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A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol

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Basic Research in Cardiology Aims and scope Submit manuscript

An Invited Editorial to this article was published on 20 March 2012

An Invited Editorial to this article was published on 18 March 2012

Abstract

The efficacy of remote ischemic preconditioning (RIPC) in high-risk cardiac surgery is uncertain. In this study, 96 adults undergoing high-risk cardiac surgery were randomised to RIPC (3 cycles of 5 min of upper-limb ischemia induced by inflating a blood pressure cuff to 200 mmHg with 5 min of reperfusion) or control. Main endpoints were plasma high-sensitivity troponin T (hsTNT) levels at 6 and 12 h, worst post-operative acute kidney injury (AKI) based on RIFLE criteria, and noradrenaline duration. hsTNT levels were log-normally distributed and higher with RIPC than control at 6-h post cross-clamp removal [810 ng/ml (IQR 527–1,724) vs. 634 ng/ml (429–1,012); ratio of means 1.41 (99.17% CI 0.92–2.17); P=0.04] and 12 h [742 ng/ml (IQR 427–1,700) vs. 514 ng/ml (IQR 356–833); ratio of means 1.56 (99.17% CI 0.97–2.53); P=0.01]. After adjustment for baseline confounders, the ratio of means of hsTNT at 6 h was 1.23 (99.17% CI 0.88–1.72; P=0.10) and at 12 h was 1.30 (99.17% CI 0.92–1.84; P=0.05). In the RIPC group, 35/48 (72.9%) had no AKI, 5/48 (10.4%) had AKI risk, and 8/48 (16.7%) had either renal injury or failure compared to the control group where 34/48 (70.8%) had no AKI, 7/48 (14.6%) had AKI risk, and 7/48 (14.6%) had renal injury or failure (Chi-squared 0.41; two degrees of freedom; P = 0.82). RIPC increased post-operative duration of noradrenaline support [21 h (IQR 7–45) vs. 9 h (IQR 3–19); ratio of means 1.70 (99.17% CI 0.86–3.34); P=0.04]. RIPC does not reduce hsTNT, AKI, or ICU-support requirements in high-risk cardiac surgery.

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References

  1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212. doi:10.1186/cc2872

    Article  PubMed  Google Scholar 

  2. Birnbaum Y, Hale SL, Kloner RA (1997) 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 96:1641–1646. doi:10.1161/01.CIR.96.5.1641

    PubMed  CAS  Google Scholar 

  3. Botker HE, Kharbanda R, Schmidt MR, Bottcher M, Kaltoft AK, Terkelsen CJ, Munk K, Andersen NH, Hansen TM, Trautner S, Lassen JF, Christiansen EH, Krusell LR, Kristensen SD, Thuesen L, Nielsen SS, Rehling M, Sorensen HT, Redington AN, Nielsen TT (2010) 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 375:727–734. doi:10.1016/S0140-6736(09)62001-8

    Article  PubMed  Google Scholar 

  4. Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK (2011) Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3 K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 106:135–145. doi:10.1007/s00395-010-0133-0

    Article  PubMed  CAS  Google Scholar 

  5. Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN (2006) Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 47:2277–2282. doi:10.1016/j.jacc.2006.01.066

    Article  PubMed  Google Scholar 

  6. Choi YS, Shim JK, Kim JC, Kang KS, Seo YH, Ahn KR, Kwak YL (2011) Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 142:148–154. doi:10.1016/j.jtcvs.2010.11.018

    Article  PubMed  Google Scholar 

  7. Fellahi JL, Hanouz JL, Gue X, Monier E, Guillou L, Riou B (2008) Kinetic analysis of cardiac troponin I release is no more accurate than a single 24-h measurement in predicting in-hospital outcome after cardiac surgery. Eur J Anaesthesiol 25:490–497. doi:10.1017/S0265021508003827

    Article  PubMed  CAS  Google Scholar 

  8. Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–2200

    PubMed  CAS  Google Scholar 

  9. Gunaydin B, Cakici I, Soncul H, Kalaycioglu S, Cevik C, Sancak B, Kanzik I, Karadenizli Y (2000) Does remote organ ischaemia trigger cardiac preconditioning during coronary artery surgery? Pharmacol Res 41:493–496. doi:10.1006/phrs.1999.0611

    Article  PubMed  CAS  Google Scholar 

  10. Hanouz JL, Yvon A, Massetti M, Lepage O, Babatasi G, Khayat A, Bricard H, Gerard JL (2002) Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro. Anesthesiology 97:33–41

