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Pulmonary reperfusion injury


1Department of Cardiothoracic Surgery, The First Hospital of Putian, Teaching Hospital, Fujian Medical University, Putian 351100, Fujian Province, People’s Republic of China

DOI: 10.22514/SV131.052017.30 Vol.13,Issue 1,March 2017 pp.14-18

Published: 20 March 2017

*Corresponding Author(s): SHI-MIN YUAN E-mail:


Pulmonary reperfusion injury is a clinical syndrome with no single and recognized pathophysiologic mechanism. It is a ma-jor cause of morbidity and mortality fol-lowing lung transplantation, cardiogenic shock, or cardiopulmonary bypass. The underlying mechanisms remain uncertain. Lung inflammatory injury induced by li-popolysaccharide, characterized by rapid sequestration of neutrophils in response to inflammatory chemokines and cytokines released in the lungs is an acceptable the-ory. Structural or functional impairment of surfactant has been noted in pulmo-nary reperfusion injury. The pathological changes may include bilateral pulmonary infiltrates, reduced lung compliance and worsening of gas exchange in the imme-diate posttransplant period. Recruitment maneuver and high positive end-expir-atory pressure can relieve postoperative respiratory failure, especially in the pa-tient with reperfusion pulmonary edema after pulmonary thromboendarterectomy. Pharmaceutical agents, including inhaled nitric oxide, soluble complement receptor type 1, prostaglandin E1 and exogenous surfactant, attenuate pulmonary reperfu-sion injury through distinct mechanisms. Extracorporeal membrane oxygenation and Novalung are temporary assistance in bridging to lung transplantation, stabiliza-tion of hemodynamics during transplanta-tion and treatment of severe lung dysfunc-tion and primary graft failure. Modulation of heme oxygenase-1 expression, ischemic conditioning and gene therapy are future directions for pulmonary reperfusion in-jury management.


cardiopulmonary bypass, pul-monary hypertension, respiratory insuffi-ciency

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SHI-MIN YUAN. Pulmonary reperfusion injury. Signa Vitae. 2017. 13(1);14-18.


1. Sakuma T, Takahashi K, Ohya N, Kajikawa O, Martin TR, Albertine KH, et al. Ischemia-reperfusion lung injury in rabbits: mecha-nisms of injury and protection. Am J Physiol 1999;276(1 Pt 1):L137-45.

2. Fischer S, Maclean AA, Liu M, Cardella JA, Slutsky AS, Suga M, et al. Dynamic changes in apoptotic and necrotic cell death correlate with severity of ischemia-reperfusion injury in lung transplantation. Am J Respir Crit Care Med 2000;162(5):1932-9.

3. Okada Y, Kondo T. Preservation solution for lung transplantation. Gen Thorac Cardiovasc Surg 2009;57(12):635-9.

4. Fadel E, Mazmanian GM, Chapelier A, Baudet B, Detruit H, de Montpreville V, et al. Lung reperfusion injury after chronic or acute unilateral pulmonary artery occlusion. Am J Respir Crit Care Med 1998;157(4 Pt 1):1294-300.

5. de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 2003;167(4):490-511.

6. Ng CS, Wan S, Yim AP, Arifi AA. Pulmonary dysfunction after cardiac surgery. Chest 2002;121(4):1269-77.

7. den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol 2010;299(5):H1283-99.

8. Matot I, Einav S, Weiniger CF, Pearl RG, Abramovitch R, Joshi BV, et al. Lung injury after in vivo reperfusion: outcome at 27 hours after reperfusion. Anesthesiology 2008;109(2):269-78.

9. Della Rocca G, Pierconti F, Costa MG, Coccia C, Pompei L, Rocco M, et al. Severe reperfusion lung injury after double lung trans-plantation. Crit Care 2002;6(3):240-4.

10. Chen W, Zheng G, Yang S, Ping W, Fu X, Zhang N, et al. CYP2J2 and EETs protect against oxidative stress and apoptosis in vivo and in vitro following lung ischemia/reperfusion. Cell Physiol Biochem 2014;33(6):1663-80.

11. Ross SD, Kron IL, Gangemi JJ, Shockey KS, Stoler M, Kern JA, et al. Attenuation of lung reperfusion injury after transplantation using an inhibitor of nuclear factor-κB. Am J Physiol Lung Cell Mol Physiol 2000;279(3):L528-36.

