Skip to main content

Advertisement

SpringerLink
Log in

Postconditioning in Reperfusion Injury: A Status Report

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Early reperfusion after an organ ischemia is essential to salvage tissue from eventual death. However, abundant evidence suggests that reperfusion also elicits pathophysiological changes responsible for additional tissue injury after restoration of blood flow. Postconditioning (Postcon) defined as rapid sequential intermittent interruption of blood flow applied during early moments of reperfusion has successfully shown to attenuate organ injury, including the heart, spinal cord, brain, kidney, liver, muscle, lung and intestines in the experimental setting. Clinical trials have also revealed the beneficial effect of Postcon on myocardial infarction in patients undergoing percutaneous coronary intervention or coronary artery bypass graft surgery. Although there are some controversial issues regarding the efficacy of protection with Postcon in different animal models with comorbities, most preclinical studies have shown that Postcon is a potent intervention to reduce organ necrosis and apoptosis. Remote or pharmacological Postcon has emerged as alternatives in amelioration of cardiac reperfusion injury. This article will primarily discuss the existing literature regarding protection of Postcon on the heart, but there is a potential for future research into other organ systems to identify beneficial effects of Postcon on tissue reperfusion injury, particularly in patients undergoing surgical revascularization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Galinanes M, Fowler AG. Role of clinical pathologies in myocardial injury following ischaemia and reperfusion. Cardiovasc Res. 2004;61:512–21.

    Article  CAS  PubMed  Google Scholar 

  2. Di Carli MF, Asgarzadie F, Schelbert HR, Brunken RC, Laks H, et al. Quantitative relation between myocardial viability and improvement in heart failure symptoms after revascularization in patients with ischemic cardiomyopathy. Circulation. 1995;92:3436–44.

    PubMed  Google Scholar 

  3. Yellon DM, Opie LH. Postconditioning for protection of the infarcting heart. Lancet. 2006;367:456–8.

    Article  PubMed  Google Scholar 

  4. Bolli R, Becker L, Gross G, Mentzer Jr RM, Balshaw D, et al. Myocardial protection at a crossroads: the need for translation into clinical therapy. Circ Res. 2004;95:125–34.

    Article  CAS  PubMed  Google Scholar 

  5. Zhao Z-Q, Nakamura M, Wang N-P, Velez DA, Hewan-Lowe KO, et al. Dynamic progression of contractile and endothelial dysfunction and infarct extension in the late phase of reperfusion. J Surg Res. 2000;94:1–12.

    Article  Google Scholar 

  6. Gross GJ, Auchampach JA. Reperfusion injury: does it exist? J Mol Cell Cardiol. 2007;42:12–8.

    Article  CAS  PubMed  Google Scholar 

  7. Vinten-Johansen J, Yellon DM, Opie LH. A simple, clinically applicable procedure to improve revascularization in acute myocardial infarction. Circulation. 2005;112:2085–8.

    Article  PubMed  Google Scholar 

  8. Follette DM, Fey K, Buckberg GD, Helly Jr JJ, Steed DL, et al. Reducing postischemic damage by temporary modification of reperfusate calcium, potassium, pH, and osmolarity. J Thorac Cardiovasc Surg. 1981;82:221–38.

    CAS  PubMed  Google Scholar 

  9. Buckberg GD. Update on current techniques of myocardial protection. Ann Thorac Surg. 1995;60:805–14.

    Article  CAS  PubMed  Google Scholar 

  10. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest. 1985;76:1713–9.

    Article  CAS  PubMed  Google Scholar 

  11. Downey JM, Chone MV. Why do we still not have cardioprotective drugs? Circ J. 2009;73:1171–7.

    Article  PubMed  Google Scholar 

  12. Kloner RA, Rezkalla SH. Cardiac protection during acute myocardial infarction: where do we stand in 2004? J Am Coll Cardiol. 2004;44:276–86.

    Article  PubMed  Google Scholar 

  13. Zhao Z-Q, Corvera JS, Halkos ME, Kerendi F, Wang NP, et al. Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2003;285:H579–88.

    CAS  PubMed  Google Scholar 

  14. Diaz RJ, Wilson GJ. Modifying the first minute of reperfusion: potential for myocardial salvage. Cardiovasc Res. 2004;62:4–6.

