The remote ischemic preconditioning algorithm: effect of number of cycles, cycle duration and effector organ mass on efficacy of protection

  • Jacob JohnsenEmail author
  • Kasper Pryds
  • Rasha Salman
  • Bo Løfgren
  • Steen Buus Kristiansen
  • Hans Erik Bøtker
Original Contribution


Remote ischemic preconditioning (rIPC), induced by cycles of transient limb ischemia and reperfusion (IR), is cardioprotective. The optimal rIPC-algorithm is not established. We investigated the effect of cycle numbers and ischemia duration within each rIPC-cycle and the influence of effector organ mass on the efficacy of cardioprotection. Furthermore, the duration of the early phase of protection by rIPC was investigated. Using a tourniquet tightened at the inguinal level, we subjected C57Bl/6NTac mice to intermittent hind-limb ischemia and reperfusion. The rIPC-protocols consisted of (I) two, four, six or eight cycles, (II) 2, 5 or 10 min of ischemia in each cycle, (III) single or two hind-limb occlusions and (IV) 0.5, 1.5, 2.0 or 2.5 h intervals from rIPC to index cardiac ischemia. All rIPC algorithms were followed by 5 min of reperfusion. The hearts were subsequently exposed to 25 min of global ischemia and 60 min of reperfusion in an ex vivo Langendorff model. Cardioprotection was evaluated by infarct size and post-ischemic hemodynamic recovery. Four to six rIPC cycles yielded significant cardioprotection with no further protection by eight cycles. Ischemic cycles lasting 2 min offered the same protection as cycles of 5 min ischemia, whereas prolonged cycles lasting 10 min abrogated protection. One and two hind-limb preconditioning were equally protective. In our mouse model, the duration of protection by rIPC was 1.5 h. These findings indicate that the number and duration of cycles rather than the tissue mass exposed to rIPC determines the efficacy of rIPC.


Cardioprotection Ischemia–reperfusion Remote ischemic conditioning Preconditioning Infarct size 



We thank Casper Carlsen Elkjær and Anja Helveg Larsen for excellent technical assistance. This study was supported financially by the Danish Heart Foundation, The Danish Strategic Research Council (11-1115818), The Beckett Foundation and the Institute of Clinical Medicine, Aarhus University.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    Bøtker HE, Kharbanda R, Schmidt MR, Bøttcher 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, Sørensen 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 CrossRefPubMedGoogle Scholar
  2. 2.
    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 CrossRefPubMedGoogle Scholar
  3. 3.
    Kharbanda RK, Mortensen UM, White PA, Kristiansen SB, Schmidt MR, Hoschtitzky JA, Vogel M, Sorensen K, Redington AN, MacAllister R (2002) Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 106:2881–2883. doi: 10.1161/01.cir.0000043806.51912.9b CrossRefPubMedGoogle Scholar
  4. 4.
    Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P (1993) Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87:893–899. doi: 10.1161/01.cir.87.3.893 CrossRefPubMedGoogle Scholar
  5. 5.
    Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D (2015) Remote ischemic conditioning. J Am Coll Cardiol 65:177–195. doi: 10.1016/j.jacc.2014.10.031 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ovize M, Thibault H, Przyklenk K (2013) Myocardial conditioning: opportunities for clinical translation. Circ Res 113:439–450. doi: 10.1161/CIRCRESAHA.113.300764 CrossRefPubMedGoogle Scholar
  7. 7.
    Przyklenk K, Whittaker P (2013) Genesis of remote conditioning: action at a distance–’hypotheses non fingo’? J Cardiovasc Med Hagerstown 14:180–186. doi: 10.2459/JCM.0b013e328358c8eb CrossRefPubMedGoogle Scholar
  8. 8.
    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 CrossRefPubMedGoogle Scholar
  9. 9.
    Hong DM, Lee EH, Kim HJ, Min JJ, Chin JH, Choi DK, Bahk JH, Sim JY, Choi IC, Jeon Y (2014) Does remote ischaemic preconditioning with postconditioning improve clinical outcomes of patients undergoing cardiac surgery? Remote ischaemic preconditioning with postconditioning outcome trial. Eur Heart J 35:176–183. doi: 10.1093/eurheartj/eht346 CrossRefPubMedGoogle Scholar
  10. 10.
