubMedCrossRefGoogle Scholar
  132. 132.
    Piot C, Croisille P, Staat P, et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 2008; 359: 473–81PubMedCrossRefGoogle Scholar
  133. 133.
    Staat P, Rioufol G, Piot C, et al. Postconditioning the human heart. Circulation 2005; 112: 2143–8PubMedCrossRefGoogle Scholar
  134. 134.
    Darling CE, Solari PB, Smith CS, et al. ‘Postconditioning’ the human heart: multiple balloon inflations during primary angioplasty may confer cardioprotection. Basic Res Cardiol 2007; 102: 274–8PubMedCrossRefGoogle Scholar
  135. 135.
    Yang XC, Liu Y, Wang LF, et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J Invasive Cardiol 2007; 19: 424–30PubMedGoogle Scholar
  136. 136.
    Thibault H, Piot C, Staat P, et al. Long-term benefit of postconditioning. Circulation 2008; 117: 1037–44PubMedCrossRefGoogle Scholar
  137. 137.
    Ebrahim Z, Yellon DM, Baxter GF. Ischemic preconditioning is lost in aging hypertensive rat heart: independent effects of aging and longstanding hypertension. Exp Gerontol 2007; 42: 807–14PubMedCrossRefGoogle Scholar
  138. 138.
    Ishihara M, Inoue I, Kawagoe T, et al. Ischaemic preconditioning effect of prodromal angina pectoris is lost in patients with prior myocardial infarction. Heart 2006; 92: 973–4PubMedCrossRefGoogle Scholar
  139. 139.
    Ungi I, Ungi T, Ruzsa Z, et al. Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty. Chest 2005; 128: 1623–8PubMedCrossRefGoogle Scholar
  140. 140.
    Bolli R. Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. J Mol Cell Cardiol 2001; 33: 1897–918PubMedCrossRefGoogle Scholar
  141. 141.
    Brady PA, Terzic A. The sulfonylurea controversy: more questions from the heart. J Am Coll Cardiol 1998; 31: 950–6PubMedCrossRefGoogle Scholar
  142. 142.
    Jimenez-Navarro M, Gomez-Doblas JJ, Alonso-Briales J, et al. Does angina the week before protect against first myocardial infarction in elderly patients? Am J Cardiol 2001; 87: 11–5PubMedCrossRefGoogle Scholar
  143. 143.
    Kloner RA, Przyklenk K, Shook T, et al. Protection conferred by preinfarct angina is manifest in the aged heart: evidence from the TIMI 4 Trial. J Thromb Thrombolysis 1998; 6: 89–92PubMedCrossRefGoogle Scholar
  144. 144.
    Ishihara M, Inoue I, Kawagoe T, et al. Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction. J Am Coll Cardiol 2001; 38: 1007–11PubMedCrossRefGoogle Scholar
  145. 145.
    Abete P, Ferrara N, Cacciatore F, et al. Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart? J Am Coll Cardiol 1997; 30: 947–54PubMedCrossRefGoogle Scholar
  146. 146.
    Ishihara M, Sato H, Tateishi H, et al. Beneficial effect of prodromal angina pectoris is lost in elderly patients with acute myocardial infarction. Am Heart J 2000; 139: 881–8PubMedCrossRefGoogle Scholar
  147. 147.
    Wu ZK, Pehkonen E, Laurikka J, et al. The protective effects of preconditioning decline in aged patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2001; 122:972–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Cardiovascular Research Institute and Departments of Physiology and Emergency MedicineWayne State University School of MedicineDetroitUSA

Personalised recommendations