Top

Published in:

01-06-2010

Mechanism of Cardioprotection by Early Ischemic Preconditioning

Authors: Xiulan Yang, Michael V. Cohen, James M. Downey

Published in: Cardiovascular Drugs and Therapy | Issue 3/2010

Abstract

A series of brief ischemia/reperfusion cycles (termed ischemic preconditioning, IPC) limits myocardial injury produced by a subsequent prolonged period of coronary artery occlusion and reperfusion. Over the last 2 decades our understanding of IPC’s mechanism has increased exponentially. Hearts exposed to IPC have a better metabolic and ionic status during prolonged ischemia compared to naïve hearts. However, this difference is not thought to be the main mechanism by which IPC protects against infarction. Signaling pathways that are activated by IPC distinguish IPC hearts from naïve hearts. During the trigger phase of IPC, adenosine, bradykinin and opioid receptors are occupied. Although these three receptors trigger signaling through divergent pathways, the signaling converges on protein kinase C. We have proposed that at the end of the index ischemia the activated PKC sensitizes the low-affinity A_2b adenosine receptor (A_2bAR) through phosphorylation of either the receptor or its coupling proteins so that A_2bAR can be activated by endogenous adenosine released by the previously ischemic cardiomyocytes. The sensitized A_2bAR would then be responsible for activation of the survival kinases including PI3 kinase, Akt and ERK which then act to inhibit lethal mitochondrial permeability transition pore formation which normally uncouples mitochondria and destroys many myocytes in the first minutes of reperfusion. Herein we review the evidence for the above mechanisms and their functional details.

Cohen MV, Downey JM. Myocardial preconditioning promises to be a novel approach to the treatment of ischemic heart disease. Annu Rev Med. 1996;47:21–9.PubMedCrossRef

Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124–36.PubMed

Murry CE, Richard VJ, Jennings RB, Reimer KA. Myocardial protection is lost before contractile function recovers from ischemic preconditioning. Am J Physiol. 1991;260:H796–804.PubMed

Jennings RB, Sebbag L, Schwartz LM, et al. Metabolism of preconditioned myocardium: effect of loss and reinstatement of cardioprotection. J Mol Cell Cardiol. 2001;33:1571–88.PubMedCrossRef

Fleet WF, Johnson TA, Graebner CA, Gettes LS. Effect of serial brief ischemic episodes on extracellular K⁺, pH, and activation in the pig. Circulation. 1985;72:922–32.PubMed

Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res. 1990;66:913–31.PubMed

Soares PR, de Albuquerque CP, Chacko VP, et al. Role of preischemic glycogen depletion in the improvement of postischemic metabolic and contractile recovery of ischemia-preconditioned rat hearts. Circulation. 1997;96:975–83.PubMed

Miura T, Suzuki K, Shimamoto K, Iimura O. Suppression of the degradation of adenine nucleotides during ischemia may not be a sufficient mechanism for infarct size limitation by preconditioning. Basic Res Cardiol. 1996;91:425–32.PubMedCrossRef

Weinbrenner C, Wang P, Downey JM. Loss of glycogen during preconditioning is not a prerequisite for protection of the rabbit heart. Basic Res Cardiol. 1996;91:374–81.PubMed

10.

Yang X-M, Liu Y, Liu Y, et al. Attenuation of infarction in cynomolgus monkeys: preconditioning and postconditioning. Basic Res Cardiol. 2010;105:119–28.PubMedCrossRef

11.

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;61:448–60.PubMedCrossRef

12.

Solenkova NV, Solodushko V, Cohen MV, Downey JM. Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt. Am J Physiol. 2006;290:H441–9.

13.

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

14.

Förster K, Paul I, Solenkova N, et al. NECA at reperfusion limits infarction and inhibits formation of the mitochondrial permeability transition pore by activating p70S6 kinase. Basic Res Cardiol. 2006;101:319–26.PubMedCrossRef

15.

