End Ot Helium
Transcript of End Ot Helium
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VASCULAR ENDOTHELIUM &
ITSFUNCTIONAL ASSESSMENT
Upa KukongviriyapanDepartment of Physiology, Faculty of Medicine
Khon Kaen University, Thailand.
B.Sc. Experimental Pathology
Queen Marys School of Medicine and Dentistry
The Royal London HospitalOctober 12, 2005
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Topic Contents
Structure and functions of vascularendothelial cell.
The endothelial dysfunction.
The oxidant- stress induced endothelial
dysfunction.
How to assess endothelial functions. Summary
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The Normal Vascular Endothelium
Historically viewed as a passivevascular lining.
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Vascular Endothelium
Many important roles to maintain vascular homeostasis:
Vascular tone regulation
VSMC proliferation
Inflammatory responses
Haemostasis
It produces and releases vasoactive, thromboregulatory
and growth factor substances.
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Tousoulis, et al., Heart 2005; 91: 353-358.
Endothelial cell functions
Maintaining the vascular tone: Vasodilation and Vasoconstriction
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Functional targets Physiological action/Mediators
Growth Stimulation Inhibition
PDGF, FGF NO, PGI2, TGF
IGF-1, ET, AII
Endothelial cell functions
Inflammation Proinflammatory AntiinflammatoryAdhesion molecules
Selectin-E, VCAM-1, ICAM-1, PECAM-1
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Functional targets Physiological action/Mediators
Haemostasis Prothrombotic Antithrombotic
PAI-1 PGI2, TPA
Endothelial cell functions
Calles-Escandon and Cipolla, Endocrine Rev 2001; 22: 36-52.
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Factors affecting vascular tone and structure
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- pathological conditions
- altered anticoagulant &
anti-inflammatory properties
- impaired modulation of
vascular growth &
dysregulation of vascular
remodeling
An impairment of endothelium-dependent vasorelaxationcaused by a loss of NO bioactivity in the vessel wall.
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Unifying model: Endothelial dysfunction to CVD
Xanthine oxidase, NADP/NADPH oxidase
uncoulpled eNOS
NO bioavailability
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How can we assess the
endothelial function?
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Methods for exploring endothelial function.(Guerci et al., Diabetes Metab 2001; 27: 425-434.)
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Clinical Studies Supporting the Prognostic Value ofEndothelial Vasomotor Function Testing.(Ganz, et al. Circulation 2003; 108: 2049-2053.)
Patients with endothelial dysfunction had a far greater incidence of adverse
cardiovascular events in follow-up compared with patients with preserved
endothelial function.
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Key points for evaluating ED.
Tousoulis D, et al., Heart 2005; 91: 353-358.
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Evaluating Endothelial Function in Humans
Non-invasive techniques
High resolution ultrasonography: Assessment of
flow-mediated dilatation (FMD). Strain-gauge plethysmography: Evaluation of
forearm blood flow (FBF).
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Flow-mediated dilatation (FMD)Is defined as an endothelium-
dependent process that reflects therelaxation of a conduit artery whenexposed to increased flow and,thereby, increased shear stress.An impaired FMD response reflectsendothelial dysfunction.A temporary increase in shear stresscan be induced by increasing the localblood flow, the so-calledre
active hyperemia.
An abrupt decrease in vascularresistance mediated by the EDNOcaused FMD.
Tousoulis D, et al., Heart 2005: 91: 553-558.
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The genesis of FMD
Moens, et al., Chest 2005; 127: 2254-2263.
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Flow-mediated vasodilation (FMD)
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Equipment: Ultrasonic imaging of
brachial artery diameter
Measurement of vasodilation response by
ultrasonic imaging of arterial diameter: should be equipped
with vascular software
for 2D imaging, colorand spectral Doppler, an
internal ECG monitor
and high frequency
vascular transducer
attached to a high-quality
mainframe ultrasound.and
Noninvasive, simple, costly, widely available, need further
validation.
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Brachial Artery Flow-Mediated Dilation
Baseline 5 Minutes Post-Occlusion
Blood Pressure Cuff
Occlusion 1 Minute
Release
3.1 mm 3.6 mm
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Forearm blood flow
(Strain-gauge plethysmography)
Noninvasive, simple, reproducible and less observerdependent, need further validation.
The strain-gauge is attached to the upper forearm, andconnected to plethysmographic device.
.
FBF is measured by temporarily occluding the venousreturn (by a cuff inflated to 40 mmHg) and measuredthe slight swelling of the distal portion of the limb dueto continued arterial inflow.
d f
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The initial rate of swellingrepresents the arterial inflow.
The technique evaluates the
percentage change of flowfrom baseline to themaximum flow duringreactive hyperaemia following
a five minute ischaemia of theforearm.
Forearm blood flow
(Strain-gauge plethysmography)
Tousoulis D, et al., Heart 2005: 91: 553-558.
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Sample window
The FBF is estimated by the gradient of the tangent to the curveduringthe first cardiac cycles.
Result of forearm flow is expressed as ml/100 ml tiss/min or thepercent changes in flow.
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Timetable of FMD & FBF
Tousoulis D, et al., Heart 2005; 91: 353-358.
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Application in clinical trials
Study design:Acute or long-term intervention trials.Sample size:A crossover or a parallel- group design study.
Methodology:Select most reproducible results.
Evaluating precision of the technique.
Individual trainingin the principles and technical
aspect of Doppler ultrasonography and Strain-gaugeplethysmography.
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SUMMARY
Endothelial functional testing can be used as anindicator for vascular damage or vascular disease and also
other diseases relating to oxidative stress conditions.
Reversal of endothelial dysfunction protects against
progression of vascular disease.
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Proposed new tests for evaluating endothelial functionshould be developed with optimal characteristics;
Cost-effective, reproducible and standardization.
Ability to predict risk and relationship to establishedtests of risk.
Useful as a screen for drug development.
Can identify individual patients.
Can predict a reduction in the risk of clinical events.
SUMMARY
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QUESTIONS
What are the main functions of the vascular endothelial
cell?
What is the endothelial dysfunction? How can it lead tothe cardiovascular disease?
How can we evaluate the endothelial functions?
What are the key points for evaluating the
endothelial dysfunction?
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The End For Now
But there is much more to learn!!!!
Thank you!