Protective effect of remote ischemic pre‑conditioning on patients undergoing cardiac bypass valve replacement surgery: A randomized controlled trial

Jin,Xiuling; Wang,Liangrong; Li,Liling; Zhao,Xiyue

doi:10.3892/etm.2019.7192

Protective effect of remote ischemic pre‑conditioning on patients undergoing cardiac bypass valve replacement surgery: A randomized controlled trial

Authors:
- Xiuling Jin
- Liangrong Wang
- Liling Li
- Xiyue Zhao
View Affiliations

Affiliations: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: January 21, 2019 https://doi.org/10.3892/etm.2019.7192
Pages: 2099-2106
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Remote ischemic pre‑conditioning (RIPC) may have a protective effect on myocardial injury associated with cardiac bypass surgery (CPB). The objective of the present study was to investigate the effect of RIPC on ischemia/reperfusion (I/R) injury and to assess the underlying mechanisms. A total of 241 patients who underwent valve replacement were randomly assigned to receive either RIPC (n=121) or control group (n=120). The primary endpoint was peri‑operative myocardial injury (PMI), which was determined by serum Highly sensitive cardiac troponin T (hsTnT). The secondary endpoint was the blood gas indexes, acute lung injury and length of intensive care unit stay, length of hospital stay and major adverse cardiovascular events. The results indicated that in comparison with control group, RIPC treatment reduced the levels of hsTnT at 6 and 24 h post‑CPB (P<0.001), as well as the alveolar‑arterial oxygen pressure difference and respiratory index after CPB. Furthermore, RIPC reduced the incidence of acute lung injury by 15.3% (54.1% in the control group vs. 41.3% in the RIPC group, P=0.053). It was indicated that RIPC provided myocardial and pulmonary protection during CPB. In addition, the length of the intensive care unit and hospital stay was reduced by RIPC. Mechanistic investigation revealed a reduced content of soluble intercellular adhesion molecule‑1, endothelin‑1 and malondialdehyde, as well as elevated levels of nitric oxide in the RIPC group compared with those in the control group. This indicated that RIPC protected against I/R injury associated with CPB through reducing the inflammatory response and oxidative damage, as well as improving pulmonary vascular tension. In conclusion, RIPC reduced myocardial and pulmonary injury associated with CPB. This protective effect may be associated with the inhibition of the inflammatory response and oxidative injury. The present study proved the efficiency of this approach in reducing ischemia/reperfusion injury associated with cardiac surgery. Clinical trial registry no. ChiCTR1800015393.