Methner C, Donat U, Felix SB, Krieg T. Cardioprotection of bradykinin at reperfusion involves transactivation of the epidermal growth factor receptor via matrix metalloproteinase-8. Acta Physiol. 2009;197:265–71.CrossRef

16.

Liu GS, Thornton J, Van Winkle DM, et al. Protection against infarction afforded by preconditioning is mediated by A₁ adenosine receptors in rabbit heart. Circulation. 1991;84:350–6.PubMed

17.

Wall TM, Sheehy R, Hartman JC. Role of bradykinin in myocardial preconditioning. J Pharmacol Exp Ther. 1994;270:681–9.PubMed

18.

Schultz JEJ, Rose E, Yao Z, Gross GJ. Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol. 1995;268:H2157–61.PubMed

19.

Goto M, Liu Y, Yang X-M, et al. Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res. 1995;77:611–21.PubMed

20.

Cohen MV, Yang X-M, Liu GS, et al. Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial K_ATP channels. Circ Res. 2001;89:273–8.PubMedCrossRef

21.

Cohen MV, Philipp S, Krieg T, et al. Preconditioning-mimetics bradykinin and DADLE activate PI3-kinase through divergent pathways. J Mol Cell Cardiol. 2007;42:842–51.PubMedCrossRef

22.

Oldenburg O, Qin Q, Krieg T, et al. Bradykinin induces mitochondrial ROS generation via NO, cGMP, PKG, and mitoK_ATP channel opening and leads to cardioprotection. Am J Physiol. 2004;286:H468–76.

23.

Banerjee A, Locke-Winter C, Rogers KB, et al. Preconditioning against myocardial dysfunction after ischemia and reperfusion by an α₁-adrenergic mechanism. Circ Res. 1993;73:656–70.PubMed

24.

Liu Y, Tsuchida A, Cohen MV, Downey JM. Pretreatment with angiotensin II activates protein kinase C and limits myocardial infarction in isolated rabbit hearts. J Mol Cell Cardiol. 1995;27:883–92.PubMedCrossRef

25.

Wang P, Gallagher KP, Downey JM, Cohen MV. Pretreatment with endothelin-1 mimics ischemic preconditioning against infarction in isolated rabbit heart. J Mol Cell Cardiol. 1996;28:579–88.PubMedCrossRef

26.

Kennedy S, Kane KA, Pyne NJ, Pyne S. Targeting sphingosine-1-phosphate signalling for cardioprotection. Curr Opin Pharmacol. 2009;9:194–201.PubMedCrossRef

27.

Murry CE, Richard VJ, Jennings RB, Reimer KA. Preconditioning with ischemia: is the protective effect mediated by free radical-induced myocardial stunning? Circulation. 1988;78(Suppl II):II-77.

28.

Baines CP, Goto M, Downey JM. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol. 1997;29:207–16.PubMedCrossRef

29.

Tritto I, D’Andrea D, Eramo N, et al. Oxygen radicals can induce preconditioning in rabbit hearts. Circ Res. 1997;80:743–8.PubMed

30.

Vanden Hoek TL, Becker LB, Shao Z, et al. Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem. 1998;273:18092–8.CrossRef

31.

Kuno A, Solenkova NV, Solodushko V, et al. Infarct limitation by a protein kinase G activator at reperfusion in rabbit hearts is dependent on sensitizing the heart to A_2b agonists by protein kinase C. Am J Physiol. 2008;295:H1288–95.

32.

Liu Y, Yang X-M, Iliodromitis EK, et al. Redox signaling at reperfusion is required for protection from ischemic preconditioning but not from a direct PKC activator. Basic Res Cardiol. 2008;103:54–9.PubMedCrossRef

33.

Korichneva I, Hoyos B, Chua R, et al. Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen. J Biol Chem. 2002;277:44327–31.PubMedCrossRef

34.

Kevin LG, Camara AKS, Riess ML, et al. Ischemic preconditioning alters real-time measure of O₂ radicals in intact hearts with ischemia and reperfusion. Am J Physiol. 2003;284:H566–74.

