Myocardial remote ischemic preconditioning: From pathophysiology to clinical application;Pré-condicionamento isquémico remoto do miocárdio: Dosmecanismos fisiopatológicos à aplicacão na prática clínica

Revista Portuguesa de Cardiologia

Volumn 32, Issue 11, 2013, Pages 893-904

  Costa, José F ^a   Fontes Carvalho, Ricardo ^a,b   Leite Moreira, Adelino F ^a,c  

^a University of Porto   (Portugal)

^b CENTRO HOSPITALAR DE VILA NOVA DE GAIA ESPINHO   (Portugal)

^c Centro Hospitalar Universitário de São João   (Portugal)

Author keywords

Myocardial infarction; Myocardial ischemia; Myocardial ischemicpreconditioning; Myocardialreperfusion injury

Indexed keywords

ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; MITOCHONDRIAL PERMEABILITY TRANSITION PORE;

ABDOMINAL AORTA ANEURYSM; ARTICLE; CELL DEATH; CLINICAL PRACTICE; CLINICAL TRIAL (TOPIC); CORONARY ARTERY BLOOD FLOW; CORONARY ARTERY BYPASS SURGERY; HEART MUSCLE; HEART MUSCLE BLOOD FLOW; HEART MUSCLE ISCHEMIA; HEART MUSCLE REPERFUSION; HEART PROTECTION; HEART VALVE REPLACEMENT; HUMAN; ISCHEMIC PRECONDITIONING; PATHOPHYSIOLOGY; PERCUTANEOUS CORONARY INTERVENTION; CARDIAC MUSCLE; HEART; HEART INFARCTION PREVENTION; HEART SURGERY; METABOLISM; PROCEDURES; SKELETAL MUSCLE; VASCULARIZATION;

CARDIAC SURGICAL PROCEDURES; HEART; HUMANS; ISCHEMIC PRECONDITIONING, MYOCARDIAL; MUSCLE, SKELETAL; MYOCARDIUM; PERCUTANEOUS CORONARY INTERVENTION;

EID: 84893647059     PISSN: 08702551     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.repc.2013.02.012     Document Type: Short Survey

References (100)

