UNIVERSITE SAINT-ESPRIT DE KASLIK FACULTE DE MEDECINE
L'ANGINE DE POITRINE
EST UN PRECONDITIONNEMENT ISCHEMIQUE AVANT LA CHIRURGIE DE
REV ASCULARISATION CORONARIENNE CHEZ LES PATIENTS DE GENRE MASCULIN.
These en vue d'obtention d'un doctorat en medecine preparee par
GHIYE Rayanne
So usIa direction duD. MANSOUR Ziad ( chirurgien cardio-vasculaire)
KASLIK-LIBAN 2013-2014
Soutenue le 16 Ma~ 2014 devant le jury compose de
Dr. Boutros Alam Membre
Dr. Georges Choueiry Membre
Dr. Antoine Kosseify
Dr. Nicolas Msallem
Dr. Georges Teddy
President Rapporteur
Membre invite du jury
Resume
Objectifs: Demontrer que l'angine de poitrine agit comme un preconditionnement chez la population masculine dans la chirurgie coronaire.
Methodes : T ous les patients qui ont subi une revascularisation coronaire chirurgicale sous circulation extra-corporelle de janvier 2003 a janvier 2013 au CHU de Strasbourg ont ete consideres. Ont ete exc1u les patients ayant un infarctus du myocarde confinne et les patients de genre feminin. Les patients sont divises en 2 groupes selon l'angine : symptomatiques et asymptomatiques.
Resultats: Nous avons etudie 2221 patients de genre masculin ayant eu une revascularisation coronarienne chirurgicale. Parmi eux, 1660 ont ete
symptomatiques et 561 asymptomatiques. Les groupes ont ete homogenes concernant l'age, le diabete et 1a fraction d'ejection du ventricu1e gauche. Les patients symptomatiques avaient plus d'intoxications tabagique, de dyslipidemie, d'hypertension, et plus d'anastomoses distales.
En postoperatoire, la troponine a ete moindre chez les patients symptomatiques que ce soit ala 6eme heure (4.2±10.6 vs 6.20±17.3; p=0.004) ou ala 24eme heure (8.8±24.9 vs 12.02±33.6 ; p=0.033).
La mortalite intra-hospitaliere chez les patients symptomatiques a ete moindre (1.8% vs 3.4%; p=0.024), ainsi que !'incidence de l'insuffisance renale (6.1% vs 9.4%; p=0.006)
Conclusion: L'angine de poitrine, par le biais du preconditionnement, protege le creur et l'organisme de la morbi-mortalite de la chirurgie coronarienne sous circulation extra-corporelle chez les patients de genre masculin.
Abstract:
Objectives: Prove that angina pectoris has a preconditioning effect in male patients undergoing a coronary surgery.
Methods: All patients undergoing on-pump coronary artery revascularization surgery between January 2003 and January 2013 in Strasbourg university hospital has been considered.
All patients who presented with a confirmed necrosis, and all female patients were excluded. Patients were divided into two groups according to angina pectoris:
symptomatic and asymptomatic.
Results: We studied 2221 male patients having had a surgical coronary revascularization, among which 1660 were symptomatic and 561 were
asymptomatic. Both groups were homogeneous in terms of age, diabetes, and left ventricular ejection fraction. Symptomatic patients were more tobacco smokers, dyslipidemic, hypertensive, and had more distal anastomoses.
Postoperatively, troponin levels were less in symptomatic patients at postoperative hours 6 (4.2±10.6 vs 6.20±17.3; p=0.004) and 24 (8.8±24.9 vs 12.02±33.6;
p=0.033).
Intra-hospital mortality (1.8% vs 3.4%; p=0.024) and incidence of renal failure (6.1% vs 9.4%; p=0.006) were less in symptomatic patients.
Conclusion: Angina pectoris preconditions the heart and the organism from the adverse effects of on-pump coronary surgery in male patients.
Plan de Ia These
I. Avant-Propos ... ... 4 II. Rappel. ... 8
A. L'ischemie B. La reperfusion
C. Le preconditionnement ischemique local D. Le preconditionnement ischemique
a
distanceIII. Ischemies myocardiques d'origine coronariennes ... .14
1. Physiopathologie
2. Circulation coronaire atheromateuse
IV. Angor d'origine non atheromateuse: Angor spastique ... 22 V. Materiels et methodes ... 23
A. Collecte des donnees B. Techniques operatoires C. Statistiques
VI. Resultats ... ... 2 7 A. Caracteristiques demographiques
B. Etude d'homogeneite
C. Resultats biologiques postoperatoires D. Resultats cliniques postoperatoires
VII. Discussion ... ... ... ... 31 VIII. Conclusion ... ... 34 IX. References ... 35
IX.Bibliographie:
( 1) Rapport sur la situation mondiale des maladies non transmissibles 20 10. 20 11.
