Effect of Remote Ischemic Preconditioning on Myocardial and Renal Injury: Meta-Analysis of Randomized Controlled Trials


Gaurav Alreja, MD1, Diogo Bugano, MD2, Amir Lotfi, MD1


  1. Mohammed AA, Agnihotri AK, van Kimmenade RR, et al. Prospective, comprehensive assessment of cardiac troponin T testing after coronary artery bypass graft surgery. Circulation. 2009;120(10):843-850.
  2. Croal BL, Hillis GS, Gibson PH, et al. Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation. 2006;114(14):1468-1475.
  3. Ricciardi MJ, Davidson CJ, Gubernikoff G, et al. Troponin I elevation and cardiac events after percutaneous coronary intervention. Am Heart J. 2003;145(3):522-528.
  4. Winkel TA, Schouten O, van Kuijk JP, Verhagen HJ, Bax JJ, Poldermans D. Perioperative asymptomatic cardiac damage after endovascular abdominal aneurysm repair is associated with poor long-term outcome. J Vasc Surg. 2009;50(4):749-754.
  5. Mantese VA, Timaran CH, Chiu D, Begg RJ, Brott TG. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): stenting versus carotid endarterectomy for carotid disease. Stroke. 2010;41(10 Suppl):S31-S34.
  6. Mair J, Hammerer-Lercher A. Markers for perioperative myocardial ischemia: what both interventional cardiologists and cardiac surgeons need to know. Heart Surg Forum. 2005;8(5):E319-E325.
  7. Fellahi JL, Hedoire F, Le Manach Y, Monier E, Guillou L, Riou B. Determination of the threshold of cardiac troponin I associated with an adverse postoperative outcome after cardiac surgery: a comparative study between coronary artery bypass graft, valve surgery, and combined cardiac surgery. Crit Care. 2007;11(5):R106.
  8. Domanski MJ, Mahaffey K, Hasselblad V, et al. Association of myocardial enzyme elevation and survival following coronary artery bypass graft surgery. JAMA. 2011;305(6):585-591.
  9. Ishani A, Nelson D, Clothier B, et al. The magnitude of acute serum creatinine increase after cardiac surgery and the risk of coronary artery disease, progression of kidney disease, and death. Arch Intern Med. 2011;171(3):226-233.
  10. Jenkins DP, Pugsley WB, Alkhulaifi AM, Kemp M, Hooper J, Yellon DM. Ischemic preconditioning reduces troponin T release in patients undergoing coronary artery bypass surgery. Heart. 1997;77(4):314-318.
  11. Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B. Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol. 1997;273(4 Pt 2):H1707-H1712. 
  12. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. Myocardial protection by brief ischemia in noncardiac tissue. Circulation. 1996;94(9):2193-2200.
  13. Tang ZL, Dai W, Li YJ, Deng HW. Involvement of capsaicin-sensitive sensory nerves in early and delayed cardioprotection induced by a brief ischemia of the small intestine. Naunyn Schmiedebergs Arch Pharmacol. 1999;359(3):243-247.
  14. Schoemaker RG, van Heijningen CL. Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol. 2000;278(5):H1571-H1576.
  15. Liem DA, Verdouw PD, Ploeg H, Kazim S, Duncker DJ. Sites of action of adenosine in interorgan preconditioning of the heart. Am J Physiol Heart Circ Physiol. 2002;283(1):H29-H37.
  16. Xiao L, Lu R, Hu CP, Deng HW, Li YJ. Delayed cardioprotection by intestinal preconditioning is mediated by calcitonin gene-related peptide. Eur J Pharmacol. 2001;427(2):131-135.
  17. Wolfrum S, Schneider K, Heidbreder M, Nienstedt J, Dominiak P, Dendorfer A. Remote preconditioning protects the heart by activating myocardial PKCepsilon-isoform. Cardiovasc Res. 2002;55(3):583-589.