1. de Luca G, Suryapranata H, Ottervanger JP, et al. Time delay to treatment and mortality in primary angioplasty for acute myo-cardial infarction: Every minute of delay counts. Circulation.2004;109:1223-5. (Pubitemid 38372780)
2. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190:255-66. (Pubitemid 30141372)
3. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N EnglJ Med. 2007;357:1121-35.
4. Cleveland Jr JC, Meldrum DR, Cain BS, et al. Oral sulfonylurea hypoglycemic agents prevent ischemic preconditioning inhuman myocardium. Circulation. 1997;96:29-32. (Pubitemid 27298399)
5. Loubani M, Fowler A, Standen NB, et al. The effect of gli-clazide and glibenclamide on preconditioning of the humanmyocardium. Eur J Pharmacol. 2005;515:142-9. (Pubitemid 40779279)
6. Kottenberg E, Thielmann M, Bergmann L, et al. Protectionby remote ischemic preconditioning during coronary arterybypass graft surgery with isoflurane but not propofol - A clinicaltrial. Acta Anaesthesiol Scand. 2012;56:30-8.
7. Toller WG, Kersten JR, Pagel PS, et al. Sevoflurane reduces myocardial infarct size and decreases the time threshold for ischemic preconditioning in dogs. Anesthesiology.1999;91:1437-46. (Pubitemid 29506108)
8. Pilcher JM, Young P, Weatherall M, et al. A systematic reviewand meta-analysis of the cardio protective effects of remoteischaemic preconditioning in open cardiac surgery. J R Soc Med. 2012;105:436-45.
9. d'Ascenzo F, Cavallero E, Moretti C, et al. Remote ischaemicpre conditioning in coronary artery bypass surgery: A meta-analysis. Heart. 2012;98:1267-71.
10. Meybohm P, Zacharowski K, Cremer J, et al. Remote ischaemicpre conditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial-the RIP Heart-Study. Eur Heart J. 2012;33:1423-6.
11. Deja MA, Golba KS, Malinowski M, et al. Diazoxide provi-des maximal KATP channels independent protection if present throughout hypoxia. Ann Thorac Surg. 2006;81:1408-16.
12. Deja MA, Malinowski M, Golba KS, et al. Diazoxide protectsmyocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia. J Thorac CardiovascSurg. 2009;137:997-1004, e1-2.
13. IONA Study Group. Effect of nicorandil on coronary events inpatients with stable angina: The Impact Of Nicorandil in Angina(IONA) randomised trial. Lancet. 2002;359:1269-75.
14. Horinaka S. Use of nicorandil in cardiovascular disease and itsoptimization. Drugs. 2011;71:1105-19.
15. Wood KJ, Goto R. Mechanisms of rejection: Current perspec-tives. Transplantation. 2012;93:1-10.
16. Botker HE, Kharbanda R, Schmidt MR, et al. Remote ischae-mic conditioning before hospital admission, as a complementto angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: A randomised trial. Lancet.2010;375:727-34.
17. Abu-Amara M, Yang SY, Quaglia A, et al. Nitric oxideis an essential mediator of the protective effects of remote ischaemic preconditioning in a mouse model ofliver ischaemia/reperfusion injury. Clin Sci (Lond). 2011;121:257-66.
18. Avgerinos ED, Kostopanagiotou G, Costopanagiotou C, et al.Intestinal preconditioning ameliorates ischemia-reperfusioninduced acute lung injury in rats: An experimental study.J Surg Res. 2010;160:294-301.
19. Takaoka A, Nakae I, Mitsunami K, et al. Renal ische-mia/reperfusion remotely improves myocardial energy meta-bolism during myocardial ischemia via adenosine receptors inrabbits: Effects of "remote preconditioning". J Am Coll Car-diol. 1999;33:556-64. (Pubitemid 29234221)
20. Pell TJ, Baxter GF, Yellon DM, et al. Renal ischemia pre-conditions myocardium: Role of adenosine receptors andATP-sensitive potassium channels. Am J Physiol. 1998;275 5Pt 2:H1542-7.
21. Liem DA, Verdouw PD, Ploeg H, et al. Sites of action of adeno-sine in interorgan preconditioning of the heart. Am J PhysiolHeart Circ Physiol. 2002;283:H29-37. (Pubitemid 34705320)
22. Ding YF, Zhang MM, He RR. Role of renal nerve incardioprotection provided by renal ischemic preconditio-ning in anesthetized rabbits. Sheng Li Xue Bao. 2001;53:7-12.
23. Schoemaker RG, van Heijningen CL. Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol. 2000;278:H1571-6.
24. Wolfrum S, Schneider K, Heidbreder M, et al. Remote pre-conditioning protects the heart by activating myocardialPKCepsilon-isoform. Cardiovasc Res. 2002;55:583-9. (Pubitemid 34874954)
25. Wolfrum S, Nienstedt J, Heidbreder M, et al. Calcitonin generelated peptide mediates cardioprotection by remote precon-ditioning. Regul Pept. 2005;127:217-24. (Pubitemid 40179259)
26. Xiao L, Lu R, Hu CP, et al. Delayed cardio protection by intestinal preconditioning is mediated by calcitonin gene-related peptide. Eur J Pharmacol. 2001;427:131-5. (Pubitemid 32835295)