35.

Becker LB. New concepts in reactive oxygen species and cardiovascular reperfusion physiology. Cardiovasc Res. 2004;61:461–70.PubMedCrossRef

36.

Carroll R, Gant VA, Yellon DM. Mitochondrial K_ATP channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation. Cardiovasc Res. 2001;51:691–700.PubMedCrossRef

37.

Forbes RA, Steenbergen C, Murphy E. Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res. 2001;88:802–9.PubMedCrossRef

38.

Costa ADT, Jakob R, Costa CL, et al. The mechanism by which the mitochondrial ATP-sensitive K⁺ channel opening and H₂O₂ inhibit the mitochondrial permeability transition. J Biol Chem. 2006;281:20801–8.PubMedCrossRef

39.

Bolli R, Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion: evidence that myocardial “stunning” is a manifestation of reperfusion injury. Circ Res. 1989;65:607–22.PubMed

40.

Costa ADT, Garlid KD, West IC, et al. Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ Res. 2005;97:329–36.PubMedCrossRef

41.

Costa ADT, Garlid KD. Intramitochondrial signaling: interactions among mitoK_ATP, PKCε, ROS, and MPT. Am J Physiol. 2008;295:H874–82.

42.

Oldenburg O, Qin Q, Sharma AR, et al. Acetylcholine leads to free radical production dependent on K_ATP channels, G_i proteins, phosphatidylinositol 3-kinase and tyrosine kinase. Cardiovasc Res. 2002;55:544–52.PubMedCrossRef

43.

Miro-Casas E, Ruiz-Meana M, Agullo E, et al. Connexin43 in cardiomyocyte mitochondria contributes to mitochondrial potassium uptake. Cardiovasc Res. 2009;83:747–56.PubMedCrossRef

44.

Heinzel FR, 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;97:583–6.PubMedCrossRef

45.

Bell RM, Cave AC, Johar S, et al. Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning. FASEB J. 2005;19:2037–9.PubMed

46.

Ytrehus K, Liu Y, Downey JM. Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol. 1994;266:H1145–52.PubMed

47.

Dorn GW 2nd, Souroujon MC, Liron T, et al. Sustained in vivo cardiac protection by a rationally designed peptide that causes ε protein kinase C translocation. PNAS. 1999;96:12798–803.PubMedCrossRef

48.

Ping P, Song C, Zhang J, et al. Formation of protein kinase Cε-Lck signaling modules confers cardioprotection. J Clin Invest. 2002;109:499–507.PubMed

49.

Gray MO, Karliner JS, Mochly-Rosen D. A selective ε-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death. J Biol Chem. 1997;272:30945–51.PubMedCrossRef

50.

Liu GS, Cohen MV, Mochly-Rosen D, Downey JM. Protein kinase C-ε is responsible for the protection of preconditioning in rabbit cardiomyocytes. J Mol Cell Cardiol. 1999;31:1937–48.PubMedCrossRef

51.

Chen L, Hahn H, Wu G, et al. Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and εPKC. Proc Natl Acad Sci. 2001;98:11114–9.PubMedCrossRef

52.

Inagaki K, Begley R, Ikeno F, Mochly-Rosen D. Cardioprotection by ε-protein kinase C activation from ischemia: continuous delivery and antiarrhythmic effect of an ε-protein kinase C-activating peptide. Circulation. 2005;111:44–50.PubMedCrossRef

53.

Saurin AT, Pennington DJ, Raat NJH, et al. Targeted disruption of the protein kinase C epsilon gene abolishes the infarct size reduction that follows ischaemic preconditioning of isolated buffer-perfused mouse hearts. Cardiovasc Res. 2002;55:672–80.PubMedCrossRef

54.

Hahn HS, Yussman MG, Toyokawa T, et al. Ischemic protection and myofibrillar cardiomyopathy: dose-dependent effects of in vivo δPKC inhibition. Circ Res. 2002;91:741–8.PubMedCrossRef

55.