    Prasad A, Gossl M, Hoyt J, Lennon RJ, Polk L, Simari R, Holmes DR Jr, Rihal CS, Lerman A (2013) Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: a single center randomized sham controlled trial. Catheter Cardiovasc Interv 81:930–936. doi: 10.1002/ccd.24443 CrossRefPubMedGoogle Scholar
  11. 11.
    Iliodromitis EK, Kyrzopoulos S, Paraskevaidis IA, Kolocassides KG, Adamopoulos S, Karavolias G, Kremastinos DT (2006) Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart 92:1821–1826. doi: 10.1136/hrt.2006.089060 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hausenloy DJ, Yellon DM (2012) “Conditional conditioning” in cardiac bypass surgery. Basic Res Cardiol 107:258. doi: 10.1007/s00395-012-0258-4 CrossRefPubMedGoogle Scholar
  13. 13.
    Przyklenk K (2013) Reduction of myocardial infarct size with ischemic “conditioning”: physiologic and technical considerations. Anesth Analg 117:891–901. doi: 10.1213/ANE.0b013e318294fc63 CrossRefPubMedGoogle Scholar
  14. 14.
    Przyklenk K, Whittaker P (2011) Remote ischemic preconditioning: current knowledge, unresolved questions, and future priorities. J Cardiovasc Pharmacol Ther 16:255–259. doi: 10.1177/1074248411409040 CrossRefPubMedGoogle Scholar
  15. 15.
    Whittaker P, Przyklenk K (2014) From ischemic conditioning to ‘hyperconditioning’: clinical phenomenon and basic science opportunity. Dose Response 12:650–663. doi: 10.2203/dose-response.14-035.Whittaker CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Li GC, Vasquez JA, Gallagher KP, Lucchesi BR (1990) Myocardial protection with preconditioning. Circulation 82:609–619. doi: 10.1161/01.cir.82.2.609 CrossRefPubMedGoogle Scholar
  17. 17.
    Goto M, Liu Y, Yang XM, Ardell JL, Cohen MV, Downey JM (1995) Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res 77:611–621. doi: 10.1161/01.res.77.3.611 CrossRefPubMedGoogle Scholar
  18. 18.
    Sandhu R, Diaz RJ, Mao GD, Wilson GJ (1997) Ischemic preconditioning: differences in protection and susceptibility to blockade with single-cycle versus multicycle transient ischemia. Circulation 96:984–995. doi: 10.1161/01.CIR.96.3.984 CrossRefPubMedGoogle Scholar
  19. 19.
    Cohen MV, Yang XM, Downey JM (1994) Conscious rabbits become tolerant to multiple episodes of ischemic preconditioning. Circ Res 74:998–1004. doi: 10.1161/01.RES.74.5.998 CrossRefPubMedGoogle Scholar
  20. 20.
    Iliodromitis EK, Kremastinos DT, Katritsis DG, Papadopoulos CC, Hearse DJ (1997) Multiple cycles of preconditioning cause loss of protection in open-chest rabbits. J Mol Cell Cardiol 29:915–920. doi: 10.1006/jmcc.1996.0328 CrossRefPubMedGoogle Scholar
  21. 21.
    Xin P, Zhu W, Li J, Ma S, Wang L, Liu M, Li J, Wei M, Redington AN (2010) Combined local ischemic postconditioning and remote perconditioning recapitulate cardioprotective effects of local ischemic preconditioning. Am J Physiol Heart Circ Physiol 298:H1819–H1831. doi: 10.1152/ajpheart.01102.2009 CrossRefPubMedGoogle Scholar
  22. 22.
    Lu Y, Dong CS, Yu JM, Li H (2012) Morphine reduces the threshold of remote ischemic preconditioning against myocardial ischemia and reperfusion injury in rats: the role of opioid receptors. J Cardiothorac Vasc Anesth 26:403–406. doi: 10.1053/j.jvca.2011.07.036 CrossRefPubMedGoogle Scholar
  23. 23.
    Zografos TA, Katritsis GD, Tsiafoutis I, Bourboulis N, Katsivas A, Katritsis DG (2014) Effect of one-cycle remote ischemic preconditioning to reduce myocardial injury during percutaneous coronary intervention. Am J Cardiol 113:2013–2017. doi: 10.1016/j.amjcard.2014.03.043 CrossRefPubMedGoogle Scholar
  24. 24.