View Figures

View References

1	Ignarro LJ, Buga GM, Wood KS, Byrns RE and Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA. 84:9265–9269. 1987. View Article : Google Scholar : PubMed/NCBI
2	Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K and Masaki T: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 332:411–415. 1988. View Article : Google Scholar : PubMed/NCBI
3	Jalowy A, Schulz R and Heusch G: AT1 receptor blockade in experimental myocardial ischemia/reperfusion. J Am Soc Nephrol. 10 Suppl 11:S129–S136. 1999.PubMed/NCBI
4	Kubota I, Han X, Opel DJ, Zhao YY, Baliga R, Huang P, Fishman MC, Shannon RP, Michel T and Kelly RA: Increased susceptibility to development of triggered activity in myocytes from mice with targeted disruption of endothelial nitric oxide synthase. J Mol Cell Cardiol. 32:1239–1248. 2000. View Article : Google Scholar : PubMed/NCBI
5	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. 33:1897–1918. 2001. View Article : Google Scholar : PubMed/NCBI
6	Yang XM, Proctor JB, Cui L, Krieg T, Downey JM and Cohen MV: Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol. 44:1103–1110. 2004. View Article : Google Scholar : PubMed/NCBI
7	Liu X, Chen H, Zhan B, Xing B, Zhou J, Zhu H and Chen Z: Attenuation of reperfusion injury by renal ischemic postconditioning: The role of NO. Biochem Biophys Res Commun. 359:628–634. 2007. View Article : Google Scholar : PubMed/NCBI
8	Hasdai D, Kornowski R and Battler A: Endothelin and myocardial ischemia. Cardiovasc Drugs Ther. 8:589–599. 1994. View Article : Google Scholar : PubMed/NCBI
9	Lang SC, Elsässer A, Scheler C, Vetter S, Tiefenbacher CP, Kübler W, Katus HA and Vogt AM: Myocardial preconditioning and remote renal preconditioning-identifying a protective factor using proteomic methods? Basic Res Cardiol. 101:149–158. 2006. View Article : Google Scholar : PubMed/NCBI
10	Zhou W, Zeng D, Chen R, Liu J, Yang G, Liu P and Zhou X: Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants. Pediatr Cardiol. 31:22–29. 2010. View Article : Google Scholar : PubMed/NCBI
11	Tuttolomondo A, Pecoraro R, Casuccio A, Di Raimondo D, Buttà C, Clemente G, Della Corte V, Guggino G, Arnao V, Maida C, et al: Peripheral frequency of CD4+ CD28- cells in acute ischemic stroke: Relationship with stroke subtype and severity markers. Medicine (Baltimore). 94:e8132015. View Article : Google Scholar : PubMed/NCBI
12	Tuttolomondo A, Pedone C, Pinto A, Di Raimondo D, Fernandez P, Di Sciacca R and Licata G; Gruppo Italiano di Farmacoepidemiologia dell'Anziano (GIFA) researchers, : Predictors of outcome in acute ischemic cerebrovascular syndromes: The GIFA study. Int J Cardiol. 125:391–396. 2008. View Article : Google Scholar : PubMed/NCBI
13	Di Raimondo D, Tuttolomondo A, Buttà C, Miceli S, Licata G and Pinto A: Effects of ACE-inhibitors and angiotensin receptor blockers on inflammation. Curr Pharm Des. 18:4385–4413. 2012. View Article : Google Scholar : PubMed/NCBI
14	Przepiera-Będzak H, Fischer K and Brzosko M: Serum interleukin-18, Fetuin-A, soluble intercellular adhesion molecule-1, and endothelin-1 in ankylosing spondylitis, psoriatic arthritis and SAPHO syndrome. Int J Mol Sci. 17(pii): E12552016. View Article : Google Scholar : PubMed/NCBI
15	Dröge W: Free radicals in the physiological control of cell function. Physiol Rev. 82:47–95. 2002. View Article : Google Scholar : PubMed/NCBI
16	Lønborg J, Kelbaek H, Vejlstrup N, Jørgensen E, Helqvist S, Saunamäki K, Clemmensen P, Holmvang L, Treiman M, Jensen JS and Engstrøm T: Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance. Circ Cardiovasc Interv. 3:34–41. 2010. View Article : Google Scholar : PubMed/NCBI
17	Hashmi MA, Ahsan B, Shah SIA and Khan MIU: Antioxidant capacity and lipid peroxidation product in pulmonary tuberculosis. Al Ame en J Med Sci. 5:313–319. 2012.
18	Muehlschlegel JD, Perry TE, Liu KY, Nascimben L, Fox AA, Collard CD, Avery EG, Aranki SF, D'Ambra MN, Shernan SK, et al: Troponin is superior to electrocardiogram and creatinine kinase MB for predicting clinically significant myocardial injury after coronary artery bypass grafting. Eur Heart J. 30:1574–1583. 2009. View Article : Google Scholar : PubMed/NCBI
19	Erdil N, Eroglu T, Akca B, Disli OM, Yetkin O, Colak MC, Erdil F and Battaloglu B: The effects of N-acetylcysteine on pulmonary functions in patients undergoing on-pump coronary artery surgery: A double blind placebo controlled study. Eur Rev Med Pharmacol Sci. 20:180–187. 2016.PubMed/NCBI
20	Bonservizi WG, Koike MK, Saurim R, Felix GA, da Silva SM, Montero EF and Taha MO: Ischemic preconditioning and atenolol on lung injury after intestinal ischemia and reperfusion in rats. Transplant Proc. 46:1862–1866. 2014. View Article : Google Scholar : PubMed/NCBI
21	Przyklenk K, Bauer B, Ovize M, Kloner RA and Whittaker P: Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 87:893–899. 1993. View Article : Google Scholar : PubMed/NCBI
22	Hausenloy DJ and Yellon DM: Remote ischaemic preconditioning: Underlying mechanisms and clinical application. Cardiovasc Res. 79:377–386. 2008. View Article : Google Scholar : PubMed/NCBI
23	Sivaraman V, Pickard JM and Hausenloy DJ: Remote ischaemic conditioning: Cardiac protection from afar. Anaesthesia. 70:732–748. 2015. View Article : Google Scholar : PubMed/NCBI