Inagaki K, Hahn HS, Dorn GW 2nd, Mochly-Rosen D. Additive protection of the ischemic heart ex vivo by combined treatment with δ-protein kinase C inhibitor and ε-protein kinase C activator. Circulation. 2003;108:869–75.PubMedCrossRef

56.

Kawamura S, Yoshida K-i, Miura T, et al. Ischemic preconditioning translocates PKC-δ and -ε, which mediate functional protection in isolated rat heart. Am J Physiol. 1998;275:H2266–71.PubMed

57.

Zhao J, Renner O, Wightman L, et al. The expression of constitutively active isotypes of protein kinase C to investigate preconditioning. J Biol Chem. 1998;273:23072–9.PubMedCrossRef

58.

Mayr M, Metzler B, Chung Y-L, et al. Ischemic preconditioning exaggerates cardiac damage in PKC-δ null mice. Am J Physiol. 2004;287:H946–56.

59.

Inagaki K, Chen L, Ikeno F, et al. Inhibition of δ-protein kinase C protects against reperfusion injury of the ischemic heart in vivo. Circulation. 2003;108:2304–7.PubMedCrossRef

60.

Inagaki K, Churchill E, Mochly-Rosen D. Epsilon protein kinase C as a potential therapeutic target for the ischemic heart. Cardiovasc Res. 2006;70:222–30.PubMedCrossRef

61.

Murphy E. Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection. Circ Res. 2004;94:7–16.PubMedCrossRef

62.

Kuno A, Critz SD, Cui L, et al. Protein kinase C protects preconditioned rabbit hearts by increasing sensitivity of adenosine A_2b-dependent signaling during early reperfusion. J Mol Cell Cardiol. 2007;43:262–71.PubMedCrossRef

63.

Kitakaze M, Hori M, Takashima S, et al. Ischemic preconditioning increases adenosine release and 5′- nucleotidase activity during myocardial ischemia and reperfusion in dogs: implications for myocardial salvage. Circulation. 1993;87:208–15.PubMed

64.

Kitakaze M, Hori M, Morioka T, et al. α₁-Adrenoceptor activation increases ecto-5′-nucleotidase activity and adenosine release in rat cardiomyocytes by activating protein kinase C. Circulation. 1995;91:2226–34.PubMed

65.

Eckle T, Krahn T, Grenz A, et al. Cardioprotection by ecto-5′-nucleotidase (CD73) and A_2B adenosine receptors. Circulation. 2007;115:1581–90.PubMedCrossRef

66.

Eckle T, Köhler D, Lehmann R, et al. Hypoxia-inducible factor-1 is central to cardioprotection: a new paradigm for ischemic preconditioning. Circulation. 2008;118:166–75.PubMedCrossRef

67.

Schulz R, Post H, Vahlhaus C, Heusch G. Ischemic preconditioning in pigs: a graded phenomenon. Its relation to adenosine and bradykinin. Circulation. 1998;98:1022–9.PubMed

68.

Goto M, Cohen MV, Van Wylen DGL, Downey JM. Attenuated purine production during subsequent ischemia in preconditioned rabbit myocardium is unrelated to the mechanism of protection. J Mol Cell Cardiol. 1996;28:447–54.PubMedCrossRef

69.

Harrison GJ, Willis RJ, Headrick JP. Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart. Cardiovasc Res. 1998;40:74–87.PubMedCrossRef

70.

Philipp S, Yang X-M, Cui L, et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A_2b receptor cascade. Cardiovasc Res. 2006;70:308–14.PubMedCrossRef

71.

Hausenloy DJ, Tsang A, Mocanu MM, Yellon DM. Ischemic preconditioning protects by activating prosurvival kinases at reperfusion. Am J Physiol. 2005;288:H971–6.

72.

