Innovative technique for assessment of endothelial dysfunction
In 1998, F. Murad, R.Furshgotu and L. Ignarro were awarded the Nobel Prize in medicine for a series of studies on the role of endothelium in the pathogenesis of cardiovascular disease. Since 1998, the endothelial dysfunction (ED) has become an urgent interdisciplinary problem. ED always preceds a damage to or a dysfunction of any blood vessel, regardless of its organ localization. This applies to arteries, veins, and all structural components of microcirculation. ED is recognized as a universal mechanism, which is involved in all the risk factors for major vascular events, and underlies the pathogenesis of a wide range of socially significant diseases.
Several potential markers of endothelial dysfunction have been identified: tissue plasminogen activator and its inhibitor, thrombomodulin, and Von Willebrand factor. Other markers are also known but are still used mainly in research, due to their high cost and the poor reproducibility of their effects. Tests for these biomarkers are available only in specialized laboratories, moreover, these tests are quite labor intensive and cannot be widely used in medical practice.
In contrast, indirect non-invasive methods are also available for evaluation of endothelial function: acetylcholine- or serotonin-dependent vasodilatation of the brachial artery and a reactive hyperemia. These methods for evaluation of vasoconstrictive or vasodilating endothelial function identify the effects of endothelium-dependent stimulus on the diameter of the vessel and/or the blood flow through it. Pharmacological stimuli, such as acetylcholine, or mechanical stimuli, a brief occlusion of the vessel, may be used in a functional test. The effects of the external stimuli are observed by a real-time angiographic or ultrasound imaging. Blood flow may be measured dopplerographically, for example, by intravascular sensors. Disadvantages of the ultrasound method include the lack of standardization and the significant dependence of test results on the skills and training level of the operator.
Evaluation of the properties of endothelium involves study of blood flow in small vessels, which is typically accomplished by optical methods such as photoplethysmography and laser Doppler flowmetry (LDF). Spectral analysis of the variable component of the LDF signal allows an assessment of vascular tone and the action of different blood flow regulation mechanisms in the microvasculature.
Wavelet analysis of low-amplitude oscillations of skin temperature is an innovative approach to assessment of endothelial dysfunction. The test takes 20 minutes in accordance with the local thermal functional test procedure. The vasodilation indices (VI), the relative oscillation amplitude changes during and after the test, are used as the quantitative results of the test.
The vasodilation index (VI) values are in the range of 1.5 ... 4.5 for healthy control group and are below than 1 in the case of ED. A comparative example of VI values for a healthy group and for type 2 diabetes patients groups of varying condition severity is shown in the Figure below.