27. Tang ZL, Dai W, Li YJ, et al. Involvement of capsaicin-sensitive sensory nerves in early and delayed cardio protection inducedby a brief ischaemia of the small intestine. Naunyn Schmiede-bergs Arch Pharmacol. 1999;359:243-7. (Pubitemid 29142876)
28. Dickson EW, Tubbs RJ, Porcaro WA, et al. Myocardial precondi-tioning factors evoke mesenteric ischemic tolerance via opioidreceptors and K(ATP) channels. Am J Physiol Heart Circ Physiol.2002;283:H22-H8.
29. Patel HH, Moore J, Hsu AK, et al. Cardio protection at adistance: Mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism. J Mol Cell Cardiol.2002;34:1317-23. (Pubitemid 35244409)
30. Zhang SZ, Wang NF, Xu J, et al. Kappa-opioid receptors mediate cardioprotection by remote preconditioning. Anesthesiology.2006;105:550-6. (Pubitemid 44310438)
31. Weinbrenner C, Schulze F, Sarvary L, et al. Remote pre-conditioning by in frarenal aortic occlusion is operative viadelta1-opioid receptors and free radicals in vivo in the ratheart. Cardiovasc Res. 2004;61:591-9. (Pubitemid 38210164)
32. Wong GT, Lu Y, Mei B, et al. Cardio protection from remote preconditioning involves spinal opioid receptor activation. Life Sci. 2012;91:860-5.
33. Ali ZA, Callaghan CJ, Lim E, et al. Remote ischemic preconditioning reduces myocardial and renal injuryafter elective abdominal aortic aneurysm repair: A randomized controlled trial. Circulation. 2007;116 11 Suppl:I98-105.
34. Hoole SP, Heck PM, Sharples L, et al. Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent)Study: A prospective, randomized control trial. Circulation.2009;119:820-7.
35. Li L, Luo W, Huang L, et al. Remote per conditioning reduce smyocardial injury in adult valve replacement: A randomizedcontrolled trial. J Surg Res. 2010;164: e2-e6.
36. Thielmann M, Kottenberg E, Boengler K, et al. Remote ischemic preconditioning reduces myocardial injury after coronaryartery bypass surgery with crystalloid cardioplegic arrest.Basic Res Cardiol. 2010;105:657-64.
37. Rahman IA, Mascaro JG, Steeds RP, et al. Remote ischemic preconditioning in human coronary artery bypass surgery: From promise to disappointment Circulation. 2010;122 11Suppl: S53-9.
38. Karuppasamy P, Chaubey S, Dew T, et al. Remote intermit-tent ischemia before coronary artery bypass graft surgery:A strategy to reduce injury and inflammation Basic Res Car-diol. 2011;106:511-9.
39. Venugopal V, Hausenloy DJ, Ludman A, et al. Remote ischa-emic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood car dioplegia:A randomised controlled trial. Heart. 2009;95:1567-71.
40. Ghaemian A, Nouraei SM, Abdollahian F, et al. Remote ischemic preconditioning in per cutaneous coronary revascularization:A double-blind randomized controlled clinical trial. Asian Car-diovasc Thorac Ann. 2012;20:548-54.
41. Prasad A, Gossl M, Hoyt J, et al. Remote ischemic pre conditoning immediately before percutaneous coronary inter vention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: A singlecenter randomized sham controlled trial. Catheter Car diovascInterv. 2013;81:930-6.
42. Lomivorotov VV, Shmyrev VA, Nepomnyaschih VA, 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.
43. Young PJ, Dalley P, Garden A, et al. A pilot study investiga-ting the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol. Basic Res Cardiol. 2012;107:256.
44. Murry CE, Jennings RB, Reimer KA. Preconditioning with ische-mia: A delay of lethal cell injury in ischemic myocardium.Circulation. 1986;74:1124-36. (Pubitemid 17174962)
45. Schmidt MR, Smerup M, Konstantinov IE, et al. Inter mitten peripheral tissue ischemia during coronary ischemia reduce smyocar dial infarction through a KATP-dependent mechanism:First demonstration of remote ischemic perconditioning. Am JPhysiol Heart Circ Physiol. 2007;292:H1883-90.
46. Andreka G, Vertesaljai M, Szantho G, et al. Remote is chaemic post conditioning protects the heart during acute myocardialinfarction in pigs. Heart. 2007;93:749-52. (Pubitemid 46808282)
47. Przyklenk K, Bauer B, Ovize M, et al. Regional ischemic' reconditioning' protects remote virgin myocardium from sub-sequent sustained coronary occlusion. Circulation. 1993;87:893-9. (Pubitemid 23070821)
48. Gho BC, Schoemaker RG, van den Doel MA, et al. Myocardial protection by brief ischemia in non cardiac tissue. Circulation.1996;94:2193-200. (Pubitemid 26360513)
49. Walsh SR, Tang T, Sadat U, et al. Cardio protection by remote ischaemic preconditioning. Br J Anaesth. 2007;99:611-6. (Pubitemid 351773226)
50. Birnbaum Y, Hale SL, Kloner RA. Ischemic preconditioning Ata distance: Reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimula-tion of the gastrocnemius muscle in the rabbit. Circulation.1997;96:1641-6. (Pubitemid 27375364)
