Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase

Huang,Yi-E; Tang,Zhi-Han; Xie,Wei; Shen,Xin-Tian; Liu,Mi-Hua; Peng,Xiang-Ping; Zhao,Zhan-Zhi; Nie,De-Bo; Liu,Lu-Shan; Jiang,Zhi-Sheng

doi:10.3892/etm.2012.733

Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase

Authors:
- Yi-E Huang
- Zhi-Han Tang
- Wei Xie
- Xin-Tian Shen
- Mi-Hua Liu
- Xiang-Ping Peng
- Zhan-Zhi Zhao
- De-Bo Nie
- Lu-Shan Liu
- Zhi-Sheng Jiang
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Affiliations: Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, P.R. China, Huaihua Medical College, Huaihua, Hunan 418000, P.R. China
Published online on: October 1, 2012 https://doi.org/10.3892/etm.2012.733
Pages: 1117-1123

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Abstract

Hydrogen sulﬁde (H2S), produced by cystanthionine-γ-lysase (CSE) in the cardiovascular system, has been suggested to be the third gasotransmitter in addition to nitric oxide (NO) and carbon monoxide (CO). The present study aimed to investigate the role of H2S in ischemic postconditioning (IPO) during the early period of reperfusion. IPO with 6 episodes of 10 sec reperfusion followed by 6 episodes of 10 sec ischemia (IPO 2') was administered when reperfusion was initiated. Cardiodynamics and the concentration of H2S were measured at 1, 2, 3, 4, 5, 10, 20, 30, 60, 90 and 120 min of reperfusion. Lactate dehydrogenase (LDH) levels and infarct size were determined at the end of the reperfusion. The concentration of H2S was stable during the whole experiment in the control group, whereas it reached a peak at the first minute of reperfusion in the ischemia-reperfusion (IR) group. The concentration of H2S at the first minute of reperfusion in the IPO 2' group was higher compared to that of the IR group, which correlated with cardioprotection including improved heart contractile function and reduced infarct size and LDH levels. However, the above effects of IPO 2' were attenuated by pre-treatment with blockade of endogenous H2S production with DL-propargylglycine for 20 min prior to global ischemia. Furthermore, we found that other forms of IPO, IPO commencing at 1 min after reperfusion (delayed IPO) or lasting only for 1 min (IPO 1'), failed to increase the concentration of H2S and protect the myocardium. We conclude that the peak of endogenous H2S in the early reperfusion phase is the key to cardioprotection induced by IPO.