    Article  CAS  PubMed  Google Scholar 

  15. Piper HM, Garcia-Dorado D, Ovize M. A fresh look at reperfusion injury. Cardiovasc Res. 1998;38:291–300.

    Article  CAS  PubMed  Google Scholar 

  16. Fujita M, Asanuma H, Hirata A, Wakeno M, Takahama H, et al. Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning. Am J Physiol Heart Circ Physiol. 2007;292:H2004–8.

    Article  CAS  PubMed  Google Scholar 

  17. Halkos ME, Kerendi F, Corvera JS, Wang NP, Kin H, et al. Myocardial protection with postconditioning is not enhanced by ischemic preconditioning. Ann Thorac Surg. 2004;78:961–9.

    Article  PubMed  Google Scholar 

  18. Gross GJ, Gauthier KM, Moore J, Campbell WB, Falck JR, et al. Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditionin and postconditioning in dog. Am J Physiol (Heart Circ Physiol). 2009;297:H47–52.

    Article  CAS  Google Scholar 

  19. Iliodromitis EK, Georgiadis M, Cohen MV, Downey JM, Bofilis E, et al. Protection from postconditioning depends on the number of short ischemic insults in anesthetized pigs. Basic Res Cardiol. 2006;101:502–7.

    Article  PubMed  Google Scholar 

  20. Yang XM, Liu Y, Tandon N, Kambayashi J, Downey JM, et al. Preconditioning in cynomolgus monkey heart protects aganist both ischemic aganist both ischemic and reperfusion injury. Circulation. 2009;118:S401.

    Google Scholar 

  21. Kin H, Zhao ZQ, Sun H-Y, Wang NP, Corvera JS, et al. Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 2004;62:74–85.

    Article  CAS  PubMed  Google Scholar 

  22. Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol. 2004;44:1103–10.

    Article  PubMed  Google Scholar 

  23. Xi L, Bader M, Zhao Z-Q, Das A, Kukreja RC. Loss of myocardial ischemic postcondditioning in adenosine A1 and bradykinin B2 receptors gene knockout mice. Circulation. 2008;118:32–7.

    Article  CAS  Google Scholar 

  24. Jin ZQ, Karliner JS, Vessey DA. Ischemic postconditioning protects isolated mouse hearts against ischemia/reperfusion injury via sphingosine kinase isoform-1 activation. Cardiovasc Res. 2008;79:134–40.

    Article  CAS  PubMed  Google Scholar 

  25. Sun H-Y, Wang NP, Kerendi F, Halkos M, Kin H, et al. Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca2+ overload. Am J Physiol Heart Circ Physiol. 2005;288:H1900–8.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao Z-Q, Sun H-Y, Wang N-P, Kin H, Guyton RA, et al. Hypoxic postconditioning attenuates cardiomyocyte apoptosis via inhibition of jnk and p38 kinases pathway. JMCC. 2005;38:870.

    Google Scholar 

  27. Dosenko VE, Nagibin VS, Tumanovskaya LV, Moibenko AA, Vaage J. Postconditioning prevents apoptotic necrotic and autophagic cardiomyocyte cell death in culture. Fiziol Zh. 2005;51:12–7.

    CAS  PubMed  Google Scholar 

  28. Dosenko VE, Nagibin VS, Tumanovskaya LV, Zagoriy VY, Moibenko AA, et al. Proteasome inhibitors eliminate protective effect of postconditioning in cultured neonatal cardiomyocytes. Fiziol Zh. 2006;52:15–24.

    CAS  PubMed  Google Scholar 

  29. Lu J, Zang WJ, Yu XJ, Jia B, Chorvatova A, et al. Effects of postconditioning of adenosine and acetylcholine on the ischemic isolated rat ventricular myocytes. Eur J Pharmacol. 2006;549:133–9.

    Article  CAS  PubMed  Google Scholar 

  30. Wang HC, Zhang HF, Guo WY, Su H, Zhang KR, et al. Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation. Apoptosis. 2006;11:1453–60.

    Article  CAS  PubMed  Google Scholar 

  31. Vinten-Johansen J, Zhao ZQ, Zatta AJ, Kin H, Halkos ME, et al. Postconditioning-A new link in nature’s armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol. 2005;100:295–310.

    Article  CAS  PubMed  Google Scholar 

  32. Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM. Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res. 2004;95:230–2.