Geneve, OMS
(2) Global atlas on cardiovascular disease prevention and control. Geneva: WHO;
2011.
(3) Mathers CD, Loncar D . Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(1l):e442.
(4) Lim SS, Vos T, Flaxman AD et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859):2224-2260.
(5) The global burden of disease: 2004 update. Geneva, World Health Organization, 2008.
(6) Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124-36.
(7) Gyurkovics E, Aranyi P, Stangl R, et al. Postconditioning of the lower limb- Protection against the reperfusion syndrome. J Surg Res 2011;169:139-47.
(8) Eberlin KR, McCormack MC, Nguyen JT et al. Sequential limb ischemia demonstrates remote postconditioning protection of murine skeletal muscle. Plast Reconstr Surg 2009;123:8S-16S.
(9) Ren C,Yan Z, Wei D, et al. Limb remote ischemic postconditioning protects against focal ischemia in rats. Brain Res 2009;1288:88-94.
(10) Vinten-Johansen J, Zhao ZQ, Zatta AJ et al. Postconditioning A new link in
nature's armor against myocardial ischemia-reperfusion injury. Basi Res Cardiol 2005;100:295-310.
(11) Van Vuuren D, Lochner A. Ischaemic postconditioning: From bench to bedside. Cardiovasc J Africa 2008;19:311-20.
(12) Charles AL, Guilbert AS, Bouitbir J et a1 . Effect of post-conditioning on mitochondrial dysfunction in experimental aortic cross- clamping. Brit J Surg 2011.
(13) Formigli L, Lombardo LD, Adembri C et al. Neutrophils as mediators to human skeletal muscle ischemia-reperfusion syndrome. Hum Pathol 1992;23:627- 34.
(14) Thompson MM, Nasim A, Sayers RD et al. Oxygen free radical and cytokine generation during endovascular and conventional aneurysm repair. Eur J Vase Endovasc Surg 1996;12:70-5.
(15) Yassin MM, Harkin DW, Barros D'Sa AA et al. Lower limb ischemia- reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction. World J Surg 2002;26:115-21.
(16) Gadaleta D, Fantini GA, Dilane MF et al. Leukotriene generation and pulmonary dysfunction following aortic cross clamp in humans. Ann N Y Acad Sci 1994;723 :4 70-2.
(17) Adembri C, Kastamoniti E, Bertolozzi I, et al. Pulmonary injury follows systemic inflammatory reaction in infrarenal aortic surgery. Crit Care Med 2004;32: 1170-7.
(18) Fantini GA , Conte MS. Pulmonary failure following torso ischemia: clinical
evidence for a remote effect ofreperfusion injury. Am Surg 1995;61:316-9.
(19) Klausner JM, Armer H, Paterson IS, et al. Lower torso ischemia-induced lung injury is leukocyte dependent. Ann Surg 1998;208:761-7.
(20) Tallgren M, Niemi T, PoDyhiaO Ret al. Acute renal injury and dysfunction following elective abdominal aortic surgery. Eur J Vase Endovasc Surg 2007;33:550-5.
(21) Miller CC, Villa MA, Achouh Petal. Intraoperative skeletal muscle ischemia contributes to risk of renal dysfunction following thoracoabdominal aortic repair.
Eur J Cardiothor Surg 2008;33:691-4.
(22) Miller CC, Villa MA, Sutton J et al. Serum myoglobin and renal morbidity and mortality following thoracic and thoraco-abdominal aortic repair: does rhabdomyolysis play a role Eur J Vase Endovasc Surg 2009;37:388-94.
(23) Norwood MG, Bown MJ, Sayers RD. Ischaemia-reperfusion injury and regional inflammatory responses in abdominal aortic aneurism repair. Eur J Vase Endovasc Surg 2004;28:234-45.
(24) Holt SO, Moore KP. Pathogenesis and treatment of renal dysfunction m rhabdomyolysis. Intensive Care Med 2001;27:803-11.
(25) Kuznetsov AV, Veksler V, Gellerich FN et al. Analysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells. Nat Protoc 2008;3:965-76.
