Ischaemic Preconditioning: The Rationale and Evidence-Based Outcomes

  • George HamiltonEmail author


Reperfusion injury is a process well recognised and understood by vascular surgeons where return of arterialised blood flow to a previously ischaemic organ or tissue often results in a complex pathophysiological cascade ending in potentially irreversible cellular damage. The sequelae of this process are frequently seen in vascular surgery after reperfusion of a previously ischaemic lower limb. The resulting profoundly acute inflammatory syndrome gives rise to raised compartmental pressure within the muscles of the lower limb requiring fasciotomy. Reperfusion injury however can develop in several other surgical scenarios including coronary artery bypass grafting and other cardiac interventions, organ transplantation and major vascular surgery, in particular aortic aneurysm repair and carotid endarterectomy. Obviously in these scenarios, fasciotomy is not an option, and since the 1980s, there has been research into avoiding or at least mitigating reperfusion injury.


  1. 1.
    Ovize M, Mewton N. Interventional cardiology: ischaemic POSTconditioning–a long harvest for a little corn. Nat Rev Cardiol. 2014;11:8–10.CrossRefGoogle Scholar
  2. 2.
    Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischaemic “preconditioning” protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993;87:893–9.CrossRefGoogle Scholar
  3. 3.
    Menting TP, Wever KE, Ozdemir-van Brunschot DM, Van der Vliet DJ, Rovers MM, Warle MC. Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury. Cochrane Database Syst Rev. 2017;3:CD010777. Scholar
  4. 4.
    Kharbanda RK, Nielsen TT, Redington AN. Translation of remote ischaemic preconditioning into clinical practice. Lancet. 2009;374:1557–65.CrossRefGoogle Scholar
  5. 5.
    Xing D, Zhang R, Li S, Huang P, Luo C, Hei Z, Xia Z, Gan X. Pivotal role of mast cell carboxypeptidase A in mediating protection against small intestinal ischemia-reperfusion injury in rats after ischemic preconditioning. J Surg Res. 2014;192:177–86.CrossRefGoogle Scholar
  6. 6.
    Gi YY, Wang ZD, Wang SF, Wang WT, Yang ZA, Zhou XR, Lei NN, Yue WN. Ischemic preconditioning ameliorates intestinal injury induced by ischemia-reperfusion in rats. World J Gastro Enterol. 2015;21:8081–8.CrossRefGoogle Scholar
  7. 7.
    Sardar P, Chatterjee S, Kundu A, et al. Remote ischemic preconditioning in patients undergoing cardiovascular surgery: evidence from a metanalysis of randomised controlled trial. Int J Cardiol. 2016;221:34–41.CrossRefGoogle Scholar
  8. 8.
    Kottenberg E, Thielmann M, Bergmann L, et al. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol–a clinical trial. Acta Anaesthesiol Scand. 2012;56(1):30–8.CrossRefGoogle Scholar
  9. 9.
    Ali ZA, Callaghan CJ, Lim E, et al. Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. Circulation. 2007;116(11 suppl):I98–I105.PubMedGoogle Scholar
  10. 10.
    Walsh SR, Sadat U, Boyle JR, et al. Remote ischemic preconditioning for renal protection during elective open infrarenal abdominal aortic aneurysm repair: randomized controlled trial. Vasc Endovasc Surg. 2010;44(5):334–40.CrossRefGoogle Scholar
  11. 11.
    Murphy N, Vijayan A, Frohlich S, et al. Remote ischemic preconditioning does not affect the incidence of acute kidney injury after elective abdominal aortic aneurysm repair. J Cardiothorac Vasc Anesth. 2014;28(5):1285–92.CrossRefGoogle Scholar
  12. 12.
    Li C, Li YS, Xu M, et al. Limb remote ischemic preconditioning for intestinal and pulmonary protection during elective open infrarenal abdominal aortic aneurysm repair: a randomized controlled trial. Anesthesiology. 2013;118(4):842–52.CrossRefGoogle Scholar