12. Fischer S, Cassivi SD, Xavier AM, Cardella JA, Cutz E, Edwards V, et al. Cell death in human lung transplantation: apoptosis induc-tion in human lungs during ischemia and after transplantation. Ann Surg 2000;231(3):424-31.

13. Stammberger U, Gaspert A, Hillinger S, Vogt P, Odermatt B, Weder W, et al. Apoptosis induced by ischemia and reperfusion in ex-perimental lung transplantation. Ann Thorac Surg 2000;69(5):1532-6.

14. Ochs M, Nenadic I, Fehrenbach A, Albes JM, Wahlers T, Richter J, et al. Ultrastructural alterations in intraalveolar surfactant sub-types after experimental ischemia and reperfusion. Am J Respir Crit Care Med 1999;160(2):718-24.

15. Long SM, Laubach VE, Tribble CG, Kaza AK, Fiser SM, Cassada DC, et al. Pyrrolidine dithiocarbamate reduces lung reperfusion injury. J Surg Res 2003;112(1):12-8.

16. Dauber IM, Parsons PE, Welsh CH, Giclas PC, Whitman GJ, Wheeler GS, et al. Peripheral bypass-induced pulmonary and coronary vascular injury. Association with increased levels of tumor necrosis factor. Circulation 1993;88(2):726-35.

17. Jansen PG, Te Velthuis H, Oudemans-Van Straaten HM, Bulder ER, Van Deventer SJ, et al. Perfusion-related factors of endotoxin release during cardiopulmonary bypass. Eur J Cardiothorac Surg 1994;8(3):125-9.

18. Montes FR, Maldonado JD, Paez S, Ariza F. Off-pump versus on-pump coronary artery bypass surgery and postoperative pulmonary dysfunction. J Cardiothorac Vasc Anesth 2004;18(6):698-703.

19. Ranucci M, Soro G, Frigiola A, Menicanti L, Ditta A, Candido G, et al. Normothermic perfusion and lung function after cardiopul-monary bypass: effects in pulmonary risk patients. Perfusion 1997;12(5):309-15.

20. Stephens RS, Shah AS, Whitman GJ. Lung injury and acute respiratory distress syndrome after cardiac surgery. Ann Thorac Surg 2013;95(3):1122-9.

21. De Perrot M, Sekine Y, Fischer S, Waddell TK, McRae K, Liu M, et al. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am J Respir Crit Care Med 2002;165(2):211-5.

22. Yano M, Omoto Y, Yamakawa Y, Nakashima Y, Kiriyama M, Saito Y, et al. Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury. J Heart Lung Transplant 2001;20(6):679-86.

23. Delbin MA, Antunes E, Zanesco A. Role of exercise training on pulmonary ischemia/reperfusion and inflammatory response. Rev Bras Cir Cardiovasc 2009;24(4):552-61.

24. Santos CH, Aydos RD, Nogueira Neto E, Miiji LN, Cassino PC, Alves II, et al. Evaluation of pulmonary reperfusion injury in rats undergoing mesenteric ischemia and reperfusion and protective effect of postconditioning on this process. Rev Bras Cir Cardiovasc 2015;30(5):533-7.

25. Kramm T, Mayer E, Dahm M, Guth S, Menzel T, Pitton M, et al. Long-term results after thromboendarterectomy for chronic pulmo-nary embolism. Eur J Cardiothorac Surg 1999;15(5):579-83; discussion 583-4.

26. Kerr KM, Auger WR, Marsh JJ, Comito RM, Fedullo RL, Smits GJ, et al. The use of cylexin (CY-1503) in prevention of reperfusion lung injury in patients undergoing pulmonary thromboendarterectomy. Am J Respir Crit Care Med 2000;162(1):14-20.

27. Levinson RM, Shure D, Moser KM. Reperfusion pulmonary edema after pulmonary artery thromboendarterectomy. Am Rev Respir Dis 1986;134(6):1241-5.

28. Zaas D, Palmer SM. Respiratory failure early after lung transplantation: now that we know the extent of the problem, what are the solutions? Chest 2003;123(1):14-6.