Baines CP, Wang L, Cohen MV, Downey JM. Myocardial protection by insulin is dependent on phosphatidylinositol 3-kinase but not protein kinase C or K_ATP channels in the isolated rabbit heart. Basic Res Cardiol. 1999;94:188–98.PubMedCrossRef

73.

Xu Z, Yang X-M, Cohen MV, et al. Limitation of infarct size in rabbit hearts by the novel adenosine receptor agonist AMP 579 administered at reperfusion. J Mol Cell Cardiol. 2000;32:2339–47.PubMedCrossRef

74.

Albrecht B, Krahn T, Philipp S, et al. Selective adenosine A_2b receptor activation mimics postconditioning in a rabbit infarct model. Circulation. 2006;114(Suppl II):II-14–5.

75.

Baxter GF, Mocanu MM, Brar BK, et al. Cardioprotective effects of transforming growth factor-β1 during early reoxygenation or reperfusion are mediated by p42/p44 MAPK. J Cardiovasc Pharmacol. 2001;38:930–9.PubMedCrossRef

76.

Schulman D, Latchman DS, Yellon DM. Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway. Am J Physiol. 2002;283:H1481–8.

77.

Liao Z, Brar BK, Cai Q, et al. Cardiotrophin-1 (CT-1) can protect the adult heart from injury when added both prior to ischaemia and at reperfusion. Cardiovasc Res. 2002;53:902–10.PubMedCrossRef

78.

Yang X-M, Krieg T, Cui L, et al. NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO. J Mol Cell Cardiol. 2004;36:411–21.PubMedCrossRef

79.

Yang X-M, Philipp S, Downey JM, Cohen MV. Atrial natriuretic peptide administered just prior to reperfusion limits infarction in rabbit hearts. Basic Res Cardiol. 2006;101:311–8.PubMedCrossRef

80.

Cai Z, Semenza GL. Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury. Circulation. 2004;109:2050–3.PubMedCrossRef

81.

Parsa CJ, Kim J, Riel RU, et al. Cardioprotective effects of erythropoietin in the reperfused ischemic heart: a potential role for cardiac fibroblasts. J Biol Chem. 2004;279:20655–62.PubMedCrossRef

82.

Hausenloy DJ, Ong S-B, Yellon DM. The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res Cardiol. 2009;104:189–202.PubMedCrossRef

83.

Kitakaze M, Asakura M, Kim J, et al. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet. 2007;370:1483–93.PubMedCrossRef

84.

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

85.

Hunter DR, Haworth RA, Southard JH. Relationship between configuration, function, and permeability in calcium-treated mitochondria. J Biol Chem. 1976;251:5069–77.PubMed

86.

Crompton M, Costi A. Kinetic evidence for a heart mitochondrial pore activated by Ca²⁺, inorganic phosphate and oxidative stress. A potential mechanism for mitochondrial dysfunction during cellular Ca²⁺ overload. Eur J Biochem. 1988;178:489–501.PubMedCrossRef

87.

Crompton M, Ellinger H, Costi A. Inhibition by cyclosporin A of a Ca²⁺-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J. 1988;255:357–60.PubMed

88.

Nazareth W, Yafei N, Crompton M. Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A. J Mol Cell Cardiol. 1991;23:1351–4.PubMedCrossRef

89.

Griffiths EJ, Halestrap AP. Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol. 1993;25:1461–9.PubMedCrossRef

90.

Griffiths EJ, Halestrap AP. Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J. 1995;307:93–8.PubMed

91.

Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM. Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res. 2002;55:534–43.PubMedCrossRef

92.

Baines CP. The mitochondrial permeability transition pore and ischemia-reperfusion injury. Basic Res Cardiol. 2009;104:181–8.PubMedCrossRef

93.

Baines CP. The molecular composition of the mitochondrial permeability transition pore. J Mol Cell Cardiol. 2009;46:850–7.PubMedCrossRef

94.

Tong H, Imahashi K, Steenbergen C, Murphy E. Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective. Circ Res. 2002;90:377–9.PubMedCrossRef

95.