  13. 13.
    Walsh SR, Nouraei SA, Tang TY, Sadat U, Carpenter RH, Gaunt ME. Remote ischemic preconditioning for cerebral and cardiac protection during carotid endarterectomy: results from a pilot randomized clinical trial. Vasc Endovasc Surg. 2010;44(6):434–9.CrossRefGoogle Scholar
  14. 14.
    Walsh SR, Boyle JR, Tang TY, et al. Remote ischemic preconditioning for renal and cardiac protection during endovascular aneurysm repair: a randomized controlled trial. J Endovasc Ther. 2009;16(6):680–9.CrossRefGoogle Scholar
  15. 15.
    Healy DA, Boyle E, McCartan D, et al. A multi center pilot randomized controlled trial of remote ischemic preconditioning in major vascular surgery. Vasc Endovasc Surg. 2015;49(8):220–7.CrossRefGoogle Scholar
  16. 16.
    Mouton R, Pollock J, Soar J, Mitchell DC, Rogers CA. Remote ischaemic preconditioning versus sham procedure for abdominal aortic aneurysm repair: an external feasibility randomized controlled trial. Trials. 2015;16:377.CrossRefGoogle Scholar
  17. 17.
    Garcia S, Rector TS, Zakharova M, et al. Cardiac remote ischemic preconditioning prior to elective vascular surgery (CRIPES): a prospective, randomized, sham-controlled phase II clinical trial. J Am Heart Assoc. 2016;5(10):e003916.CrossRefGoogle Scholar
  18. 18.
    Thomas KN, Cotter JD, Williams MJ, van Rij AM. Repeated episodes of remote ischemic preconditioning for the prevention of myocardial injury in vascular surgery. Vasc Endovasc Surg. 2016;50(3):140–6.CrossRefGoogle Scholar
  19. 19.
    Coverdale NS, Hamilton A, Petsikas D, McClure RS, Malik P, Milne B, Saha T, Zelt D, Brown P, Payne DM. Remote ischaemic preconditioning in high risk cardiovascular surgery patients: a randomised controlled trial. Semin Thorac Cardiovasc Surg. 2017;30(1):26–33.CrossRefGoogle Scholar
  20. 20.
    Twine CP, Ferguson S, Boyle JR. Review: benefits of remote ischaemic preconditioning in vascular surgery. Eur J Vasc Endovasc Surg. 2014;48(2):215–9. Scholar
  21. 21.
    Desai M, Gurusamy KS, Ghanbari H, Hamilton G, Seifalian AM. Remote ischaemic preconditioning versus no remote ischaemic preconditioning for vascular and endovascular surgical procedures. Cochrane Database Syst Rev. 2011;12:CD008472.Google Scholar
  22. 22.
    Brevoord D, Kranke P, Kuijpers M, Weber N, Hollmann M, Preckel B. Remote ischemic conditioning to protect against ischemia-reperfusion injury: a systematic review and metanalysis. PLoS One. 2012;7:e42179.CrossRefGoogle Scholar
  23. 23.
    Li L, Li G, Yu C, Li Y. The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: a meta-analysis. J Cardiothorac Surg. 2013;8:43.CrossRefGoogle Scholar
  24. 24.
    Takagi H, Umemoto T. Remote ischemic preconditioning for cardiovascular surgery: an updated meta-analysis of randomized trials. Vasc Endovasc Surg. 2011;45:511e3.Google Scholar
  25. 25.
    Ungi I, Ungi T, Ruzsa Z, et al. Hypercholesterolaemia attenuates the anti-ischaemic effect of preconditioning during coronary angioplasty. Chest. 2005;128:1623–8.CrossRefGoogle Scholar
  26. 26.
    Ishihara M, Inoue I, Kawagoe T, et al. Diabetes mellitus prevents ischaemic preconditioning in patients with a first acute anterior wall myocardial infarction. J Am Coll Cardiol. 2001;38:1007–11.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Royal Free London NHS Foundation TrustLondonUK
  2. 2.Great Ormond Street Hospital NHS Foundation TrustLondonUK
  3. 3.Medical SchoolUniversity College LondonLondonUK

Personalised recommendations