    Article  CAS  PubMed  Google Scholar 

  33. Yang X-M, Proctor JB, Cui L, Krieg T, Downey JM, et al. Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol. 2004;44:1103–10.

    Article  PubMed  Google Scholar 

  34. Mykytenko J, Kerendi F, Reeves JG, Kin H, Zatta AJ, et al. Long-term inhibition of myocardial infarction by postconditioning during reperfusion. Basic Res Cardiol. 2007;102:90–100.

    Article  CAS  PubMed  Google Scholar 

  35. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, et al. Post-conditioning inhibits mitochondrial permeability transition. Circulation. 2005;111:194–7.

    Article  CAS  PubMed  Google Scholar 

  36. Skyschally A, Caster PV, Iliodromitis EK, Schulz R, Kremastinos AT, et al. Ischemic postconditioning: experimental models and protocol algorithms. Basic Res Cardiol. 2009;104:469–83.

    Article  PubMed  Google Scholar 

  37. Schwartz LM, Lagranha CJ. Ischemic postconditioning during reperfusion activates Akt and ERK without protecting against lethal myocardial ischemia-reperfusion injury in pigs. Am J Physiol Heart Circ Physiol. 2006;290:H1011–8.

    Article  CAS  PubMed  Google Scholar 

  38. Dow J, Kloner RA. Postconditioning does not reduce myocardial infarct size in an in vivo regional ischemia rodent model. J Cardiovasc Pharmacol Ther. 2007;12:153–63.

    Article  PubMed  Google Scholar 

  39. Hale SL, Mehra A, Leeka J, Kloner RA. Postconditioning fails to improve no reflow or alter infarct size in an open-chest rabbit model of myocardial ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2008;294:H421–5.

    Article  CAS  PubMed  Google Scholar 

  40. Granfeldt A, Lefer DJ, Vinten-Johansen J. Protective ischemia in patients: preconditioning and postconditioning. Cardiovasc Res. 2009;83:234–46.

    Article  CAS  PubMed  Google Scholar 

  41. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M. Post-conditioning inhibits mitochondrial permeability transition. Circulation. 2005;111:194–7.

    Article  CAS  PubMed  Google Scholar 

  42. Darling C, Maynard M, Przyklenk K. Post-conditioning via stuttering reperfusion limits myocardial infarct size in rabbit heart. Acad Emerg Med. 2004;11:536-a.

    Article  Google Scholar 

  43. Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K. Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol. 2005;289:H1618–26.

    Article  CAS  PubMed  Google Scholar 

  44. Iliodoromitis EK, Downey JM, Heusch G, Kremastinos DT. What is the optimal postconditioning algorithm? J Cardiovasc Pharmacol Ther. 2009;14:269–73.

    Article  Google Scholar 

  45. Yin Z, Gao H, Wang H, Li L, Di C, et al. Ischemic postconditioning protects coth adult and aged Sprague Dawley rat hearts from ischemia/reperfusion injury through the PI3-K/Akt and GSK-beta pathway. Exp Pharmacol Physiol. 2009, [Epub ahead of print].

  46. Przyklenk K, Mayne M, Darling C, Whittaker P. Aging mouse hearts are refractory to infarct size reduction with post-conditioning. J Am Coll Cardiol. 2009;51:1393–8.

    Article  Google Scholar 

  47. Boengler K, Buechert A, Heinen Y, Roeskes C, Hilfiker-Kleiner D, et al. Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Circ Res. 2008;102:131–5.

    Article  CAS  PubMed  Google Scholar 

  48. Donato M, Dannunzio V, Berg G, Gonzalez G, Schreier L, et al. Ischemic postconditioning reduces infarct size by activation of A1 receptors and K+ATP channels in both normal and hypercholesterolemic rabbits. J Cardiovasc Pharmacol. 2007;49:287–92.

    Article  CAS  PubMed  Google Scholar 

  49. Iliodromitis EK, Zoga A, Vrettou A, Andreadou I, Paraskevaidis IA, et al. The effectiveness of postconditioning and preconditioning on infarct size in hypercholesterolemic and normal anesthetized rabbits. Atherosclerosis. 2006;188:356–62.

    Article  CAS  PubMed  Google Scholar 

  50. Abbott RD, Donahue RP, Kannel WB, Wilson PW. The impact of diabetes on survival following myocardial infarction in men vs women. J Am Med Assoc. 1988;260:3456–60.