Gross ER, Hsu AK, Gross GJ. Opioid-induced cardioprotection occurs via glycogen synthase kinase β inhibition during reperfusion in intact rat hearts. Circ Res. 2004;94:960–6.PubMedCrossRef

96.

Nishihara M, Miura T, Miki T, et al. Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3β. Am J Physiol. 2006;291:H748–55.

97.

Korzick DH, Kostyak JC, Hunter JC, Saupe KW. Local delivery of PKCε-activating peptide mimics ischemic preconditioning in aged hearts through GSK-3β but not F₁-ATPase inactivation. Am J Physiol. 2007;293:H2056–63.

98.

Das S, Wong R, Rajapakse N, et al. Glycogen synthase kinase 3 inhibition slows mitochondrial adenine nucleotide transport and regulates voltage-dependent anion channel phosphorylation. Circ Res. 2008;103:983–91.PubMedCrossRef

99.

Obame FN, Plin-Mercier C, Assaly R, et al. Cardioprotective effect of morphine and a blocker of glycogen synthase kinase 3β, SB216763 [3-(2, 4-dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2, 5-dione], via inhibition of the mitochondrial permeability transition pore. J Pharmacol Exp Ther. 2008;326:252–8.PubMedCrossRef

100.

Juhaszova M, Zorov DB, Kim S-H, et al. Glycogen synthase kinase-3β mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest. 2004;113:1535–49.PubMed

101.

Garlid KD, Costa ADT, Quinlan CL, et al. Cardioprotective signaling to mitochondria. J Mol Cell Cardiol. 2009;46:858–66.PubMedCrossRef

102.

Gross ER, Hsu AK, Gross GJ. GSK3β inhibition and K_ATP channel opening mediate acute opioid-induced cardioprotection at reperfusion. Basic Res Cardiol. 2007;102:341–9.PubMedCrossRef

103.

Nishino Y, Webb IG, Davidson SM, et al. Glycogen synthase kinase-3 inactivation is not required for ischemic preconditioning or postconditioning in the mouse. Circ Res. 2008;103:307–14.PubMedCrossRef

104.

Skyschally A, van Caster P, Boengler K, et al. Ischemic postconditioning in pigs: no causal role for RISK activation. Circ Res. 2009;104:15–8.PubMedCrossRef

105.

Xi J, McIntosh R, Shen X, et al. Adenosine A_2A and A_2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts. J Mol Cell Cardiol. 2009;47:684–90.PubMedCrossRef

106.

Vinten-Johansen J, Thourani VH, Ronson RS, et al. Broad-spectrum cardioprotection with adenosine. Ann Thorac Surg. 1999;68:1942–8.PubMedCrossRef

107.

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

108.

Gomez L, Li B, Mewton N, et al. Inhibition of mitochondrial permeability transition pore opening: translation to patients. Cardiovasc Res. 2009;83:226–33.PubMedCrossRef

Title: Mechanism of Cardioprotection by Early Ischemic Preconditioning
Authors: Xiulan Yang
Michael V. Cohen
James M. Downey
Publication date: 01-06-2010
Publisher: Springer US
Published in: Cardiovascular Drugs and Therapy / Issue 3/2010
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-010-6236-x

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mechanism of Cardioprotection by Early Ischemic Preconditioning

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2010

Postconditioning in Reperfusion Injury: A Status Report

Cardioprotection in the Clinical Setting

Cardioprotection in the Clinical Setting-Lessons from J-WIND Studies

How to Mediate Cardioprotection in Ischemic Hearts—Accumulated Evidence of Basic Research Should Translate to Clinical Medicine

Mitochondria and GSK-3β in Cardioprotection Against Ischemia/Reperfusion Injury

Role of Dual Antiplatelet Therapy in Symptomatic Patients with Established Vascular Disease: Putting the CHARISMA Trial into Therapeutic Perspective

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page