    Schulz R, Post H, Vahlhaus C, Heusch G (1998) Ischemic preconditioning in pigs: a graded phenomenon: its relation to adenosine and bradykinin. Circulation 98:1022–1029. doi: 10.1161/01.cir.98.10.1022 CrossRefPubMedGoogle Scholar
  25. 25.
    Yamakawa K, Zhou W, Ko Y, Benharash P, Takemoto M, Mahajan A (2014) Improved cardioprotection using a novel stepwise ischemic preconditioning protocol in rabbit heart. J Surg Res 188:381–386. doi: 10.1016/j.jss.2014.01.016 CrossRefPubMedGoogle Scholar
  26. 26.
    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. doi: 10.1161/01.CIR.94.9.2193 CrossRefPubMedGoogle Scholar
  27. 27.
    Basalay M, Barsukevich V, Mastitskaya S, Mrochek A, Pernow J, Sjoquist PO, Ackland GL, Gourine AV, Gourine A (2012) Remote ischaemic pre- and delayed postconditioning—similar degree of cardioprotection but distinct mechanisms. Exp Physiol 97:908–917. doi: 10.1113/expphysiol.2012.064923 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chen YS, Chien CT, Ma MC, Tseng YZ, Lin FY, Wang SS, Chen CF (2005) Protection “outside the box” (skeletal remote preconditioning) in rat model is triggered by free radical pathway. J Surg Res 126:92–101. doi: 10.1016/j.jss.2005.01.007 CrossRefPubMedGoogle Scholar
  29. 29.
    Grall S, Prunier-Mirebeau D, Tamareille S, Mateus V, Lamon D, Furber A, Prunier F (2013) Endoplasmic reticulum stress pathway involvement in local and remote myocardial ischemic conditioning. Shock 39:433–439. doi: 10.1097/SHK.0b013e31828e4f80 CrossRefPubMedGoogle Scholar
  30. 30.
    Shahid M, Tauseef M, Sharma KK, Fahim M (2008) Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms. Exp Physiol 93:954–968. doi: 10.1113/expphysiol.2007.041442 CrossRefPubMedGoogle Scholar
  31. 31.
    Tamareille S, Mateus V, Ghaboura N, Jeanneteau J, Croue A, Henrion D, Furber A, Prunier F (2011) RISK and SAFE signaling pathway interactions in remote limb ischemic perconditioning in combination with local ischemic postconditioning. Basic Res Cardiol 106:1329–1339. doi: 10.1007/s00395-011-0210-z CrossRefPubMedGoogle Scholar
  32. 32.
    Loukogeorgakis SP, Williams R, Panagiotidou AT, Kolvekar SK, Donald A, Cole TJ, Yellon DM, Deanfield JE, MacAllister RJ (2007) Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism. Circulation 116:1386–1395. doi: 10.1161/CIRCULATIONAHA.106.653782 CrossRefPubMedGoogle Scholar
  33. 33.
    Wu Q, Gui P, Wu J, Ding D, Purusram G, Dong N, Yao S (2011) Effect of limb ischemic preconditioning on myocardial injury in patients undergoing mitral valve replacement surgery—a randomized controlled trial. Circ J 75:1885–1889. doi: 10.1253/circj.CJ-10-1130 CrossRefPubMedGoogle Scholar
  34. 34.
    Dirnagl U, Becker K, Meisel A (2009) Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol 8:398–412. doi: 10.1016/S1474-4422(09)70054-7 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Hausenloy DJ, Yellon DM (2010) The second window of preconditioning (SWOP) where are we now? Cardiovasc Drugs Ther 24:235–254. doi: 10.1007/s10557-010-6237-9 CrossRefPubMedGoogle Scholar
  36. 36.
    Saxena P, Newman MA, Shehatha JS, Redington AN, Konstantinov IE (2010) Remote ischemic conditioning: evolution of the concept, mechanisms, and clinical application. J Card Surg 25:127–134. doi: 10.1111/j.1540-8191.2009.00820.x CrossRefPubMedGoogle Scholar
  37. 37.