(26) Pang CY, Yang RZ, Zhong A et al. Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig. Cardiovasc Res 1995;29:782-8.
(27) Webster RS, Montero EF, Fagundes DJ et al. The role of ischemic
preconditioning at the gracilis muscle of rats in the early phase of reperfusion injury. Acta Chirurgica Brasiliera 2006;21:80-6.
(28) Qi W, Kan SL. Protective effect of ischemic preconditioning duration against ischemia- reperfusion injury of skeletal muscle in rats. Zhongguo Xiu 2005;19:274-7.
(29) Harralson T, Grossi FV, Quan EE et al. Ischemic preconditioning of skeletal muscle. Duration of late-phase protection. Ann Plast Surg 2005;55:216-22.
(30) Pasupathy S, Homer-Vanniasinkam S. Ischaemic preconditioning protects against ischaemia/reperfusion injury: emerging concepts. Eur J Vase Endovasc Surg 2005;29:106-15.
(31) Mattei A , Sutter PM, Marx A et al. Preconditioning with short cycles improves ischemic tolerance on rat fast and slow-twitch skeletal muscle. Eur Surg Res 2000;32:297-304.
(32) Lee HT, Schroeder CA, Shah PM, et al. Preconditioning with ischemia or adenosine protects skeletal muscle from ischemic tissue reperfusion injury. J Surg Res 1996;63:29- 34.
(33) Seifert FC, Banker M, Lane B et al. An evaluation of resting arterial ischemia models in the rat hind limb. J Cardiovasc Res 1985;26:502-8.
(34) GuDrke L, Marx A, Sutter PM et al. Ischemic preconditioning - a new concept in orthopedic and reconstructive surgery. J Surg Res 1996;61: 1-3.
(35) GuDrke L, Marx A, Sutter PM et al. Ischemic preconditioning improves post- ischemic skeletal muscle function. Am Surg 1996;62:391-4.
(36) Saito T, Komiyama T, Aramato H et al. Ischemic preconditioning improves
oxygenation of exercising muscle in vivo. 2004;120: 111-8.
(37) Eastlack RKI Groppo ER, Hargens AR et al. Ischemic-preconditioning does not prevent neuromuscular dysfunction after ischemia-reperfusion injury. J Orthoped Res 2004;22:918-23.
(38) Zahir KD , Syed SA, Zink J, et al. Ischemic preconditioning improves the survival of skin and myocutaneous flaps in a rat model. Plast Reconstr Surg
1998; 102:140-50.
(39) Carroll CM I Carroll SM, Overgoor ML et al. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival. Plast Reconstr Surg 1997;100:58-65.
(40) Schoen M , Rotter R, Gierer P et al. Ischemic preconditioning prevents skeletal muscle tissue injury, but not nerve lesion upon tourniquet-induced ischemia. J Trauma 2007;63:788-97.
(41) Ambros JT I Herrero-Fresneda I, Borau OG et al. Ischemic preconditioning in solid organ transplantation: form experimental to clinics. Transpl Intl2007;20:219- 29.
(42) Martou G, O'Blenes CA, Huang Net al. Development of an in vitro model for study of the efficacy of ischemic preconditioning in human skeletal muscle against ischemia- reperfusion injury. J Appl Physiol2006;101:1335-42.
( 43) Przyklenk K, Bauer B, Ovize M et al. Regional ischemia 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.
Circulation 1993;87:893-9.
( 44) Kharbanda RK , Mortensen UM, White P A et al. Transient limb ischemia
induces remote ischemic preconditioning in vivo. Circulation 2002;106:2881-3.
(45) Kharbanda RK, Li J, Konstantinov IE, et al. Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study. Heart 2006;92:1506-11.
(46) Moses MA, Addison PD, Neligan PC et al. Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction.
Am J Physiol Heart Circ Physiol2005;288:H559-67.
(47) Moses MA, Addison PD, Neligan PC et al. Inducing late phase of infarct protection in skeletal muscle by remote preconditioning: efficacy and mechanism.
Am J Physiol Regul Integr Comp Physiol2005;289:R1609-17.
(48) Harkin DW, Barros D'Sa AA, McCallion K, et al. Ischemic preconditioning before lower limb ischemia-reperfusion protects against acute lung injury. J Vase Surg 2002;35: 1264-73.
( 49) Addison PD, Neligan PC, Ashrafpour H et al. Noninvasive remote ischemic preconditioning for global protection of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol2003;285:H1435-43.
