End Ot Helium

7/30/2019 End Ot Helium

1/31

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


2/31

Topic Contents

Structure and functions of vascularendothelial cell.

The endothelial dysfunction.

The oxidant- stress induced endothelial

dysfunction.

How to assess endothelial functions. Summary


3/31

The Normal Vascular Endothelium

Historically viewed as a passivevascular lining.


4/31

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.


5/31

Tousoulis, et al., Heart 2005; 91: 353-358.

Endothelial cell functions

Maintaining the vascular tone: Vasodilation and Vasoconstriction


6/31

Functional targets Physiological action/Mediators

Growth Stimulation Inhibition

PDGF, FGF NO, PGI2, TGF

IGF-1, ET, AII


Inflammation Proinflammatory AntiinflammatoryAdhesion molecules

Selectin-E, VCAM-1, ICAM-1, PECAM-1


7/31

Functional targets Physiological action/Mediators

Haemostasis Prothrombotic Antithrombotic

PAI-1 PGI2, TPA


Calles-Escandon and Cipolla, Endocrine Rev 2001; 22: 36-52.


8/31

Factors affecting vascular tone and structure


9/31

- 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.


10/31


11/31


12/31

Unifying model: Endothelial dysfunction to CVD

Xanthine oxidase, NADP/NADPH oxidase

uncoulpled eNOS

NO bioavailability


13/31

How can we assess the

endothelial function?


14/31

Methods for exploring endothelial function.(Guerci et al., Diabetes Metab 2001; 27: 425-434.)


15/31

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.


16/31

Key points for evaluating ED.

Tousoulis D, et al., Heart 2005; 91: 353-358.


17/31

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).


18/31

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.


19/31

The genesis of FMD

Moens, et al., Chest 2005; 127: 2254-2263.


20/31

Flow-mediated vasodilation (FMD)


21/31

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.


22/31

Brachial Artery Flow-Mediated Dilation

Baseline 5 Minutes Post-Occlusion

Blood Pressure Cuff

Occlusion 1 Minute

Release

3.1 mm 3.6 mm


23/31

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


24/31

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.


25/31

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.


26/31

Timetable of FMD & FBF

Tousoulis D, et al., Heart 2005; 91: 353-358.


27/31

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.


28/31

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.


29/31

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


30/31

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?


31/31

The End For Now

But there is much more to learn!!!!

Thank you!

Documents

End Ot Helium