Η ΣΗΜΑΣΙΑ ΤΗΣ ΜΕΛΕΤΗΣ ΤΟΥ ΕΝΔΟΘΗΛΙΑΚΟΥ ΓΛΥΚΟΚΑΛΥΚΑ ΣΤΙΣ ΚΑΡΔΙΑΓΓΕΙΑΚΕΣ ΠΑΘΗΣΕΙΣ

Transcription

1 Η ΣΗΜΑΣΙΑ ΤΗΣ ΜΕΛΕΤΗΣ ΤΟΥ ΕΝΔΟΘΗΛΙΑΚΟΥ ΓΛΥΚΟΚΑΛΥΚΑ ΣΤΙΣ ΚΑΡΔΙΑΓΓΕΙΑΚΕΣ ΠΑΘΗΣΕΙΣ ΙΓΝΑΤΙΟΣ(ΟΙΚΟΝΟΜΙΔΗΣ ΕΠΙΚΟΥΡΟΣ(ΚΑΘΗΓΗΤΗΣ(ΚΑΡΔΙΟΛΟΓΙΑΣ Β (ΠΑΝΕΠΙΣΤΗΜΙΑΚΗ(ΚΑΡΔΙΟΛΟΓΙΚΗ(ΚΛΙΝΙΚΗ(ΕΚΠΑ ΝΟΣΟΚΟΜΕΙΟ(ΑΤΤΙΚΟΝ

2 Endothelial+Glycocalyx +. S Reitsma, DW Slaaf, H Vink et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007

3 Endothelial+Glycocalyx of+at+least+200+nm+on+the luminal+side+of+healthy vasculature plays+a+vital+role+in vascular+permeability

4 Endothelial+glycocalyx:+a+vital+role+in+vascular permeability+and+inflammation

5 Endothelial+Glycocalyx Damage+to+the+endothelial glycocalyx+is+associated+with influx+of+lipoproteins, leakage+of+macromolecules adhesion+of+circulating+cells+to the+endothelium. to+an+imbalance+in+enzymatic systems+such+as+coagulation+and antioxidant+defence+as+well+as+an impaired+no+release. Lekakis J, Ikonomidis I,Vlachopoulos C Eur J Cardiovasc Prev Rehabil Dec;18(6):775-89

6 METHODS(TO(ASSESS(GLYCOCALYX Electron(microscopy((Luft(JH(1966) Intravital(miscroscopy TwoGphoton(laser(scanning(microscopy (antibodies(against(glycocalyx(proteins(with(fluoresence(properties) (

7 METHODS(TO(ASSESS(GLYCOCALYX in(vivo Noninvasive:(a(semiautomated(imaging(method to(estimate(glycocalyx(thickness(by OPS((Orthogonal(Polarization(Spectral(imaging) SDF((Sideview(Darkfield(imaging) at(the(superficial(microvasculature this(imaging(method(uses(the(erythrocyte endothelium(gap(of(the(capillaries(in(the(image to(quantify(glycocalyx(thickness.

8 Increased)PBR:)an)accurate)index)of reduced)endothelial)glycocalyx)thickness

9 GLYCOCHECK)CAMERA 1.)Collected)movie)frame)(Ν=40) 2.)Vascular)segments)defined)(Ν=75) Small vascular segments every 10 μm along the length of the detected vasculature: 840 radial intensity profiles are obtained for RBC-perfused lumen

10 GLYCOCHECK)CAMERA R B C c ol u m n w id t h ( μ m )!! 3.)For)each)vascular)segment:)calculation)of RBC)column)width)for)series)of)consecutive frames Frames 40!frames!x!75!segments=3000 DURATION!:3min! 4.)For)each)vascular)segment:)calculation)of)PBR! Dperf!(RBC;perfused!lumen) P50 (RBCW) PBR)(Perfused)Boundary)Region) PBR=(Dperf) )RBCW))/)2 Glycocalyx!(RBC permeable) Outer!edge!of RBC;perfused core

11 MICROSCAN)CAMERA!

12 GLYCOCALYX(EXAMINATION!!

13 GLYCOCALYX(RESULTS (Microns) (Microns)

14 NORMAL'VALUES'REPRODUCIBILITY

15 Endothelial+glycocalyx+damage Hypercholesterolemia+(partial+reversal+by statins Acute+Hyperglycemia Association+with+carotid+IMT+in+type+1+diabetes Renal+disease InflammationAsepsis + + Lekakis J, Ikonomidis I,Vlachopoulos C Eur J Cardiovasc Prev Rehabil Dec;18(6):775-89