24	Heusch G, Bøtker HE, Przyklenk K, Redington A and Yellon D: Remote ischemic conditioning. J Am Coll Cardiol. 65:177–195. 2015. View Article : Google Scholar : PubMed/NCBI
25	Young PJ, Dalley P, Garden A, Horrocks C, La Flamme A, Mahon B, Miller J, Pilcher J, Weatherall M, Williams J, et al: A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol. Basic Res Cardiol. 107:2562012. View Article : Google Scholar : PubMed/NCBI
26	Rahman IA, Mascaro JG, Steeds RP, Frenneaux MP, Nightingale P, Gosling P, Townsend P, Townend JN, Green D and Bonser RS: Remote ischemic preconditioning in human coronary artery bypass surgery: From promise to disappointment? Circulation. 122:9266672010. View Article : Google Scholar
27	Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J and Yellon DM: Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: A randomised controlled trial. Heart. 95:1567–1571. 2009. View Article : Google Scholar : PubMed/NCBI
28	Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, et al: Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: A randomised controlled trial. Lancet. 370:575–579. 2007. View Article : Google Scholar : PubMed/NCBI
29	Ali N, Rizwi F, Iqbal A and Rashid A: Induced remote ischemic pre-conditioning on ischemia-reperfusion injury in patients undergoing coronary artery bypass. J Coll Physicians Surg Pak. 20:427–431. 2010.PubMed/NCBI
30	Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H and Heusch G: Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 105:657–664. 2010. View Article : Google Scholar : PubMed/NCBI
31	Hoole SP, Heck PM, Sharples L, Khan SN, Duehmke R, Densem CG, Clarke SC, Shapiro LM, Schofield PM, O'Sullivan M and Dutka DP: Cardiac remote ischemic preconditioning in coronary stenting (CRISP Stent) study: A prospective, randomized control trial. Circulation. 119:820–827. 2009. View Article : Google Scholar : PubMed/NCBI
32	Candilio L, Malik A, Ariti C, Barnard M, Di Salvo C, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, et al: Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: A randomised controlled clinical trial. Heart. 101:185–192. 2015. View Article : Google Scholar : PubMed/NCBI
33	Lopez-Calle E, Espindola P, Spinke J, Lutz S, Nichtl A, Tgetgel A, Herbert N, Marcinowski M, Klepp J, Fischer T, et al: A new immunochemistry platform for a guideline-compliant cardiac troponin T assay at the point of care: proof of principle. Clin Chem Lab Med. 55:1798–1804. 2017. View Article : Google Scholar : PubMed/NCBI
34	Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A and Spragg R: The American-European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes and clinical trial coordination. Am J Respir Crit Care Med. 149:818–824. 1994. View Article : Google Scholar : PubMed/NCBI
35	Zhang C, Gong W, Liu H, Guo Z and Ge S: Inhibition of matrix metalloproteinase-9 with low-dose doxycycline reduces acute lung injury induced by cardiopulmonary bypass. Int J Clin Exp Med. 7:4975–4982. 2014.PubMed/NCBI
36	Pilcher JM, Young P, Weatherall M, Rahman I, Bonser RS and Beasley RW: A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery. J R Soc Med. 105:436–445. 2012. View Article : Google Scholar : PubMed/NCBI
37	Karuppasamy P, Chaubey S, Dew T, Musto R, Sherwood R, Desai J, John L, Shah AM, Marber MS and Kunst G: Remote intermittent ischemia before coronary artery bypass graft surgery: A strategy to reduce injury and inflammation? Basic Res Cardiol. 106:511–519. 2011. View Article : Google Scholar : PubMed/NCBI
38	Adabag AS, Wassif HS, Rice K, Mithani S, Johnson D, Bonawitz-Conlin J, Ward HB, McFalls EO, Kuskowski MA and Kelly RF: Preoperative pulmonary function and mortality after cardiac surgery. Am Heart J. 159:691–697. 2010. View Article : Google Scholar : PubMed/NCBI
39	Mazzeffi M, Kassa W, Gammie J, Tanaka K, Roman P, Zhan M, Griffith B and Rock P: Preoperative aspirin use and lung injury after aortic valve replacement surgery: A retrospective cohort study. Anesth Analg. 121:271–277. 2015. View Article : Google Scholar : PubMed/NCBI
40	Zimmerman RF, Ezeanuna PU, Kane JC, Cleland CD, Kempananjappa TJ, Lucas FL and Kramer RS: Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery. Kidney Int. 80:861–867. 2011. View Article : Google Scholar : PubMed/NCBI
41	Karu I, Tahepold P, Ruusalepp A, Reimann E, Koks S and Starkopf J: Exposure to sixty min of hyperoxia upregulates myocardial humanins in patients with coronary artery disease-a pilot study. J Physiol Pharmacol. 66:899–906. 2015.PubMed/NCBI
42	Pinheiro DF, Fontes B, Shimazaki JK, Heimbecker AM, Jacysyn Jde F, Rasslan S, Montero EF and Utiyama EM: Ischemic preconditioning modifies mortality and inflammatory response. Acta Cir Bras. 31:1–7. 2016. View Article : Google Scholar : PubMed/NCBI
43	Ucar G, Topaloglu E, Kandilci HB and Gümüsel B: Effect of ischemic preconditioning on reactive oxygen species-mediated ischemia-reperfusion injury in the isolated perfused rat lung. Clin Biochem. 38:681–684. 2005. View Article : Google Scholar : PubMed/NCBI
44	Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YH, Wang H, et al: Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 133:235–249. 2008. View Article : Google Scholar : PubMed/NCBI
45	Victorino GP, Wisner DH and Tucker VL: Basal release of nitric oxide and its interaction with endothelin-1 on single vessel hydraulic permeability. J Trauma. 50:535–539. 2001. View Article : Google Scholar : PubMed/NCBI