    Article  CAS  Google Scholar 

  51. Bouhidel O, Pons S, Souktani R, Zini R, Berdeaux A, et al. Myocardial ischemic postconditioning against ischemia/reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol. 2009;295:H1508–86.

    Google Scholar 

  52. Wagner C, Kloeting I, Strasser RH, Weinbrenner C. Cardioprotection by postconditioning is lost in WOKW rats with metabolic syndrome: role of glycogen synthase kinase 3 beta. J Cardiovasc Pharmacol. 2008;52:430–7.

    Article  CAS  PubMed  Google Scholar 

  53. Prazklenk K, Maynard M, Greiner DL, Whittaker P. Restoration of normaglycemia re-establishes the infarct-sparing effect of postconditioning in diabetic mice. Circulation. 2008;118:S-403.

    Google Scholar 

  54. Na HS, Kim YI, Yoon YW, Han HC, Nahm SH, et al. Ventricular premature beat-driven intermittent restoration of coronary blood flow reduces the incidence of reperfusion-induced ventricular fibrillation in a cat model of regional ischemia. Am Heart J. 1996;132:78–83.

    Article  CAS  PubMed  Google Scholar 

  55. Kloner RA, Rezkalla SH. Preconditioning, postconditioning and their application to clinical cardiology. Cardiovasc Res. 2006;70:297–307.

    Article  CAS  PubMed  Google Scholar 

  56. Galagudza M, Kurapeev D, Minasian S, Valen G, Vaage J. Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm. Eur J Cardiothorac Surg. 2004;25:1006–10.

    Article  PubMed  Google Scholar 

  57. Kloner RA, Dow J, Bhandari A. Postconditioning markedly attenuates ventricular arrhythmias after ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2006;11:55–63.

    Article  PubMed  Google Scholar 

  58. Dow J, Bhandari A, Kloner RA. Ischemic postconditioning’s benefit on reperfusion ventricular arrhythmias is maintained in the senescent heart. J Cardiovasc Pharmacol Ther. 2008;13:141–8.

    Article  PubMed  Google Scholar 

  59. Yang XM, Philipp S, Downey JM, Cohen MV. 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.

    Article  CAS  PubMed  Google Scholar 

  60. Vinten-Johansen J, Zhao Z-Q, Zatta AJ, Kin H, Halkos ME, et al. Postconditioning a new link in nature’s armor against myocardial ischemia-reperfusion injury. Basic Res Cardiol. 2005;100:1–16.

    Article  Google Scholar 

  61. Zhao Z-Q, Nakamura M, Wang N-P, Wilcox JN, Shearer ST, et al. Reperfusion-induced apoptosis progressively develops in later stages of reflow. Apoptosis. 2001;6:279–90.

    Google Scholar 

  62. Serviddio G, Di Venosa N, Federici A, D’Agostino D, Rollo T, et al. Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion. FASEB J. 2005;19:354–61.

    Article  CAS  PubMed  Google Scholar 

  63. Sun H-Y, Wang NP, Halkos M, Kerendi F, Kin H, et al. Postconditioning attenuates cardiomyocyte apoptosis via inhibition of JNK and p38 mitogen-activated protein kinase signaling pathways. Apoptosis. 2006;11:1583–93.

    Article  CAS  PubMed  Google Scholar 

  64. Penna C, Cappello S, Mancardi D, Raimondo S, Rastaldo R, et al. Post-conditioning reduces infarct size in the isolated rat heart: role of coronary flow and pressure and the nitric oxide/cGMP pathway. Basic Res Cardiol. 2006;101:168–79.

    Article  CAS  PubMed  Google Scholar 

  65. Kin H, Wang N-P, Corvera J, Guyton RA, Vinten-Johansen J, Zhao Z-Q. Inhibition of myocardial apoptosis by postconditioning is associated with attenuation of oxidative stress-mediated NFκB translocation and cytokine release. Shock. 2008;29:761–8.

    CAS  PubMed  Google Scholar 

  66. Hansen PR, Thibault H., Abdulla J. Postconditioning during primary percataneous coronary intervention: a review and meta-analysis. Int J Cardiol. 2009, (Epub ahead of print).

