Iranian Journal of Medical Sciences

Document Type: Original Article(s)


1 Shiraz Anesthesiology and Critical Care Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

2 Shiraz Anesthesiology and Critical Care Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran;

3 Department of Cardiac Surgery, Faghihi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran


Background: The cardioprotective effect of ischemic preconditioning has been known for many years. Since the temporary ischemia in the heart may cause lethal cardiac effects, the idea of creating ischemia in organs far from the heart such as limbs was raised as remote ischemic preconditioning (RIPC). We hypothesized that the extension of RIPC has more cardioprotective effect in patients undergoing coronary artery bypass graft (CABG) surgeries.Methods: In this triple-blind randomized clinical trial study, 96 patients were randomly divided into 3 groups and two blood pressure cuffs were placed on both upper and lower extremities. In group A, only upper extremity cuff and in group B upper limb and lower limb cuff was inflated intermittently and group C was the control group. RIPC was induced with three 5-min cycles of cuff inflation about 100 mmHg over the initial systolic blood pressure before starting cardiopulmonary bypass. The primary endpoints were troponin I and creatine phosphokinasemyoglobin isoenzyme (CK-MB).Results: Six hours after the termination of CPB, there was a peak release of the troponin I level in all groups (group A=4.90 ng/ml, group B=4.40 ng/ml, and group C=4.50 ng/ml). There was a rise in plasma CK-MB in all groups postoperatively and there were not any significant differences in troponin I and CK-MB release between the three groups.Conclusion: RIPC induced by upper and lower limb ischemia does not reduce postoperative myocardial enzyme elevation in adult patients undergoing CABG.Trial Registration Number: IRCT2012071710311N1