16 Endothelial+glycocalyx+thickness+in+various cohorts + Results of Perfused Boundary Region (PBR) in healthy controls (n=20), hypertensives (n=101), smokers (n=130), patients with psoriasis (n=72) and diabetics (n=36).*p<0.05 patients vs controls. Laboratory of Preventive Cardiology, Attikon Hospital AHA 2013

17 EFFECT%OF%SMOKING%REDUCTION%ON ENDOTHELIAL%GLYCOCALYX%AND ARTERIAL%WAVE%REFLECTION%DURING MEDICALLY7AIDED%SMOKING CESSATION%PROGRAM I.IKONOMIDIS,%K.%KOUREA,%G.%PAVLIDIS,%I.%TSOUGOS, M.%MARINOU,%I.%PAPADAKIS,%H.%TRIANTAFYLLIDI, M.%ANASTASIOU7NANA,%J.%LEKAKIS UNIVERSITY*OF*ATHENS*MEDICAL*SCHOOL,*ATTIKON*HOSPITAL, 2ND*DEPARTMENT*OF*CARDIOLOGY,*ATHENS,*GREECE AHA*2013*Circulation.*2013;128:A12610

18 RESULTS SMOKERS (N=180) p* NON3SMOKERS (n=40) p# BASELINE 12;WEEKS Cigarettes,;n 31±8 6±9 < <0.05 CO,;ppm 32±18 10±13 < ±1.1 <0.05 PBR,;microns 2.03±0.17! PWVc,;m/sec 10±2! AI,;% 33±18! *!Baseline!vs.!12!weeks!in!smokers #!Smokers!vs.!non5smokers!at!baseline 1.93±0.24 < ±0.14 < ±2! NS 8.5±2 < ±10 < ±10 <0.05

19 GLYCOCALYX(RESULTS!

20 baseline (Microns) 3/months/post/cessation GLYCOCALYX RESULTS (Microns)

21 RESULTS Baseline 3"months"post cessation

22 RESULTS'(3(months(post(smoking cessation PBR$was$related$with$CO (r=0.88,$p<0.05) PBR$was$related$with$AI (r=0.47,$p<0.05)

23 CONCLUSION Endothelial+glycocalyx+thickness+is+reduced+in smokers+compared+to+non+smokers. Medically8aided+ smoking+ reduction contributes+ to+ restoration+ of+ endothelial glycocalyx+ thickness+ and+ reduction+ of abnormal+wave+reflections. Improvement+ of+ endothelial+ glycocalyx+ is linked+ with+ improved+ arterial+ elasticity+ during smoking+cessation. + +

24 I.Ikonomidis, A. Voumvourakis, M. Varoudi, I. Papadakis, G. Pavlidis, H. Triantafyllidi, M. Anastasiou-Nana, J. Lekakis Second Department of Cardiology, University of Athens Medical School, Attikon University Hospital, Athens, Greece. ΑΗΑ#2013,##Circulation.#2013;128:A11263

25 RESULTS Compared to controls, hypertensives HYPERTENSIVES (Ν=101) CONTROLS (Ν=50) PBR 2,02±0,17 1,89±0,14 PWVc 10±2 8,5±2 csbp 140±21 95±20 cpp 46±17 30±5 AI 28±16 15±10 CFR 2,5±0,7 3,5±1 GLS -17±4-22±2,5

26 Glycocalyx and central SBP R=0.50 p<0.01

27 Glycocalyx and PWV R=0.47 p<0.01

28 Glycocalyx thickness and CFR in hypertensives R=0.40 p<0.05

29 Relationship arterial stiffness, coronary flow reserve with myocardial strain qincreased PWV and csbp were related with: Ø reduced GLS (r=0,35, r=0,40) Ø reduced CFR (r=-0,40, r=-0,35) (p<0,05 for all associations) qreduced CFR was also associated with impaired GLS (r=0,36) (p<0,05)

30 Conclusion Endothelial glucocalyx -is impaired in newly diagnosed untreated hypertensives and -is related with abnormal aortic elastic properties and coronary microcirculatory function leading to impaired LV longitudinal deformation