  67. Laskey WK. Brief repetitive balloon occlusions enhance reperfusion during percutaneous coronary intervention for acute myocardial infarction: a pilot study. Catheter Cardiovasc Interv. 2005;65:361–7.

    Article  PubMed  Google Scholar 

  68. Laskey WK, Yoon S, Calzada N, Ricciardi MJ. Concordant improvements in coronary flow reserve and ST-segment resolution during percutaneous coronary intervention for acute myocardial infarction: a benefit of postconditioning. Catheter Cardiovasc Interv. 2008;72:212–20.

    Article  PubMed  Google Scholar 

  69. Staat P, Rioufol G, Piot C, Cottin Y, Cung TT, et al. Postconditioning the human heart. Circulation. 2005;112:2143–8.

    Article  PubMed  Google Scholar 

  70. Ma X, Zhang X, Li C, Luo M. Effect of postconditioning on coronary blood flow velocity and endothelial function and LV recovery after myocardial infarction. J Interv Cardiol. 2006;19:367–75.

    Article  PubMed  Google Scholar 

  71. Darling CE, Solari PB, Smith CS, Furman MI, Przyklenk K. ‘Postconditioning’ the human heart: multiple balloon inflations during primary angioplasty may confer cardioprotection. Basic Res Cardiol. 2007;102:274–8.

    Article  PubMed  Google Scholar 

  72. Wang G, Zhang S, Joggerst SJ, Mcpherson J, Zhao DX. Effects of the number and interval of balloon inflations during primary PCI on the extent of myocardial injury in patients with STEMI: does postconditioning exist in real-world practice? J Invasive Cardiol. 2009;21:451–5.

    CAS  PubMed  Google Scholar 

  73. Ono K, Matsumori A, Shioi T, Furukawa Y, Sasayama S. Cytokine gene expression after myocardial infarction in rat hearts. Possible implication in left ventricular remodeling. Circulation. 1998;98:149–56.

    CAS  PubMed  Google Scholar 

  74. Yang XC, Liu Y, Wang LF, Cui L, Wang T, et al. Reduction in myocardial infarct size by postconditioning in patients after percutaneous coronary intervention. J Invasive Cardiol. 2007;19:424–30.

    PubMed  Google Scholar 

  75. Thibault H, Piot C, Staat P, Bontemps L, Sportouch C, et al. Long-term benefit of postconditioning. Circulation. 2008;117:1037–44.

    Article  CAS  PubMed  Google Scholar 

  76. Zhao WS, Xu L, Wang LF, Zhang L, Zhang ZY, et al. A 60-s postconditioning protocol by percutaneous coronary intervention inhibits myocardial apoptosis in patients with acute myocardial infarction. Apoptosis. 2009;14:1204–11.

    Article  PubMed  Google Scholar 

  77. Luo W, Li B, Lin G, Huang R. Postconditioning in cardiac surgery for tetralogy of Fallot. J Thorac Cardiovasc Surg. 2007;133:1373–4.

    Article  PubMed  Google Scholar 

  78. Luo W, Li B, Chen R, Huang R, Lin G. Effect of ischemic postconditioning in adult valve replacement. Eur J Cardiothorac Surg. 2008;33:203–8.

    Article  PubMed  Google Scholar 

  79. Kin H, Zatta AJ, Lofye MT, Amerson BS, Halkos ME, et al. Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res. 2005;67:124–33.

    Article  CAS  PubMed  Google Scholar 

  80. Kin H, Zatta AJ, Jiang R, Reeves JG, Zhao Z-Q, et al. Activation of opioid receptors mediates the infarct size reduction by postconditioning. JMCC. 2005;38:827.

    Google Scholar 

  81. Gross ER, Gross GJ. Ligand triggers of classical preconditioning and postconditioning. Cardiovasc Res. 2006;70:212–21.

    Article  CAS  PubMed  Google Scholar 

  82. Zatta AJ, Kin H, Yoshishige D, Jiang R, Wang N, et al. Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Am J Physiol Heart Circ Physiol. 2008;294:H1444–51.

    Article  CAS  PubMed  Google Scholar 

  83. Zatta AJ, Kin H, Lee G, Wang N, Jiang R, et al. Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling. Cardiovasc Res. 2006;70:315–24.

    Article  CAS  PubMed  Google Scholar 

  84. Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M. Inhibition of GSK3B by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation. 2008;117:2761–8.