51. Oxman T, Arad M, Klein R, et al. Limb is chemia preconditionsthe heart against reperfusion tachyarrhythmia. Am J Physiol.1997;273 4 Pt 2:H1707-12.
52. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: A review. Cardiovasc Surg.2002;10:620-30. (Pubitemid 35365880)
53. Baxter GF, Goma FM, Yellon DM. Characterisation of the infarct-limiting effect of delayed preconditioning: Time course and dose-dependency studies in rabbit myocardium. Basic ResCardiol. 1997;92:159-67. (Pubitemid 27282973)
54. Loukogeorgakis SP, Panagiotidou AT, Broadhead MW, et al. 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;46:450-6. (Pubitemid 41040285)
55. Zhou K, Yang B, Zhou XM, et al. Effects of remote ischemic preconditioning on the flow pattern of the left anterior descending coronary artery in normal subjects. Int J Cardiol.2007;122:250-1. (Pubitemid 47615181)
56. Shimizu M, Konstantinov IE, Kharbanda RK, et al. Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs. Acta Physiol (Oxf).2007;190:103-9. (Pubitemid 46776393)
57. Dow J, Bhandari A, Simkhovich BZ, et al. The effect of acute versus delayed remote ischemic preconditioning on reperfusion induced ventricular arrhythmias. J Cardiovasc Electrophysiol. 2012.
58. Hajrasouliha AR, Tavakoli S, Ghasemi M, et al. Endogenous can-nabinoids contribute to remote ischemic preconditioning viacannabinoid CB2 receptors in the rat heart. Eur J Pharmacol.2008;579:246-52.
59. Kristiansen SB, Henning O, Kharbanda RK, et al. Remote pre-conditioning reduces ischemic injury in the explanted heartby a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol. 2005;288:H1252-6.
60. Li G, Labruto F, Sirsjo A, et al. Myocardial protection by remote preconditioning: The role of nuclear factor kappa-Bp105 and inducible nitric oxide synthase. Eur J CardiothoracSurg. 2004;26:968-73. (Pubitemid 39433881)
61. Konstantinov IE, Arab S, Li J, et al. The remote ischemicpre conditioning stimulus modifies gene expression in mousemyocardium. J Thorac Cardiovasc Surg. 2005;130:1326-32. (Pubitemid 41543201)
62. Konstantinov IE, Arab S, Kharbanda RK, et al. The remoteischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol Genomics. 2004;19:143-50. (Pubitemid 40039920)
63. Liem DA, te Lintel Hekkert M, Manintveld OC, et al. Myocardium tolerant to an adenosine-dependent ischemic pre-conditioning stimulus can still be protected by stimuli thatemploy alternative signaling pathways. Am J Physiol Heart CircPhysiol. 2005;288:H1165-72.
64. Chen XG, Wu BY, Wang JK, et al. Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury. Chin Med J (Engl).2005;118:1723-7.
65. Dong JH, Liu YX, Ji ES, et al. Limb ischemic pre conditioning reduces infarct size following myocardial ischemia-reperfusionin rats. Sheng Li Xue Bao. 2004;56:41-6.
66. Lim SY, Yellon DM, Hausenloy DJ. The neural and humoralpathways in remote limb ischemic preconditioning. Basic ResCardiol. 2010;105:651-5.
67. Mastitskaya S, Marina N, Gourine A, et al. Cardioprotec-tion evoked by remote ischaemic preconditioning is criticallydependent on the activity of vagal pre-ganglionic neurones.Cardiovasc Res. 2012;95:487-94.
68. Weinbrenner C, Nelles M, Herzog N, et al. Remote precon-ditioning by in frarenal occlusion of the aorta protects the heart from infarction: A newly identified non-neuronal but PKC-dependent pathway. Cardiovasc Res. 2002;55:590-601. (Pubitemid 34874955)
69. Konstantinov IE, Li J, Cheung MM, et al. Remote ische-mic preconditioning of the recipient reduces myocardialischemia-reperfusion injury of the denervated donor heartvia a Katp channel-dependent mechanism. Transplantation.2005;79:1691-5. (Pubitemid 40885266)
70. Shimizu M, Tropak M, Diaz RJ, et al. Transient limb ischaemiaremotely preconditions through a humoral mechanism actingdirectly on the myocardium: Evidence suggesting cross-speciesprotection. Clin Sci (Lond). 2009;117:191-200.
71. Shahid M, Tauseef M, Sharma KK, et al. Brief femoral arteryischaemia provides protection against myocardial ischaemia-reperfusion injury in rats: The possible mechanisms. Exp Physiol. 2008;93:954-68. (Pubitemid 352000273)
72. Ohnuma Y, Miura T, Miki T, et al. Opening of mitochondrialK(ATP) channel occurs downstream of PKC-epsilon activationin the mechanism of preconditioning. Am J Physiol Heart CircPhysiol. 2002;283:H440-H7.
73. Wang Y, Takashi E, Xu M, et al. Downregulation of proteinkinase C inhibits activation of mitochondrial K(ATP) channelsby diazoxide. Circulation. 2001;104:85-90. (Pubitemid 32623294)
74. Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. Physiol Rev.2008;88:581-609. (Pubitemid 351520088)