31 Intact&glycocalyx&in&associated&with&fetuin:&a&biofactor preventing&vascular&calcification&in&psoriasis!! r=$0.48,!p<0.05

32 Glycocalyx(thickness(increases(post(antinflammatory treatment(in(parallel(with(fetuin(increase(and(reduction (of(oxidative(stress P<0.05 P<0.05 P<0.05

33 ΣΥΜΠΕΡΑΣΜΑ Η)μελέτη)του)ενδοθηλιακού)γλυκοκαλυκα είναι)εφικτή)με)νέες)μη)επεμβατικές)τεχνικές Αποτελεί)μια)νέα)ερευνητική)πρόκληση)για την)πρώιμη)διάγνωση)αγγειακής)βλάβης)και την)παρακολούθηση)θεραπευτικών παρεμβάσεων

34 ! ΕΥΧΑΡΙΣΤΩ*ΓΙΑ*ΤΗΝ*ΠΡΟΣΟΧΗ*ΣΑΣ

35 Glycocalyx(thickness(increases(post(antinflammatory treatment(in(parallel(with(fetuin(increase(and(reduction (of(oxidative(stress P<0.05 P<0.05

36 Damage&of&the&Endothelial&Glycocalyx&in&Dialysis Patients

37 METHODS The$ perfused$ boundary$ region$ (PBR)$ in microvessels$ is$ the$ cell<poor$ layer$ which results$ from$ the$ phase$ separation$ between the$flowing$red$blood$cells$(rbc)$and$plasma. The$ PBR$ includes$ the$ most$ luminal$ part$ of glycocalyx$that$does$allow$cell$penetration. Increased$PBR$is$considered$an$accurate$index of$ reduced$ endothelial$ glycocalyx$ thickness because$of$a$deeper$penetration$of$the$rbc$in the$glycocalyx. $

38 Endothelial+Glycocalyx+in+Sepsis De Backer D et al: Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med 2002, 166: JL Vincent and D De Backer: Microvascular dysfunction as a cause of organ dysfunction in severe sepsis. Critical Care 2005, 9(suppl 4):S9-S12

39 METHODS We#examined#119*smokers#(55%#males,#age:#48± 8y)#without#cardiovascular#disease#treated#with transdermal#nicotine#patches#(60%) and/or#varenicline#(40%) ##at#before,#4#and#12#weeks#after#treatment#during validated#smoking#cessation#program. Twenty* non5smokers# of#similar#age#and#sex served#as#controls.

40 METHODS We#measured: a) Exhaled. carbon. monoxide. (CO,. ppm)# and self.reported#number.of.cigarretes/day b) CarotidBfemoral. pulse. wave. velocity#(pwvc m/sec#.#complior#sp#alam)#and#augmentation index#(ai%#.#arteriograph,#tensiomed) c) Perfused. boundary. region# (PBR)# of# the sublingual# arterial# microvessels# (ranged# from 5.25# micrometers)# using# Sideview# Darkfield imaging#(microscan,#glycocheck) #

41 Oscillometric+technique+(Arteriograph)!

42 STUDY&POPULATION SMOKERS NON1SMOKERS p n Age,&y 48±8 42±5 NS Male&sex,&n&(%) 65&(55) 10&(50) NS BMI,&Kg/m2 27.3± ±3.3 NS Hypertension, n&(%) Dyslipidemia, n&(%) 26&(22) 0&(0) < &(42) 0&(0) <0.05 Diabetes,&n&(%) 7&(6) 0&(0) NS Family&history,&n (%) 34&(28) 2&(10) NS

43 METHODS In 101 untreated patients (age: 54±11 years) with essential hypertension and 20 controls of similar age and sex we measured : carotid-femoral pulse wave velocity (PWVc m/sec-complior ) central systolic blood pressure (csbp-mmhg) pulse pressure (cpp-mmhg) augmentation index (Augmentation index, AI% -Arteriograph) LV longitudinal (GLS -%) strain, using speckle tracking coronary flow reserve (CFR) of the LAD after adenosine infusion using Doppler echocardiography Perfused boundary region (PBR)

44 RESULTS'(3(months(post(smoking cessation CO#was#related#with#PWVc#(r=0.53, p<0.05) CO#was#related#with#AI (r=0.47,#p<0.05)