    Article  CAS  PubMed  Google Scholar 

  85. Cohen MV, Yang XM, Downey JM. The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation. 2007;115:1895–903.

    Article  PubMed  Google Scholar 

  86. Mykytenko J, Reeves JG, Kin H, Zatta AJ, Zhao Z-Q. Persistent beneficial effect of postconditioning aganist infarct size: role of mitochondrial KATP channel activation during reperfusion. Basic Res Cardiol. 2008;103:472–84.

    Article  CAS  PubMed  Google Scholar 

  87. Jiang R, Zatta AJ, Kin H, Wang N, Zhao ZQ, et al. PAR2 activation at the time of reperfusion salvages myocardium via an ERK 1/2 pathway in in vivo rat hearts. Am J Physiol Heart Circ Physiol. 2007;293:H2845–52.

    Article  CAS  PubMed  Google Scholar 

  88. Ghosh PM, Bedolla R, Thomas CA, Kreisberg JI. Role of protein kinase C in arginine vasopressin-stimulated ERK and p70S6 kinase phosphorylation. J Cell Biol. 2004;91:1109–29.

    CAS  Google Scholar 

  89. Ping P. A new chapter in cardiac PKC signaling studies: searching for isoform-specific molecular targets. Focus on: “Isoenzyme-selective regulation of SERCA2 gene expression by protein kinase C in neonatal rat ventricular myocytes”. Am J Physiol Cell Physiol. 2003;285:C19–21.

    CAS  PubMed  Google Scholar 

  90. Sims NR, Anderson MF. Mitochondrial contributions to tissue damage in stroke. Neurochem Int. 2002;40:511–26.

    Article  CAS  PubMed  Google Scholar 

  91. Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res. 2004;61:372–85.

    Article  CAS  PubMed  Google Scholar 

  92. Murata M, Akao M, O’Rourke B, Marban E. Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. Circ Res. 2001;89:891–8.

    Article  CAS  PubMed  Google Scholar 

  93. Chen M, Won D-J, Krajewski S, Gottlieb RA. Calpain and mitochondria in ischemia/reperfusion injury. J Biol Chem. 2002;277:29181–6.

    Article  CAS  PubMed  Google Scholar 

  94. Mukherjee SB, Das M, Sudhandiran G, Shaha C. Increase in cytosolic Ca2+ levels through the activation of non-selective cation channels induced by oxidative stress causes mitochondrial depolarization leading to apoptosis-like death in Leishmania donovani promastigotes. J Biol Chem. 2002;277:24717–27.

    Article  CAS  PubMed  Google Scholar 

  95. Mathiasen IS, Sergeev IN, Bastholm L, Elling F, Norman AW, Jaattela M. Calcium and calpain as key mediators of apoptosis-like death induced by vitamin d compounds in breast cancer cells. J Biol Chem. 2002;277:30738–45.

    Article  CAS  PubMed  Google Scholar 

  96. Krolikowski JG, Bienengraeber MW, Weihrauch D, Warltier DC, Kersten JR, Pagel PS. Inhibition of mitochondrial permeability transition enchances isoflurance-induced cardioprotection during early reperfusion: the role of mitochondrial KATP channels. Anesth Analg. 2005;101:1590–6.

    Article  CAS  PubMed  Google Scholar 

  97. Pain T, Yang X-M, Critz SD, Yue Y, Nakano A, Liu GS, et al. Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals. Circ Res. 2000;87:460–6.

    CAS  PubMed  Google Scholar 

  98. Gateau-Roesch O, Argaud L, Ovize M. Mitochondrial permeability transition pore and postconditioning. Cardiovasc Res. 2006;70:264–73.

    Article  CAS  PubMed  Google Scholar 

  99. Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med. 2008;359:473–81.

    Article  CAS  PubMed  Google Scholar 

  100. Kerendi F, Kin H, Halkos ME, Jiang R, Zatta AJ, Zhao ZQ, et al. Remote postconditioning. Brief renal ischemia and reperfusion applied before coronary artery reperfusion reduces myocardial infarct size via endogenous activation of adenosine receptors. Basic Res Cardiol. 2005;100:404–12.

    Article  CAS  PubMed  Google Scholar 

  101. Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, et al. Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs. Heart. 2007;93:749–52.