  1. Patel HH, Moore J, Hsu AK, Gross GJ. Cardioprotection at a distance: mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism. J Mol Cell Cardiol. 2002;34(10):1317-1323.
  2. Wolfrum S, Nienstedt J, Heidbreder M, Schneider K, Dominiak P, Dendorfer A. Calcitonin gene related peptide mediates cardioprotection by remote preconditioning. Regul Pept. 2005;127(1-3):217-224.
  3. Hajrasouliha AR, Tavakoli S, Ghasemi M, et al. Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB(2) receptors in the rat heart. Eur J Pharmacol. 2008;579(1-3):246-252.
  4. Heidbreder M, Naumann A, Tempel K, Dominiak P, Dendorfer A. Remote vs. ischemic preconditioning: the differential role of mitogen-activated protein kinase pathways. Cardiovasc Res. 2008;78(1):108-115.
  5. Ding YF, Zhang MM, He RR. Role of renal nerve in cardioprotection provided by renal ischemic preconditioning in anesthetized rabbits. Sheng Li Xue Bao. 2001;53(1):7-12.
  6. McClanahan T, Nao B, Wolke L, Martin BJ, Mezt TE. Brief renal occlusion and reperfusion reduces myocardial infarct size in rabbits (Abstr). FASEB J. 1993;7:A18.
  7. Takaoka A, Nakae I, Mitsunami K, et al. Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of “remote preconditioning.” J Am Coll Cardiol. 1999;33(2):556-564.
  8. Dickson EW, Reinhardt CP, Renzi FP, Becker RC, Porcaro WA, Heard SO. Ischemic preconditioning may be transferable via whole blood transfusion: preliminary evidence. J Thromb Thrombolysis. 1999;8(2):123-129.
  9. Singh D, Chopra K. Evidence of the role of angiotensin AT(1) receptors in remote renal preconditioning of myocardium. Methods Find Exp Clin Pharmacol. 2004;26(2):117-122.
  10. Lang SC, Elsasser A, Scheler C, et al. Myocardial preconditioning and remote renal preconditioning — identifying a protective factor using proteomic methods? Basic Res Cardiol. 2006;101(2):149-158.
  11. Kant R, Diwan V, Jaggi AS, Singh N, Singh D. Remote renal preconditioning induced cardioprotection: a key role of hypoxia inducible factor-prolyl 4-hydroxylases. Mol Cell Biochem. 2008;312(1-2):25-31.
  12. Weinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser RH. Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway. Cardiovasc Res. 2002;55(3):590-601.
  13. Weinbrenner C, Schulze F, Sarvary L, Strasser RH. Remote preconditioning by infrarenal aortic occlusion is operative via delta1-opioid receptors and free radicals in vivo in the rat heart. Cardiovasc Res. 2004;61(3):591-599.
  14. Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation. 1997;96(5):1641-1646.
  15. Dong JH, Liu YX, Ji ES, He RR. [Limb ischemic preconditioning reduces infarct size following myocardial ischemia-reperfusion in rats]. Sheng Li Xue Bao. 2004;56(1):41-46.
  16. Konstantinov IE, Li J, Cheung MM, et al. Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a K(ATP)channel-dependent mechanism. Transplantation. 2005;79(12):1691-1695.


  1. Kristiansen SB, Henning O, Kharbanda RK, et al. Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol. 2005;288(3):H1252-H1256.
  2. Tokuno S, Hinokiyama K, Tokuno K, Lowbeer C, Hansson LO, Valen G. Spontaneous ischemic events in the brain and heart adapt the hearts of severely atherosclerotic mice to ischemia. Arterioscler Thromb Vasc Biol. 2002;22(6):995-1001.
  3. Zhang SZ, Wang NF, Xu J, et al. Kappa-opioid receptors mediate cardioprotection by remote preconditioning. Anesthesiology. 2006;105(3):550-556.
  4. Konstantinov IE, Arab S, Li J, et al. The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium. J Thorac Cardiovasc Surg. 2005;130(5):1326-1332.
  5. Peralta C, Fernandez L, Panes J, et al. Preconditioning protects against systemic disorders associated with hepatic ischemia-reperfusion through blockade of tumor necrosis factor-induced P-selectin up-regulation in the rat. Hepatology. 2001;33(1):100-113.
  6. Kharbanda RK, Mortensen UM, White PA, et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation. 2002;106(23):2881-2883.
  7. Loukogeorgakis SP, Panagiotidou AT, Broadhead MW, Donald A, Deanfield JE, MacAllister RJ. Remote ischemic preconditioning provides early and late protection against endothelial ischemia-reperfusion injury in humans: role of the autonomic nervous system. J Am Coll Cardiol. 2005;46(3):450-456.
  8. Loukogeorgakis SP, Williams R, Panagiotidou AT, et al. Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation. 2007;116(12):1386-1395.
  9. Rahman IA, Mascaro JG, Steeds RP, et al. Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation. 2010;122(11 Suppl):S53-S59.
  10. Hong DM, Mint JJ, Kim JH, et al. The effect of remote ischemic preconditioning on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery. Anaesth Intensive Care. 2010;38(5):924-929.
  11. Botker HE. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010;375(9716):727-734.
  12. Hoole SP. Cardiac remote ischemic preconditioning in coronary stenting (CRISP Stent) study: a prospective, randomized control trial. Circulation. 2009;119(6):820-827.
  13. Iliodromitis EK, Kyrzopoulos S, Paraskevaidis IA, et al. Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischemic preconditioning? Heart. 2006;92(12):1821-1826.
  14. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet. 1999;354(9193):1896-1900.    
  15. Bignami E, Landoni G, Crescenzi G, et al. Role of cardiac biomarkers (troponin I and CK-MB) as predictors of quality of life and long-term outcome after cardiac surgery. Ann Card Anaesth. 2009;12(1):22-26.
  16. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.


Post new comment

  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

More information about formatting options

Enter the characters shown in the image.