29. Struber M, Hirt SW, Cremer J, Harringer W, Haverich A. Surfactant replacement in reperfusion injury after clinical lung transplanta-tion. Intensive Care Med 1999;25(8):862-4.

30. Sommer SP, Warnecke G, Hohlfeld JM, Gohrbandt B, Niedermeyer J, Kofidis T, et al. Pulmonary preservation with LPD and celsior solution in porcine lung transplantation after 24 h of cold ischemia. Eur J Cardiothorac Surg 2004;26(1):151-7.

31. Medeiros IL, Pego-Fernandes PM, Mariani AW, Fernandes FG, Unterpertinger FV, Canzian M, et al. Comparison of lung preserva-tion solutions in human lungs using an ex vivo lung perfusion experimental model. Clinics (Sao Paulo) 2012;67(9):1101-6.

32. Hausen B, Beuke M, Schroeder F, Poets CF, Hewitt C, DelRossi AJ, et al. In vivo measurement of lung preservation solution efficacy: comparison of LPD, UW, EC and low K+-EC following short and extended ischemia. Eur J Cardiothorac Surg 1997;12(5):771-9; discussion 779-80.

33. Arnaoutakis GJ, Allen JG, Merlo CA, Baumgartner WA, Conte JV, Shah AS. Low potassium dextran is superior to University of Wis-consin solution in high-risk lung transplant recipients. J Heart Lung Transplant 2010;29(12):1380-7.

34. Haverich A, Aziz S, Scott WC, Jamieson SW, Shumway NE. Improved lung preservation using Euro-Collins solution for flush-perfusion. Thorac Cardiovasc Surg 1986;34(6):368-76.

35. Wang LS, Nakamoto K, Hsieh CM, Miyoshi S, Cooper JD. Influence of temperature of flushing solution on lung preservation. Ann Thorac Surg 1993;55(3):711-5.

36. Steen S, Kimblad PO, Sjoberg T, Lindberg L, Ingemansson R, Massa G. Safe lung preservation for twenty-four hours with Perfadex. Ann Thorac Surg 1994;57(2):450-7.

37. Tachibana K, Imanaka H, Miyano H, Takeuchi M, Kumon K, Ando M, et al. Recruitment maneuver and high PEEP in a patient with severe reperfusion pulmonary edema after pulmonary thromboendarterectomy. Masui 2003;52(1):52-7.

38. Meyer KC, Love RB, Zimmerman JJ. The therapeutic potential of nitric oxide in lung transplantation. Chest 1998;113(5):1360-71.

39. Fukahara K, Murakami A, Watanabe G, Kotoh K, Misaki T. Inhaled nitric oxide after lung ischemia reperfusion; effect on hemody-namics and oxygen free radical scavenger system. Eur J Cardiothorac Surg 1997;11(2):343-9.

40. Pasero D, Martin EL, Davi A, Mascia L, Rinaldi M, Ranieri VM. The effects of inhaled nitric oxide after lung transplantation. Minerva Anestesiol 2010;76(5):353-61.

41. Yamashita H, Akamine S, Sumida Y, Inoue M, Sawada T, Nagayasu T, et al. Inhaled nitric oxide attenuates apoptosis in ischemia-reperfusion injury of the rabbit lung. Ann Thorac Surg 2004;78(1):292-7.

42. Rea RS, Ansani NT, Seybert AL. Role of inhaled nitric oxide in adult heart or lung transplant recipients. Ann Pharmacother 2005;39(5):913-7.

43. de Perrot M, Fischer S, Liu M, Jin R, Bai XH, Waddell TK, et al. Prostaglandin E1 protects lung transplants from ischemia-reperfu-sion injury: a shift from pro- to anti-inflammatory cytokines. Transplantation 2001;72(9):1505-12.

44. Matsuzaki Y, Waddell TK, Puskas JD, Hirai T, Nakajima S, Slutsky AS, et al. Amelioration of post-ischemic lung reperfusion injury by prostaglandin E1. Am Rev Respir Dis 1993;148(4 Pt 1):882-9.

45. Gillinov AM, DeValeria PA, Winkelstein JA, Wilson I, Curtis WE, Shaw D, et al. Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass. Ann Thorac Surg 1993;55(3):619-24.