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1	Na HS, Kim YI, Yoon YW, Han HC, Nahm SH and Hong SK: 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. 132:78–83. 1996. View Article : Google Scholar
2	Zhao ZQ, Corvera JS, Halkos ME, et al: Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol. 285:H579–588. 2003. View Article : Google Scholar : PubMed/NCBI
3	Kin H, Zhao ZQ, Sun HY, et al: Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion. Cardiovasc Res. 62:74–85. 2004. View Article : Google Scholar : PubMed/NCBI
4	Cohen MV, Yang XM and Downey JM: The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation. 115:1895–1903. 2007. View Article : Google Scholar : PubMed/NCBI
5	Hausenloy DJ, Duchen MR and Yellon DM: Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res. 60:617–625. 2003. View Article : Google Scholar
6	Sun HY, Wang NP, Kerendi F, et al: Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca²⁺ overload. Am J Physiol Heart Circ Physiol. 288:H1900–1908. 2005. View Article : Google Scholar : PubMed/NCBI
7	Wang R: Two’s company, three’s a crowd: can H₂S be the third endogenous gaseous transmitter? Faseb J. 16:1792–1798. 2002.
8	Szabo C: Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov. 6:917–935. 2007. View Article : Google Scholar : PubMed/NCBI
9	Geng B, Yang J, Qi Y, et al: H₂S generated by heart in rat and its effects on cardiac function. Biochem Biophys Res Commun. 313:362–368. 2004.
10	Zhao W, Zhang J, Lu Y and Wang R: The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. Embo J. 20:6008–6016. 2001. View Article : Google Scholar : PubMed/NCBI
11	Yong QC, Pan TT, Hu LF and Bian JS: Negative regulation of beta-adrenergic function by hydrogen sulphide in the rat hearts. J Mol Cell Cardiol. 44:701–710. 2008. View Article : Google Scholar : PubMed/NCBI
12	Geng B, Chang L, Pan C, et al: Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun. 318:756–763. 2004. View Article : Google Scholar : PubMed/NCBI
13	Elrod JW, Calvert JW, Morrison J, et al: Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA. 104:15560–15565. 2007. View Article : Google Scholar : PubMed/NCBI
14	Johansen D, Ytrehus K and Baxter GF: Exogenous hydrogen sulfide (H₂S) protects against regional myocardial ischemiareperfusion injury - evidence for a role of K ATP channels. Basic Res Cardiol. 101:53–60. 2006.
15	Sivarajah A, McDonald MC and Thiemermann C: The production of hydrogen sulfide limits myocardial ischemia and reperfusion injury and contributes to the cardioprotective effects of preconditioning with endotoxin, but not ischemia in the rat. Shock. 26:154–161. 2006. View Article : Google Scholar : PubMed/NCBI
16	Zhu YZ, Wang ZJ, Ho P, et al: Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats. J Appl Physiol. 102:261–268. 2007. View Article : Google Scholar : PubMed/NCBI
17	Yong QC, Lee SW, Foo CS, Neo KL, Chen X and Bian JS: Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning. Am J Physiol Heart Circ Physiol. 295:H1330–H1340. 2008. View Article : Google Scholar : PubMed/NCBI
18	Morrison RR, Talukder MA, Ledent C and Mustafa SJ: Cardiac effects of adenosine in A(2A) receptor knockout hearts: uncovering A(2B) receptors. Am J Physiol Heart Circ Physiol. 282:H437–H444. 2002. View Article : Google Scholar : PubMed/NCBI
19	Bian JS, Yong QC, Pan TT, et al: Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes. J Pharmacol Exp Ther. 316:670–678. 2006. View Article : Google Scholar : PubMed/NCBI
20	Zhu YZ, Chong CL, Chuah SC, et al: Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats. Am J Physiol Heart Circ Physiol. 290:H517–H524. 2006. View Article : Google Scholar : PubMed/NCBI
21	Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J and Przyklenk K: Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol. 289:H1618–1626. 2005. View Article : Google Scholar : PubMed/NCBI
22	Yang XM, Philipp S, Downey JM and 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. 100:57–63. 2005.
23	Crisostomo PR, Wang M, Wairiuko GM, Terrell AM and Meldrum DR: Postconditioning in females depends on injury severity. J Surg Res. 134:342–347. 2006. View Article : Google Scholar : PubMed/NCBI
24	Fantinelli JC and Mosca SM: Comparative effects of ischemic pre and postconditioning on ischemia-reperfusion injury in spontaneously hypertensive rats (SHR). Mol Cell Biochem. 296:45–51. 2007. View Article : Google Scholar : PubMed/NCBI
25	Kin H, Zatta AJ, Lofye MT, et al: Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res. 67:124–133. 2005. View Article : Google Scholar : PubMed/NCBI
26	Zhu M, Feng J, Lucchinetti E, et al: Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway. Cardiovasc Res. 72:152–162. 2006. View Article : Google Scholar : PubMed/NCBI
27	Wang HC, Zhang HF, Guo WY, et al: Hypoxic postconditioning enhances the survival and inhibits apoptosis of cardiomyocytes following reoxygenation: role of peroxynitrite formation. Apoptosis. 11:1453–1460. 2006. View Article : Google Scholar
28	Dombkowski RA, Russell MJ and Olson KR: Hydrogen sulfide as an endogenous regulator of vascular smooth muscle tone in trout. Am J Physiol Regul Integr Comp Physiol. 286:R678–R685. 2004. View Article : Google Scholar : PubMed/NCBI
29	Penna C, Mancardi D, Rastaldo R, Losano G and Pagliaro P: Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling. Cardiovasc Res. 75:168–177. 2007. View Article : Google Scholar
30	Weihrauch D, Krolikowski JG, Bienengraeber M, Kersten JR, Warltier DC and Pagel PS: Morphine enhances isoflurane-induced postconditioning against myocardial infarction: the role of phosphatidylinositol-3-kinase and opioid receptors in rabbits. Anesth Analg. 101:942–949. 2005. View Article : Google Scholar
31	Whiteman M, Armstrong JS, Chu SH, et al: The novel neuro-modulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’? J Neurochem. 90:765–768. 2004.PubMed/NCBI
32	Whiteman M, Cheung NS, Zhu YZ, et al: Hydrogen sulphide: a novel inhibitor of hypochlorous acid-mediated oxidative damage in the brain? Biochem Biophys Res Commun. 326:794–798. 2005. View Article : Google Scholar : PubMed/NCBI
33	Hassouna A, Matata BM and Galinanes M: PKC-epsilon is upstream and PKC-alpha is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium. Am J Physiol Cell Physiol. 287:C1418–C1425. 2004. View Article : Google Scholar : PubMed/NCBI