Le « Remote Conditioning » Pourquoi s’en priver? Pr Fabrice Prunier EA 3860 « Cardioprotection, Remodelage et Thrombose » & Service de Cardiologie, CHU d � Angers, France Réseau INSERM RIRE : Réseau Infarctus de REperfusion
Infarct size is a determinant of mortality Gibbons et al. JACC 2004;44:1533-1542
L’infarctus de reperfusion
Remote Preconditioning • Anesthetized dogs • Remote intraorgan preconditioning • 4 episodes of 5min LCX occlusion interspersed with 5min reperfusion before 1h LAD occlusion • 35% reduction of infarct size (similar range than direct LAD preconditioning) Przyklenk et al. Circulation 1993;87:893-99
Remote Perconditioning rats Kerendi et al. Basic Res Cardiol 2005;100:404-12
Remote conditioning Hausenloy and Yellon. Cardiovasc Res 2008
Remote Ischemic Conditioning in Human G. Heusch Lancet 2013;381:166-75
Patient Recruitment and Randomization 4x 5/5 200 mmHg ECG Randomization Ambulance Patient Bøtker et al. ACC 2009
Primary Endpoint: Myocardial Salvage Index Acute scan: Area-at-risk (AAR) Salvage index = (AAR-FIS)/AAR One month scan: Final infarct size (FIS) Bøtker et al. ACC meeting 2009
Primary Endpoint: Myocardial Salvage Index p=0.02 Salvage Index (median [IQR]) 1 0.76 0.56 .5 0 PCI only rIPerC Bøtker et al. ACC meeting 2009
RIPOST-MI (Remote Ischemic POSTconditioning in Myocardial Infarction) SCA ST+ <6h Dotation SFC/FFC 2011 (80 000 € ) Randomisation Traitement RIPer + IPost RIPer conventionnel RIPer = 3 X 5/5min RIPer = 3 X 5/5min IPost = 4 X 1/1 min Objectif principal: Taille de la nécrose sur cinétique CPK-MB Biocollection Réseau INSERM RIRE Prunier et al. Unpublished data
RIPOST-MI study Dotation SFC/FFC 2011 Brest& PHRC 2011 Angers& Tours& Lyon& Toulouse& Montpellier& Réseau INSERM RIRE Prunier et al. Unpublished data
Prunier et al. Unpublished data
Alors pourquoi s’en priver? • Facile à faire • Sans effet secondaire • Sous surcoût • Intérêt potentiel pour infarctus, AVC, chirurgie cardiaque, transplantation… Mais… • Absence de donnée sur des critères durs dans de larges études de morbi-mortalité • Mécanisme incomplètement compris
CONCLUSION New perspective in reperfusion: cardioprotection with a conditioning approach Remote conditioning
Back-up slides
Remote conditioning Kharbanda et al. Lancet 2009
Apolipoprotéine A-I : un médiateur du conditionnement à distance Hibert et al. PlosOne 2013
151#randomized#pa.ents#with#STEMI# 44#assigned#to#Control#group# 36#assigned#to#RIper#group# 71#assigned#to#Riper+IPost#group# 24#excluded#because#did#not# 16#excluded#because#did#not# 51#excluded#because#did#not# meet#study#criteria# meet#study#criteria# meet#study#criteria# ####12#TIMI2/3#flow#before#PTCA# ####10#TIMI2/3#flow#before#PTCA# ####22#TIMI2/3#flow#before#PTCA# #####7#inappropriate#loca.on#of# #####6#inappropriate#loca.on#of# ####12#inappropriate#loca.on#of# ########coronary#artery#occlusion# ########coronary#artery#occlusion# ########coronary#artery#occlusion# #####2#CKMB#missing#points#(death)# ###### #####1#CKMB#missing#points#(death)# #####1#external#electric#shock# # #####3#external#electric#shock# ########within#first#3#days# # ########within#first#3#days# #####1#TIMI#0/1#aRer#PTCA# # ####13#inappropriate#case#for# #####1#urgent#cardiac#surgery## # #########direct#sten.ng#procedure# (septal#defect)# # # 3#excluded#at#the#.me#of#blinded# 2#excluded#excluded#at#the#.me# 0#excluded#at#the#.me#of#blinded# analysis# of#blinded#analysis# analysis# ####1#significant#collateral# #####1#significant#collateral# # ########circula.on#(Rentrop#2)# ########circula.on#(Rentrop#2)# # #####1#uninterruptable#AUC#CKMB# #####1#TIMI#1#aRer#PTCA# # #######because#of#missing#points# # # ####1#previous#MI#in#the#same# # # ########coronary#territory# # # 17#eligible#for#CKMB#analysis# 18#eligible#for#CKMB#analysis# 20#eligible#for#CKMB#analysis# Unpublished data
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