(50) Schmidt M R, Smerup M, Konstantinov IE, et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KA TP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol2007;292:H1883-90.
(51) B0tker HE, Kharbanda R, Schmidt MR et al. 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.
The Lancet 2010;375:727- 34.
(52) D'Ascenzo, F. Presutti DG, PicardiE, et al. Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis. Heart 2012;98:1267-71.
(53) Alreja G, MDI, Bugano D, MD2, Lotfi A, MDI et al. Effect of remote ischemic preconditioning on myocardial and renal injury: meta-analysis of randomized controlled trials. J Invasive Cardiol. 20 12;24:42-8.
(54) Marczaka J, Nowickia R, Kulbackab J et al. Is remote ischaemic preconditioning of benefit to patients undergoing cardiac surgery? Interactive CardioVascular and Thoracic Surgery 2012;14:634-9.
(55) Venugopal V , Hausenloy DJ, Ludman A, et al. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia: a randomised controlled trial .Heart 2009; 95:1567- 71.
(56) Janine M Pilcher. A systematic rev1ew and meta-analysis of the cardioprotective effects of remote ischaemic pre-conditioning in open cardiac surgery. J R Soc Med 2012;105:436-45.
(57) Matthias T, Kottenberg E, Kleinbongard P, et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised,double-blind, controlled trial. Lancet 2013;382:597-604.
(56) Hausenloy DJ, Candilio L, Laing C et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 2007;370:575-79.
(57) Candilio L, Malik A, Ariti C et al. The effects of multi-limb remote ischaemic preconditioning in patients undergoing cardiac bypass surgery. Heart 20 13;99: 123.
(58) 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.
(59) Veighey K , Macallister RJ. Clinical applications of remote ischemic preconditioning. Cardiol Res Pract 2012: Article ID 620681.
(60) Walsh SR, Umar Sadat, Jonathan R. Boyle et al. Remote ischemic
preconditioning for renal protection during elective open infrarenal abdominal aortic aneurysm repair: randomized controlled trial. Vase Endovascular Surg 2010;44:334--40.
(61) Schwartz L, Kloner RA, Arai AE et al. New horizons in cardioprotection:
recommendations from the 2010 National Heart,Lung, and Blood Institute Workshop. Circulation 20 11; 124: 1172-9.
(62) Hausenloy DJ, Candilio L, Laing Cet al. Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double- blinded controlled clinical trial. Clin Res Cardiol2012;101:339-48.
(63) Garcia S, Rector TS, Zakharova MY, The Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES, NCT: 01558596) J Clin Trials Clinical Trials Cellular Immunology ISSN: 2167-0870 JCTR
(64) Patel MR, Dehmer GJ,Hirshfeld JW, et al.
ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT 2012 appropriate use criteria for coronary revascularization focused update.
(65) Pitcher JM, Wang M, Tsai BM et al. Preconditioning: gender effects. J Surg
Res 2005;129:202-20.
(66) Rossouw JE, Anderson GL, Prentice RL, et al. Hormones, genetic factors, and gender differences in cardiovascular disease. Cardiovasc Res 2002;53:5.
(67) Baker L, Meldrum KK, Wang Metal. The role of estrogen in cardiovascular disease. J Surg Res 2003;115:325.
(68) Hodis HN, Mack WJ, Lobo RA, et al. Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001; 135:939.
( 69) Mendelsohn ME , Karas R. H. The protective effects of estrogen on the cardiovascular system. N Engl J Med 1999;340: 1801.
(70) Colditz GA, Willett WC, Stampfer MJ, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987; 316: 11 0 5.
(71) Schwarzenberger JC, Sun LS, Pesce MA et al. Sex-based differences in serum cardiac troponin I, a specific marker for myocardial injury, after cardiac surgery. Crit Care Med 2003;31 :689.
(72) Tunstall-Pedoe H, Morrison C, Woodward M, et al. Sex differences in myocardial infarction and coronary deaths in the Scottish MONICA population of Glasgow 1985 to 1991. Presentation, diagnosis, treatment, and 28-day case fatality of3991 events in men and 1551 events in women. Circulation 1996;93:1981.
(74) Cardiologie, Elsevier masson. Chapitre 1 : Atherome, epidemiologie et physiopathologie, le malade polyatheromateux,
(75) Cardiologie, Elsevier masson. Chapitre 4: Angine de poitrine et infarctus myocardique.
(76) Cardiologie, Elsevier masson. Chapitre 5 : Douleur thoracique aigue et chronique.