46. Chai PJ, Nassar R, Oakeley AE, Craig DM, Quick G Jr, Jaggers J, et al. Soluble complement receptor-1 protects heart, lung, and cardiac myofilament function from cardiopulmonary bypass damage. Circulation 2000;101(5):541-6.

47. Curtin ML. Current status of platelet-activating factor antagonists. Expert Opin Ther Pat 1998;8(6):703-711. doi:10.1517/13543776.8.6.703.

48. Kurihara K, Wardlaw AJ, Moqbel R, Kay AB. Inhibition of platelet-activating factor (PAF)-induced chemotaxis and PAF bind-ing to human eosinophils and neutrophils by the specific ginkgolide-derived PAF antagonist, BN 52021. J Allergy Clin Immunol 1989;83(1):83-90.

49. Corcoran PC, Wang Y, Katz NM, St Louis JD, Foegh ML, Rajan SS, et al. Platelet activating factor antagonist enhances lung preserva-tion. J Surg Res 1992;52(6):615-20.

50. Muhlfeld C, Becker L, Bussinger C, Vollroth M, Nagib R, Schaefer IM, et al. Exogenous surfactant in ischemia/reperfusion: effects on endogenous surfactant pools. J Heart Lung Transplant 2010;29(3):327-34.

51. Dreyer N, Muhlfeld C, Fehrenbach A, Pech T, von Berg S, Nagib R, et al. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells. Respir Res 2008;9:5. doi: 10.1186/1465-9921-9-5.

52. Bittner HB, Lehmann S, Rastan A, Garbade J, Binner C, Mohr FW, et al. Outcome of extracorporeal membrane oxygenation as a bridge to lung transplantation and graft recovery. Ann Thorac Surg 2012;94(3):942-9; author reply 949-50.

53. Bermudez CA, Adusumilli PS, McCurry KR, Zaldonis D, Crespo MM, Pilewski JM, et al. Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival. Ann Thorac Surg 2009;87(3):854-60.

54. Oto T, Rosenfeldt F, Rowland M, Pick A, Rabinov M, Preovolos A, et al. Extracorporeal membrane oxygenation after lung transplan-tation: evolving technique improves outcomes. Ann Thorac Surg 2004;78(4):1230-5.

55. Patil NP, Mohite PN, Reed A, Popov AF, Simon AR. Modified technique using Novalung as bridge to transplant in pulmonary hyper-tension. Ann Thorac Surg 2015;99(2):719-21.

56. Tsuchihashi S, Fondevila C, Kupiec-Weglinski JW. Heme oxygenase system in ischemia and reperfusion injury. Ann Transplant 2004;9(1):84-7.

57. Simon R. Post-conditioning and reperfusion injury in the treatment of stroke. Dose Response 2014;12(4):590-9.

58. Soncul H, Oz E, Kalaycioglu S. Role of ischemic preconditioning on ischemia-reperfusion injury of the lung. Chest 1999;115(6):1672-7.

59. Gao M, Liu D. Ischemic preconditioning may attenuate lung ischemia-reperfusion injury partly by stimulating autophagy. J Formos Med Assoc 2015;114(8):677-8.

60. Xu B, Gao X, Xu J, Lei S, Xia ZY, Xu Y, et al. Ischemic postconditioning attenuates lung reperfusion injury and reduces systemic proinflammatory cytokine release via heme oxygenase 1. J Surg Res 2011;166(2):e157-64.

61. Daddi N, Suda T, D’Ovidio F, Kanaan SA, Tagawa T, Grapperhaus K, et al. Recipient intramuscular cotransfection of naked plasmid transforming growth factor β1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury. J Thorac Cardiovasc Surg 2002;124(2):259-69.

62. Fischer S, De Perrot M, Liu M, MacLean AA, Cardella JA, Imai Y, et al. Interleukin 10 gene transfection of donor lungs ameliorates posttransplant cell death by a switch from cellular necrosis to apoptosis. J Thorac Cardiovasc Surg 2003;126(4):1174-80.

63. de Perrot M, Fischer S, Liu M, Imai Y, Martins S, Sakiyama S, et al. Impact of human interleukin-10 on vector-induced inflammation and early graft function in rat lung transplantation. Am J Respir Cell Mol Biol 2003;28(5):616-25.

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