    Article  PubMed  CAS  Google Scholar 

  11. Hausenloy DJ, Baxter G, Bell R, Botker HE, Davidson SM, Downey J, Heusch G, Kitakaze M, Lecour S, Mentzer R, Mocanu MM, Ovize M, Schulz R, Shannon R, Walker M, Walkinshaw G, Yellon DM (2010) Translating novel strategies for cardioprotection: the Hatter workshop recommendations. Basic Res Cardiol 105:677–686. doi:10.1007/s00395-010-0121-4

    Article  PubMed  Google Scholar 

  12. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S, Hayward M, Keogh B, MacAllister RJ, Yellon DM (2007) Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 370:575–579. doi:10.1016/S0140-6736(07)61296-3

    Article  PubMed  Google Scholar 

  13. Heusch G, Musiolik J, Kottenberg E, Peters J, Jakob H, Thielmann M (2012) STAT5 activation and cardioprotection by remote ischemic preconditioning in humans. Circ Res 110:111–115. doi:10.1161/CIRCRESAHA.111.259556

    Article  PubMed  CAS  Google Scholar 

  14. Hong DM, Mint JJ, Kim JH, Sohn IS, Lim TW, Lim YJ, Bahk JH, Jeon Y (2010) The effect of remote ischaemic preconditioning on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery. Anaesth Intensive Care 38:924–929

    PubMed  CAS  Google Scholar 

  15. Hu ZY, Liu J (2009) Mechanism of cardiac preconditioning with volatile anaesthetics. Anaesth Intensive Care 37:532–538

    PubMed  Google Scholar 

  16. Karuppasamy P, Chaubey S, Dew T, Musto R, Sherwood R, Desai J, John L, Shah AM, Marber MS, Kunst G (2011) Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation? Basic Res Cardiol 106:511–519. doi:10.1007/s00395-011-0185-9

    Article  PubMed  CAS  Google Scholar 

  17. Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J (2012) Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol: a clinical trial. Acta Anaesthesiol Scand 56:30–38. doi:10.1111/j.1399-6576.2011.02585.x

    Article  PubMed  CAS  Google Scholar 

  18. Lange M, Redel A, Smul TM, Lotz C, Nefzger T, Stumpner J, Blomeyer C, Gao F, Roewer N, Kehl F (2009) Desflurane-induced preconditioning has a threshold that is lowered by repetitive application and is mediated by beta 2-adrenergic receptors. J Cardiothorac Vasc Anesth 23:607–613. doi:10.1053/j.jvca.2009.01.016

    Article  PubMed  CAS  Google Scholar 

  19. Lange M, Smul TM, Blomeyer CA, Redel A, Klotz KN, Roewer N, Kehl F (2006) Role of the beta1-adrenergic pathway in anesthetic and ischemic preconditioning against myocardial infarction in the rabbit heart in vivo. Anesthesiology 105:503–510

    Article  PubMed  CAS  Google Scholar 

  20. Li L, Luo W, Huang L, Zhang W, Gao Y, Jiang H, Zhang C, Long L, Chen S (2010) Remote perconditioning reduces myocardial injury in adult valve replacement: a randomized controlled trial. J Surg Res 164:e21–e26. doi:10.1016/j.jss.2010.06.016

    Article  PubMed  Google Scholar 

  21. Lim SY, Yellon DM, Hausenloy DJ (2010) The neural and humoral pathways in remote limb ischemic preconditioning. Basic Res Cardiol 105:651–655. doi:10.1007/s00395-010-0099-y

    Article  PubMed  Google Scholar 

  22. Liu Y, Sato T, O’Rourke B, Marban E (1998) Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection? Circulation 97:2463–2469. doi:10.1161/01.CIR.97.24.2463

    PubMed  CAS  Google Scholar 

  23. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R (1999) European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 16:9–13. doi:10.1016/S1010-7940(99)00134-7

    Article  PubMed  CAS  Google Scholar 

  24. Nesher N, Alghamdi AA, Singh SK, Sever JY, Christakis GT, Goldman BS, Cohen GN, Moussa F, Fremes SE (2008) Troponin after cardiac surgery: a predictor or a phenomenon? Ann Thorac Surg 85:1348–1354. doi:10.1016/j.athoracsur.2007.12.077

    Article  PubMed  Google Scholar 

  25. Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B (1997) Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol 273:H1707–H1712

    PubMed  CAS  Google Scholar 

  26. Peters J (2011) Remote ischaemic preconditioning of the heart: remote questions, remote importance, or remote preconditions? Basic Res Cardiol 106:507–509. doi:10.1007/s00395-011-0187-7

    Article  PubMed  Google Scholar 

  27. Rahman IA, Mascaro JG, Steeds RP, Frenneaux MP, Nightingale P, Gosling P, Townsend P, Townend JN, Green D, Bonser RS (2010) Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation 122:S53–S59. doi:10.1161/circulationaha.109.926667