    Burckhartt B, Yang XM, Tsuchida A, Mullane KM, Downey JM, Cohen MV (1995) Acadesine extends the window of protection afforded by ischaemic preconditioning in conscious rabbits. Cardiovasc Res 29:653–657. doi: 10.1016/0008-6363(96)88636-6 CrossRefPubMedGoogle Scholar
  38. 38.
    Ghosh S, Standen NB, Galinanes M (2000) Preconditioning the human myocardium by simulated ischemia: studies on the early and delayed protection. Cardiovasc Res 45:339–350. doi: 10.1016/s0008-6363(99)00353-3 CrossRefPubMedGoogle Scholar
  39. 39.
    Murry CE, Richard VJ, Jennings RB, Reimer KA (1991) Myocardial protection is lost before contractile function recovers from ischemic preconditioning. Am J Physiol 260:H796–H804PubMedGoogle Scholar
  40. 40.
    Sack S, Mohri M, Arras M, Schwarz ER, Schaper W (1993) Ischaemic preconditioning—time course of renewal in the pig. Cardiovasc Res 27:551–555. doi: 10.1093/cvr/27.4.551 CrossRefPubMedGoogle Scholar
  41. 41.
    Van Winkle DM, Thornton JD, Downey DM, Downey JM (1991) The natural history of preconditioning: cardioprotection depends on duration of transient ischemia and time to subsequent ischemia. Coron Artery Dis 2:613–619Google Scholar
  42. 42.
    Weber NC, Riedemann I, Smit KF, Zitta K, van de Vondervoort D, Zuurbier CJ, Hollmann MW, Preckel B, Albrecht M (2015) Plasma from human volunteers subjected to remote ischemic preconditioning protects human endothelial cells from hypoxia-induced cell damage. Basic Res Cardiol 110:17. doi: 10.1007/s00395-015-0474-9 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    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 CrossRefPubMedGoogle Scholar
  44. 44.
    Rassaf T, Totzeck M, Hendgen-Cotta UB, Shiva S, Heusch G, Kelm M (2014) Circulating nitrite contributes to cardioprotection by remote ischemic preconditioning. Circ Res 114:1601–1610. doi: 10.1161/CIRCRESAHA.114.303822 CrossRefPubMedGoogle Scholar
  45. 45.
    Davidson SM, Selvaraj P, He D, Boi-Doku C, Yellon RL, Vicencio JM, Yellon DM (2013) Remote ischaemic preconditioning involves signalling through the SDF-1alpha/CXCR4 signalling axis. Basic Res Cardiol 108:377. doi: 10.1007/s00395-013-0377-6 CrossRefPubMedGoogle Scholar
  46. 46.
    Schulz R, Gres P, Heusch G (2001) Role of endogenous opioids in ischemic preconditioning but not in short-term hibernation in pigs. Am J Physiol Heart Circ Physiol 280:H2175–H2181PubMedGoogle Scholar
  47. 47.
    Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G (2015) Across-species transfer of protection by remote ischemic preconditioning with species-specific myocardial signal transduction by reperfusion injury salvage kinase and survival activating factor enhancement pathways. Circ Res 117:279–288. doi: 10.1161/CIRCRESAHA.117.306878 CrossRefPubMedGoogle Scholar
  48. 48.
    Li J, Rohailla S, Gelber N, Rutka J, Sabah N, Gladstone RA, Wei C, Hu P, Kharbanda RK, Redington AN (2014) MicroRNA-144 is a circulating effector of remote ischemic preconditioning. Basic Res Cardiol 109:423. doi: 10.1007/s00395-014-0423-z CrossRefPubMedGoogle Scholar
  49. 49.
    Kalakech H, Tamareille S, Pons S, Godin-Ribuot D, Carmeliet P, Furber A, Martin V, Berdeaux A, Ghaleh B, Prunier F (2013) Role of hypoxia inducible factor-1alpha in remote limb ischemic preconditioning. J Mol Cell Cardiol 65:98–104. doi: 10.1016/j.yjmcc.2013.10.001 CrossRefPubMedGoogle Scholar
  50. 50.
    Wong GT, Lu Y, Mei B, Xia Z, Irwin MG (2012) Cardioprotection from remote preconditioning involves spinal opioid receptor activation. Life Sci 91:860–865. doi: 10.1016/j.lfs.2012.08.037 CrossRefPubMedGoogle Scholar
  51. 51.