    Article  PubMed  Google Scholar 

  102. Loukogeorgakis SP, Panagiotidou AT, Yellon DM, Deanfield JE, MacAllister RJ. Postconditioning protects against endothelial ischemia-reperfusion injury in the human forearm. Circulation. 2006;113:1015–9.

    Article  PubMed  Google Scholar 

  103. Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, et al. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007;116:1386–95.

    Article  CAS  PubMed  Google Scholar 

  104. Jiang X, Shi E, Nakajima Y, Sato S. Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia. Ann Surg. 2006;244:148–53.

    Article  PubMed  Google Scholar 

  105. Jiang X, Shi E, Nakajima Y, Sato S. Co-application of ischemic preconditioning and postconditioning provides additive neuroprotection against spinal cord ischemia in rabbits. Life Sci. 2008;82:608–14.

    Article  CAS  PubMed  Google Scholar 

  106. Song WY, Dong HL, Cheng Q, Lu ZH, Wang H, et al. Ischemic postconditioning induces neuroprotection via up-regulation of endogenous antioxidant enzyme activities: experiment with rabbits. Chung-Hua Yi Hsueh Tsa Chih. 2008;88:2355–9.

    CAS  Google Scholar 

  107. Wang JY, Shen J, Gao Q, Ye ZG, Yang SY, et al. Ischemic postconditioning protects against global cerebral ischemia/reperfusion-induced injury in rats. Stroke. 2008;39:983–90.

    Article  PubMed  Google Scholar 

  108. Danielisova V, Nemethova M, Gottlieb M, Burda J. The changes in endogenous antioxidant enzyme activity after postconditioning. Cell Mol Neurobiol. 2006;26:1181–91.

    Article  CAS  PubMed  Google Scholar 

  109. Xing BZ, Chen H, Zhang M, Zhao D, Jiang R, et al. Ischemic postconditioning inhibits apoptosis after focal cerebral ischemia/reperfusion in the rat. Stroke. 2008;39:2362–9.

    Article  CAS  PubMed  Google Scholar 

  110. Burda J, Danielisova V, Nemethova M, Gottlieb M, Matiasova M, et al. Delayed postconditioning initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain. Cell Mol Neurobiol. 2006;1141–51.

  111. Zhao H, Sapolsky RM, Steinberg GK. Interrupting reperfusion as a stroke therapy: ischemic postconditioning reduces infarct size focal ischemia in rats. J Cereb Blood Flow Metab. 2006;26:1114–21.

    Article  CAS  PubMed  Google Scholar 

  112. Zhao H. Ischemic postconditioning as a novel avenue to protect against brain injury after stroke. J Cereb Blood Flow Metab. 2009, [Epub ahead of print].

  113. Ren C, Gao X, Niu G, Yan Z, Chen X, Zhao H. Delayed of neurosurgery. PLoS ONE [Electronic Resource]. 2008;3:e3851.

    Article  CAS  Google Scholar 

  114. Szwarc I, Soullier S, Gayrard N, Mejean C, Mourad G, Argiles A. Ischemic postconditioning prevents ischemic acute renal failure. Transplant Proc. 2007;39:2554–6.

    Article  CAS  PubMed  Google Scholar 

  115. Liu X, Chen H, Zhan B, Xing B, Zhou J, Zhu H, et al. Attenuation of reperfusion injury by renal ischemic postconditioning: the role of NO. Biochem Biophys Res Commun. 2007;359:628–34.

    Article  CAS  PubMed  Google Scholar 

  116. Serviddio G, Romano AD, Gesualdo L, Tamborra R, Di Palma AM, et al. Vendemaile G postconditioning is any effective strategy to reduce renal ischaemia/reperfusion injury. Nephrol Dial Transplant. 2008;23:1504–12.

    Article  PubMed  Google Scholar 

  117. Chen H, Xing B, Liu X, Zhan B, Zhou J, Zhu H, Chen Z. Ischemic postconditioning inhibits apoptosis after renal ischemia/reperfusion injury in rat. Transpl Int. 2008;21(4):364–71:364–367.

    Google Scholar 

  118. Yun Y, Duan WG, When P, Wu HX, Shen ZQ. Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats. Transplant Proc. 2009;41:3597–602.

