clinical assessment of endothelium dysfunction

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Clinical assessment of endothelium dysfunction

Clinical assessment of endothelium dysfunction

Principle There are both invasive and non-invasive techniques for exploring various aspects of the pathobiology of the endothelium of arteries and veinsThe basic principle, however, is similar: Healthy arteries dilate in response to pharmacological and/or physiological stimulation of the endothelium due to release of NO and other vasoactive substances. In disease states, such endothelium-dependent dilatation is reduced or absent

Invasive assessmentA. Coronary Epicardial and Microvascular FunctionChanges in the epicardial and microvascular responses to endothelium dependent pharmacological agents are measured during cardiac catheterization using quantitative coronary angiography and the Doppler flow-wire techniques.

Preserved epicardial coronary endothelial function is characterized by vasodilatation in response to acetylcholine which promotes the release of NO Arteriosclerotic vessels with impaired endothelial function, however, respond with vasoconstriction as a result of a direct vasoconstrictor effect of ACh on the vascular smooth muscle (muscarinic effect) in the absence of NO release

Response of healthy endothelium

Similar induced functional changes in vascular reactivity have been demonstrated with other endothelium dependent and endothelium independent pharmacological substancesPhysical measures of endothelium-dependent responses include exercise which induce an increase in coronary blood flow and thus shear stress on the coronary circulation, which leads to flow-mediated endothelium-dependent vasomotion of the epicardial vesselsSimilar responses can be seen in response to mental stress

Another physiological test to assess epicardial vasoreactivity is the use of the cold pressor test in which the subject puts his or her hand into ice waterThe activation of the sympathetic nervous system leads to release of NO and endothelium-derived hyperpolarizing factors via stimulation of endothelial 2-adrenergic receptors and consequently vasodilation in healthy arteriesHowever, in dysfunctional endothelium, 1-adrenergicmediated constriction of smooth muscle cells will dominate, closely mirroring the responses to acetylcholine

Coronary flow reserve is the ratio of maximal coronary blood flow during maximal coronary hyperemia with provocative stimuli (such as adenosine infusion, pacing, or exercise) divided by the resting coronary blood flowThis maximal blood flow response (coronary flow reserve) is both endothelium- and non endothelium-dependent, and a coronary flow reserve 6 h)No smoking or any tobacco consumption at least 6 h before studyNo exercise or food/beverages that contain alcohol or caffeine or are rich in polyphenols (cocoa, tea, fruit juices) for >12 hNo vitamins for at least 72 hVasoactive medications withheld on the morning of the study if possible with careful noting of the use and timing of any drugsNo exercise >12 h before testQuiet, temperature-controlled roomIn female patients, repetitive studies should be made at the same time of the menstrual cycle (ideally on days 17 of the menstrual cycle)Rest for at least 10 min before measurementsSupine positionArm resting comfortable with cradle support with the imaged artery at the heart levelTest should be performed at the same time of the day (especially if multiple tests are performed)

2. Sphygmomanometer probe position and cuff occlusion timePlacement of the cuff 12 cm distal to the elbow creaseOther sites are discouraged because proximal cuff positioning affects the magnitude of the peak vasodilatory responseOcclusion time, 5 min (shorter inflation attenuates FMD response)Cuff inflation to at least 50 mm Hg above systolic pressure

3. Site selectionBrachial artery with a minimum diameter (usually 2 mm); small arteries are difficult to measure, and changes in absolute diameter correspond to big relative changesIf repetitive measurements are planned, site has to been replicated; anatomic landmarks should be used

4. Image acquisitionLongitudinal images obtained by high-resolution ultrasound (7.512 MHz)A clear interface between the near and far arterial wall should be achievedDiameter measurements are obtained in end diastole or averaged over the heart cycleStereotactic adjustable prop holding is essential to ensure image qualityRecording of the baseline diameter for at least 1 minSimultaneous acquisition of pulse-wave Doppler velocity signals for quantification of shear stress (stimulus) if feasible; insonation angle should be


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