    Schmidt MR, Stottrup NB, Michelsen MM, Contractor H, Sorensen KE, Kharbanda RK, Redington AN, Botker HE (2014) Remote ischemic preconditioning impairs ventricular function and increases infarct size after prolonged ischemia in the isolated neonatal rabbit heart. J Thorac Cardiovasc Surg 147:1049–1055. doi: 10.1016/j.jtcvs.2013.05.022 CrossRefPubMedGoogle Scholar
  52. 52.
    Veighey K, Macallister RJ (2012) Clinical applications of remote ischemic preconditioning. Cardiol Res Pract 2012:620681. doi: 10.1155/2012/620681 PubMedPubMedCentralGoogle Scholar
  53. 53.
    Jensen RV, Zachara NE, Nielsen PH, Kimose HH, Kristiansen SB, Botker HE (2013) Impact of O-GlcNAc on cardioprotection by remote ischaemic preconditioning in non-diabetic and diabetic patients. Cardiovasc Res 97:369–378. doi: 10.1093/cvr/cvs337 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson S, Xenou M, Clayton T, Yellon DM, Investigators ET (2015) Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med. doi: 10.1056/NEJMoa1413534 Google Scholar
  55. 55.
    Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B, Roesner J, Kletzin F, Strouhal U, Reyher C, Laufenberg-Feldmann R, Ferner M, Brandes IF, Bauer M, Stehr SN, Kortgen A, Wittmann M, Baumgarten G, Meyer-Treschan T, Kienbaum P, Heringlake M, Schon J, Sander M, Treskatsch S, Smul T, Wolwender E, Schilling T, Fuernau G, Hasenclever D, Zacharowski K, Collaborators RIS (2015) A multicenter trial of remote ischemic preconditioning for heart surgery. N Engl J Med. doi: 10.1056/NEJMoa1413579 PubMedGoogle Scholar
  56. 56.
    Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhauser M, Peters J, Jakob H, Heusch G (2013) Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 382:597–604. doi: 10.1016/S0140-6736(13)61450-6 CrossRefPubMedGoogle Scholar
  57. 57.
    Zaugg M, Lucchinetti E (2015) Remote ischemic preconditioning in cardiac surgery—ineffective and risky? N Engl J Med. doi: 10.1056/NEJMe1510338 PubMedGoogle Scholar
  58. 58.
    Eitel I, Stiermaier T, Rommel KP, Fuernau G, Sandri M, Mangner N, Linke A, Erbs S, Lurz P, Boudriot E, Mende M, Desch S, Schuler G, Thiele H (2015) Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. Eur Heart J 36:3049–3057. doi: 10.1093/eurheartj/ehv463 CrossRefPubMedGoogle Scholar
  59. 59.
    Rentoukas I, Giannopoulos G, Kaoukis A, Kossyvakis C, Raisakis K, Driva M, Panagopoulou V, Tsarouchas K, Vavetsi S, Pyrgakis V, Deftereos S (2010) Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc Interv 3:49–55. doi: 10.1016/j.jcin.2009.10.015 CrossRefPubMedGoogle Scholar
  60. 60.
    Yellon DM, Ackbarkhan AK, Balgobin V, Bulluck H, Deelchand A, Dhuny MR, Domah N, Gaoneadry D, Jagessur RK, Joonas N, Kowlessur S, Lutchoo J, Nicholas JM, Pauvaday K, Shamloll O, Walker JM, Hausenloy DJ (2015) Remote ischemic conditioning reduces myocardial infarct size in STEMI patients treated by thrombolysis. J Am Coll Cardiol 65:2764–2765. doi: 10.1016/j.jacc.2015.02.082 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Jacob Johnsen
    • 1
    • 2
    Email author
  • Kasper Pryds
    • 1
    • 2
  • Rasha Salman
    • 1
    • 2
  • Bo Løfgren
    • 1
    • 2
  • Steen Buus Kristiansen
    • 1
    • 2
  • Hans Erik Bøtker
    • 1
    • 2
  1. 1.Department of CardiologyAarhus University HospitalAarhus NDenmark
  2. 2.Department of Clinical MedicineAarhus UniversityAarhusDenmark

Personalised recommendations