    Article  PubMed  Google Scholar 

  28. Schultz JE, Hsu AK, Gross GJ (1996) Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart. Circ Res 78:1100–1104

    PubMed  CAS  Google Scholar 

  29. Longacre LS, Kloner RA, Arai AE, Baines CP, Bolli R, Braunwald E, Downey J, Gibbons RJ, Gottlieb RA, Heusch G, Jennings RB, Lefer DJ, Mentzer RM, Murphy E, Ovize M, Ping P, Przyklenk K, Sack MN, Vander Heide RS, Vinten-Johansen J, Yellon DM (2011) New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop. Circulation 124:1172–1179. doi:10.1161/CIRCULATIONAHA.111.032698

    Article  Google Scholar 

  30. Siami S, Bailly-Salin J, Polito A, Porcher R, Blanchard A, Haymann JP, Laborde K, Maxime V, Boucly C, Carlier R, Annane D, Sharshar T (2010) Osmoregulation of vasopressin secretion is altered in the postacute phase of septic shock. Crit Care Med 38:1962–1969. doi:10.1097/CCM.0b013e3181eb9acf

    PubMed  CAS  Google Scholar 

  31. Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, Jakob H, Heusch G (2010) Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol 105:657–664. doi:10.1007/s00395-010-0104-5

    Article  PubMed  CAS  Google Scholar 

  32. Venugopal V, Hausenloy DJ, Ludman A, Di Salvo C, Kolvekar S, Yap J, Lawrence D, Bognolo J, Yellon DM (2009) Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial. Heart 95:1567–1571. doi:10.1136/hrt.2008.155770

    Article  PubMed  CAS  Google Scholar 

  33. Venugopal V, Laing CM, Ludman A, Yellon DM, Hausenloy D (2010) Effect of remote ischemic preconditioning on acute kidney injury in nondiabetic patients undergoing coronary artery bypass graft surgery: a secondary analysis of 2 small randomized trials. Am J Kidney Dis 56:1043–1049. doi:10.1053/j.ajkd.2010.07.014

    Article  PubMed  Google Scholar 

  34. Vermes E, Mesguich M, Houel R, Soustelle C, Le Besnerais P, Hillion ML, Loisance D (2000) Cardiac troponin I release after open heart surgery: a marker of myocardial protection? Ann Thorac Surg 70:2087–2090

    Article  PubMed  CAS  Google Scholar 

  35. Wagner R, Piler P, Bedanova H, Adamek P, Grodecka L, Freiberger T (2010) Myocardial injury is decreased by late remote ischaemic preconditioning and aggravated by tramadol in patients undergoing cardiac surgery: a randomised controlled trial. Interact Cardiovasc Thorac Surg 11:758–762. doi:10.1510/icvts.2010.243600

    Article  PubMed  Google Scholar 

  36. Xie JJ, Liao XL, Chen WG, Huang DD, Chang FJ, Chen W, Luo ZL, Wang ZP, Ou JS (2011) Remote ischaemic preconditioning reduces myocardial injury in patients undergoing heart valve surgery: randomised controlled trial. Heart. doi:10.1136/heartjnl-2011-300860

    Google Scholar 

  37. Zimmerman RF, Ezeanuna PU, Kane JC, Cleland CD, Kempananjappa TJ, Lucas FL, Kramer RS (2011) Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery. Kidney Int 80:861–867. doi:10.1038/ki.2011.156

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was funded by unrestricted grants from the New Zealand Lotteries Commission and the National Heart Foundation of New Zealand.

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Authors and Affiliations

  1. Wellington Hospital, Capital and Coast District Health Board, Private Bag 7902, Wellington, 6242, New Zealand

    Paul Jeffrey Young, Paul Dalley, Alexander Garden, Christopher Horrocks, Barry Mahon, William Young & Richard Beasley

  2. Medical Research Institute of New Zealand, Private Bag 7902, Wellington, 6242, New Zealand

    Paul Jeffrey Young, Janine Pilcher, Mark Weatherall & Richard Beasley

  3. School of Biological Sciences, Victoria University of Wellington, PO Box 600, Wellington, 6140, New Zealand

    Alexander Garden, Anne La Flamme, John Miller & Jenni Williams

  4. University of Otago, Wellington, PO Box 7343, Wellington South, Wellington, 6021, New Zealand

    Mark Weatherall

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Correspondence to Paul Jeffrey Young.

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To this article two Invited Editorials are available at doi:10.1007/s00395-012-0258-4 and doi:10.1007/s00395-012-0259-3.

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Young, P.J., Dalley, P., Garden, A. 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, 256 (2012). https://doi.org/10.1007/s00395-012-0256-6

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