Skip to main content
Top
Published in: Basic Research in Cardiology 3/2012

01-05-2012 | Original Contribution

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

Authors: Paul Jeffrey Young, Paul Dalley, Alexander Garden, Christopher Horrocks, Anne La Flamme, Barry Mahon, John Miller, Janine Pilcher, Mark Weatherall, Jenni Williams, William Young, Richard Beasley

Published in: Basic Research in Cardiology | Issue 3/2012

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
2.
go back to reference 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 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
3.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
4.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
5.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
6.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
7.
go back to reference 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 PubMedCrossRef 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/​S026502150800382​7 PubMedCrossRef
8.
go back to reference Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–2200PubMed Gho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD (1996) Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193–2200PubMed
9.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
10.
go back to reference 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 97:33–41PubMedCrossRef 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 97:33–41PubMedCrossRef
11.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
12.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
14.
go back to reference 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 38:924–929PubMed 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 38:924–929PubMed
15.
go back to reference Hu ZY, Liu J (2009) Mechanism of cardiac preconditioning with volatile anaesthetics. Anaesth Intensive Care 37:532–538PubMed Hu ZY, Liu J (2009) Mechanism of cardiac preconditioning with volatile anaesthetics. Anaesth Intensive Care 37:532–538PubMed
16.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
17.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
18.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
19.
go back to reference 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 105:503–510PubMedCrossRef 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 105:503–510PubMedCrossRef
25.
go back to reference Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B (1997) Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol 273:H1707–H1712PubMed Oxman T, Arad M, Klein R, Avazov N, Rabinowitz B (1997) Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am J Physiol 273:H1707–H1712PubMed
27.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
28.
go back to reference 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 78:1100–1104PubMed 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 78:1100–1104PubMed
29.
go back to reference 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 CrossRef 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 CrossRef
30.
go back to reference 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 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
31.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
32.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
33.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
34.
go back to reference 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 70:2087–2090PubMedCrossRef 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 70:2087–2090PubMedCrossRef
35.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
36.
go back to reference 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 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
37.
go back to reference 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 PubMedCrossRef 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 PubMedCrossRef
Metadata
Title
A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol
Authors
Paul Jeffrey Young
Paul Dalley
Alexander Garden
Christopher Horrocks
Anne La Flamme
Barry Mahon
John Miller
Janine Pilcher
Mark Weatherall
Jenni Williams
William Young
Richard Beasley
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Basic Research in Cardiology / Issue 3/2012
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-012-0256-6

Other articles of this Issue 3/2012

Basic Research in Cardiology 3/2012 Go to the issue