75. Heusch G, Boengler K, Schulz R. Inhibition of mitochondrial permeability transition pore opening: The Holy Grail of cardio protection. Basic Res Cardiol. 2010;105:151-4.
76. Murata M, Akao M, O'Rourke B, et al. Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overloadduring simulated ischemia and reperfusion: Possible mecha-nism of cardioprotection. Circ Res. 2001;89:891-8. (Pubitemid 34627894)
77. dos Santos P, Kowaltowski AJ, Laclau MN, et al. Mechanisms by which opening the mitochondrial ATP- sensitive K(+) channel protects the ischemic heart. Am J Physiol Heart Circ Physiol.2002;283:H284-95.
78. Vander Heide RS, Hill ML, Reimer KA, et al. Effect of reversible ischemia on the activity of the mitochondrial ATP ase:Relationship to ischemic preconditioning. J Mol Cell Cardiol.1996;28:103-12. (Pubitemid 26110456)
79. Ardehali H, O'Rourke B. Mitochondrial K(ATP) channels in cell survival and death. J Mol Cell Cardiol. 2005;39:7-16. (Pubitemid 40836042)
80. Chen YS, Chien CT, Ma MC, et al. Protection "outside the box"(skeletal remote preconditioning) in rat model is triggered by free radical pathway. J Surg Res. 2005;126:92-101.
81. Baines CP, Song CX, Zheng YT, et al. Protein kinase Cepsiloninteracts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res. 2003;92:873-80. (Pubitemid 36542528)
82. Ruiz-Meana M. Ischaemic preconditioning and mitochondrial permeability transition: A long-lasting relationship. Cardiovasc Res. 2012;96:157-9, discussion 60-4.
83. Hansen PR. Role of neutron phils in myocardial ischemia and reperfusion. Circulation. 1995;91:1872-85.
84. Kawata H, Yoshida K, Kawamoto A, et al. Ischemic preconditioning up regulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation ofprotein kinase C epsilon in the rat ischemic myocardium. Circ Res. 2001;88:696-704. (Pubitemid 32378139)
85. Frangogiannis NG. The immune system and cardiac repair.Pharmacol Res. 2008;58:88-111.
86. Kim YM, Kim TH, Seol DW, et al. Nitric oxide suppression of apoptosis occurs in association with an inhibitionof Bcl-2 cleavage and cytochrome c release. J Biol Chem.1998;273:31437-41.
87. Kim YM, Talanian RV, Li J, et al. Nitric oxide prevents IL-1beta and IFN-gamma-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1beta-convertingenzyme). J Immunol. 1998;161:4122-8. (Pubitemid 28468992)
88. Cheung MM, Kharbanda RK, Konstantinov IE, et al. Randomized controlled trial of the effects of remote is chemic preconditioning on children undergoing cardiac surgery: First clinical application in humans. J Am Coll Cardiol. 2006;47:2277-82. (Pubitemid 43795071)
89. Hausenloy DJ, Mwamure PK, Venugopal V, 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. (Pubitemid 47247853)
90. Fellahi JL, Gue X, Richomme X, et al. Short- And long-term prognostic value of postoperative cardiac troponin I concen-tration in patients undergoing coronary artery bypass grafting.Anesthesiology. 2003;99:270-4. (Pubitemid 36909551)
91. Kathiresan S, Servoss SJ, Newell JB, et al. Cardiac tro-ponin T elevation after coronary artery bypass grafting is associated with increased one-year mortality. Am J Cardiol.2004;94:879-81. (Pubitemid 39349551)
92. Steen H, Giannitsis E, Futterer S, et al. Cardiac troponinT at 96 hours after acute myocardial infarction correlates with infarct size and cardiac function. J Am Coll Cardiol.2006;48:2192-4. (Pubitemid 44855412)
93. Vasile VC, Babuin L, Giannitsis E, et al. Relationship of MRI-determined infarct size and cTnI measurements in patients with ST-elevation myocardial infarction. Clin Chem.2008;54:617-9. (Pubitemid 351348174)
94. 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 ischaemic preconditioning Heart. 2006;92:1821-6. (Pubitemid 44851332)
95. Hong DM, Mint JJ, Kim JH, 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.
96. Boengler K, Schulz R, Heusch G. Loss of cardioprotection withageing. Cardiovasc Res. 2009;83:247-61.
97. Hausenloy DJ, Baxter G, Bell R, et al. Translating novel strategies for cardio protection: The Hatter Workshop Recommendations. Basic Res Cardiol. 2010;105:677-86.
98. Lee TM, Su SF, Chou TF, et al. Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty. Circulation. 2002;105:334-40.
99. Jensen RV, Zachara NE, Nielsen PH, et al. Impact of O-GlcNAcon cardioprotection by remote ischaemic preconditioning in non-diabetic and diabetic patients. Cardiovasc Res. 2012.
100. Malmberg K. Prospective randomised study of intensive insu-lin treatment on long term survival after acute myocardialinfarction in patients with diabetes mellitus. DIGAMI (DiabetesMellitus, Insulin Glucose Infusion in Acute Myocardial Infarc-tion) Study Group. BMJ. 1997;314:1512-5. (Pubitemid 27216066)