    Article  CAS  PubMed  Google Scholar 

  119. Eldaif SM, Deneve JA, Wang NP, Jiang R, Mousunjac M, Mutrie CJ, et al. Attenuation of renal ischemia/reperfusion injury by postconditioning involves adenosine receptor and PKC activation. Transpl Int. 2009, [Epub ahead of print].

  120. Sivaraman V, Mudalagiri NR, Di Salvo C, Kolvekar S, Hayward M, et al. Postconditioning protects human atrial muscle through the activation of the RISK pathway. Basic Res Cardiol. 2007;102:453–9.

    Article  PubMed  Google Scholar 

  121. McAllister SE, Ashrafpour H, Cahoon N, Huang N, Moses MA, et al. Postconditioning for salvage of ischemic skeletal muscle from reperfusion injury: efficacy and mechanism. Am J Physiol Regul Integr Comp Physiol. 2008;295:R681–9.

    CAS  PubMed  Google Scholar 

  122. Szijarto A, Gyurkovics E, Aranyi P, Onody P, Stangl R, Tatrai M, et al. Effects of postconditioning in major vascular operations on rats [Hungarian]. Magy Seb. 2009;62:187.

    Google Scholar 

  123. Sun K, Liu ZS, Sun Q. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusioln injury and protective effect of ischemic postconditioning. World J Gastroenterol. 2004;10:1934–8.

    PubMed  Google Scholar 

  124. Wang N, Lu J, He XL, Li N, Qiao Q, et al. Effects of ischemic postconditioning on reperfusion injury in rat liver grafts after orthotopic liver transplantation. Japan Society of Hepatology. 2009;39:382–90.

    CAS  Google Scholar 

  125. Wu B, Chu WW, Zhang LY, Wang P, Ma QY, et al. Protection of preconditioning, postconditioning and combined therapy against hepatic ischemia/reperfusion injury. Chinese Journal of Traumatology. 2007;10:223–7.

    CAS  PubMed  Google Scholar 

  126. Wang KX, Hu SY, Jiang XS, Zhu M, Jin B, et al. Protective effect of ischaemic postconditioning on warm/cold ischemic reperfusion injury in rat liver: comparative study with ischaemic preconditioning. Chin Med J (Engl). 2008;121:2004–9.

    Google Scholar 

  127. Xia ZY, Gao J, Anacharaz AK. Protective effect of ischemic postconditioning on lung ischemia-reperfusion injury in rats and the role of heme oxygenase-1. Chin J Traumatol. 2009;12:162–6.

    CAS  PubMed  Google Scholar 

  128. Liu KX, Li YS, Huang WQ, Li C, Liu JX, et al. Immediate but not delayed postconditioning during reperfusion attenuates acute lung injury induced by intestinal ischemia/reperfusion in rats: comparison with ischemic preconditioning. J Surg Res. 2009;157:55–62.

    Article  CAS  Google Scholar 

  129. Santos CH, Gomes OM, Pontes JC, Miiji LN, Bispo MA. The ischemic preconditioning and postconditioning effect on the intestinal mucosa of rats undergoing mesenteric ischemia/reperfusion procedure. Acta Cir Bras. 2008;23:22–8.

    PubMed  Google Scholar 

  130. Liu KX, Li YS, Huang WQ, Chen SQ, Wang ZX, et al. Immediate postconditioning during reperfusion attenuates intestinal injury. Intensive Care Med. 2009;35:933–42.

    Article  PubMed  Google Scholar 

  131. Tang X-L, Sato H, Tiwari S, Dawn B, Bi Q, et al. Cardioprotection by postconditioning in conscious rats is limited to coronary occlusions <45 minutes. Am J Physiol (Heart Circ Physiol). 2006;291:H2308–17.

    Article  CAS  Google Scholar 

  132. Koerner MJ. Good news for donor hearts: postconditioning. Transplantation. 2009;84:1382–3.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA, USA

    Zhi-Qing Zhao

  2. Department of Basic Biomedical Sciences, Mercer University School of Medicine, 4700 Waters Avenue, Savannah, GA, 31404, USA

    Zhi-Qing Zhao

Authors
  1. Zhi-Qing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhi-Qing Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhao, ZQ. Postconditioning in Reperfusion Injury: A Status Report. Cardiovasc Drugs Ther 24, 265–279 (2010). https://doi.org/10.1007/s10557-010-6240-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-010-6240-1

Key words

Search

Navigation