  1. Domanski MJ, Mahaffey K, Hasselblad V, Brener SJ, Smith PK, Hillis G, et al. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA. 2011;305:585-91. doi: 10.1001/jama.2011.99. PubMed PMID: 21304084.
  2. Yau JM, Alexander JH, Hafley G, Mahaffey KW, Mack MJ, Kouchoukos N, et al. Impact of perioperative myocardial infarction on angiographic and clinical outcomes following coronary artery bypass grafting (from PRoject of Ex-vivo Vein graft ENgineering via Transfection [PREVENT] IV). Am J Cardiol. 2008;102:546-51. doi: 10.1016/j.amjcard.2008.04.069. PubMed PMID: 18721510.
  3. Mentzer RM, Jr. Myocardial protection in heart surgery. J Cardiovasc Pharmacol Ther. 2011;16:290-7. doi: 10.1177/1074248411410318. PubMed PMID: 21821531.
  4. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation. 1993;87:893-9. doi: 10.1161/01.CIR.87.3.893. PubMed PMID: 7680290.
  5. Frank A, Bonney M, Bonney S, Weitzel L, Koeppen M, Eckle T. Myocardial ischemia reperfusion injury: from basic science to clinical bedside. Semin Cardiothorac Vasc Anesth. 2012;16:123-32. doi: 10.1177/1089253211436350. PubMed PMID: 22368166; PubMed Central PMCID: PMC3457795.
  6. Ramzy D, Rao V, Weisel RD. Clinical applicability of preconditioning and postconditioning: the cardiothoracic surgeons's view. Cardiovasc Res. 2006;70:174-80. doi: 10.1016/j.cardiores.2006.01.020. PubMed PMID: 16524563.
  7. Takagi H, Manabe H, Kawai N, Goto SN, Umemoto T. Review and meta-analysis of randomized controlled clinical trials of remote ischemic preconditioning in cardiovascular surgery. Am J Cardiol. 2008;102:1487-8. doi: 10.1016/j.amjcard.2008.07.036. PubMed PMID: 19026301.
  8. Takagi H, Umemoto T. Remote ischemic preconditioning for cardiovascular surgery: an updated meta-analysis of randomized trials. Vasc Endovascular Surg. 2011;45:511-3. doi: 10.1177/1538574410379654. PubMed PMID: 21646235.
  9. Rahman IA, Mascaro JG, Steeds RP, Frenneaux MP, Nightingale P, Gosling P, et al. Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation. 2010;122:S53-9. doi: 10.1161/CIRCULATIONAHA.109.926667. PubMed PMID: 20837926.
  10. Karuppasamy P, Chaubey S, Dew T, Musto R, Sherwood R, Desai J, et al. Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation? Basic Res Cardiol. 2011;106:511-9. doi: 10.1007/s00395-011-0185-9. PubMed PMID: 21544683.
  11. Wu Q, Gui P, Wu J, Ding D, Purusram G, Dong N, et al. Effect of limb ischemic preconditioning on myocardial injury in patients undergoing mitral valve replacement surgery. -A randomized controlled trial. Circ J. 2011;75:1885-9. PubMed PMID: 21697609.
  12. Xie JJ, Liao XL, Chen WG, Huang DD, Chang FJ, Chen W, et al. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing heart valve surgery: randomised controlled trial. Heart. 2012;98:384-8. doi: 10.1136/heartjnl-2011-300860. PubMed PMID: 22107759.
  13. Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, et al. Remote Ischemic Preconditioning Applied during Isoflurane Inhalation Provides No Benefit to the Myocardium of Patients Undergoing On-pump Coronary Artery Bypass Graft SurgeryLack of Synergy or Evidence of Antagonism in Cardioprotection? American Society of Anesthesiologists. 2012;116:296-310.
  14. Lomivorotov VV, Shmyrev VA, Nepomnyaschih VA, Ponomarev DN, Knyazkova LG, Lomivorotov VN, et al. Remote ischaemic preconditioning does not protect the heart in patients undergoing coronary artery bypass grafting. Interact Cardiovasc Thorac Surg. 2012;15:18-22. doi: 10.1093/icvts/ivs118. PubMed PMID: 22493101; PubMed Central PMCID: PMC3380992.
  15. Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, 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;56:30-8. doi: 10.1111/j.1399-6576.2011.02585.x. PubMed PMID: 22103808.
  16. Young PJ, Dalley P, Garden A, Horrocks C, La Flamme A, Mahon B, 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. 2012;107:256. doi: 10.1007/s00395-012-0256-6. PubMed PMID: 22406977.
  17. Wang L, Oka N, Tropak M, Callahan J, Lee J, Wilson G, et al. Remote ischemic preconditioning elaborates a transferable blood-borne effector that protects mitochondrial structure and function and preserves myocardial performance after neonatal cardioplegic arrest. J Thorac Cardiovasc Surg. 2008;136:335-42. doi: 10.1016/j.jtcvs.2007.12.055. PubMed PMID: 18692639.
  18. Kharbanda RK, Nielsen TT, Redington AN. Translation of remote ischaemic preconditioning into clinical practice. Lancet. 2009;374:1557-65. doi: 10.1016/S0140-6736(09)61421-5. PubMed PMID: 19880021.
  19. Konstantinov IE, Arab S, Kharbanda RK, Li J, Cheung MM, Cherepanov V, et al. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004;19:143-50. doi: 10.1152/physiolgenomics.00046.2004. PubMed PMID: 15304621.
  20. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. Myocardial protection by brief ischemia in noncardiac tissue. Circulation. 1996;94:2193-200. doi: 10.1161/01.CIR.94.9.2193. PubMed PMID: 8901671.
  21. Lang SC, Elsasser A, Scheler C, Vetter S, Tiefenbacher CP, Kubler W, et al. Myocardial preconditioning and remote renal preconditioning--identifying a protective factor using proteomic methods? Basic Res Cardiol. 2006;101:149-58. doi: 10.1007/s00395-005-0565-0. PubMed PMID: 16283592.
  22. Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002;106:2881-3. doi: 10.1161/01.CIR.0000043806.51912.9B. PubMed PMID: 12460865.
  23. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet. 2007;370:575-9. doi: 10.1016/S0140-6736(07)61296-3. PubMed PMID: 17707752.
  24. Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, et al. Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol. 2010;105:657-64. doi: 10.1007/s00395-010-0104-5. PubMed PMID: 20495811.
  25. Rahman I, Bonser RS. Remote ischaemic preconditioning: the current best hope for improved myocardial protection in cardiac surgery? Heart. 2009;95:1553-5. doi: 10.1136/hrt.2008.159988. PubMed PMID: 19628467.
  26. Hoole SP, Khan SN, White PA, Heck PM, Kharbanda RK, Densem CG, et al. Remote ischaemic pre-conditioning does not attenuate ischaemic left ventricular dysfunction in humans. Eur J Heart Fail. 2009;11:497-505. doi: 10.1093/eurjhf/hfp040. PubMed PMID: 19386814.
  27. Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. 2006;47:2277-82. doi: 10.1016/j.jacc.2006.01.066. PubMed PMID: 16750696.
  28. Hong DM, Mint JJ, Kim JH, Sohn IS, Lim TW, Lim YJ, et al. The effect of remote ischaemic preconditioning on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery. Anaesth Intensive Care. 2010;38:924-9. PubMed PMID: 20865880.
  29. Pilcher JM, Young P, Weatherall M, Rahman I, Bonser RS, Beasley RW. A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery. J R Soc Med. 2012;105:436-45. doi: 10.1258/jrsm.2012.120049. PubMed PMID: 23104947; PubMed Central PMCID: PMC3480853.
  30. Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008;79:377-86. doi: 10.1093/cvr/cvn114. PubMed PMID: 18456674.
  31. Zhou C, Liu Y, Yao Y, Zhou S, Fang N, Wang W, et al. beta-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials. J Cardiothorac Vasc Anesth. 2013;27:305-11. doi: 10.1053/j.jvca.2012.09.028. PubMed PMID: 23276595.