Endothelial Dysfunction

The endothelium is the thin layer of cells lining the interior of every vessel in the circulatory system. It plays a central role in processes such as blood pressure regulation and tissue perfusion. Endothelial cells can produce nitric oxide (NO), which causes relaxation of the smooth muscle cells lining the vessels and thereby vasodilation. Endothelial dysfunction is characterized by a disturbed endothelium-dependent vasodilation and decreased bioavailability of NO. It has been observed in several diseases and has been widely studied as it is often an early disease event in these.

Source: Stijn A.I. Ghesquiere, University of Maastricht

An increasing amount of evidence links microvascular dysfunction to cardiovascular outcomes: it can be a predictor for stroke and heart attacks. The endothelial function can be studied by performing tests that cause endothelium-dependent and/or independent vasodilation. These tests include post occlusive reactive hyperemia (PORH), local heating (thermal challenge) and iontophoresis.

Post Occlusive Reactive Hyperemia (PORH)

Vascular function can be assessed by observing the response to reactive hyperemia. Reactive hyperemia is an increase in blood flow as a result of a temporary occlusion of an arterial blood supply leading to an oxygen deficit. Patients with impaired endothelial function show a different response than healthy controls. The test is done by performing an arterial occlusion, usually by using a blood pressure cuff, typically for several minutes. After the occlusion, the pressure is suddenly released, causing a large influx of blood into the previously occluded tissue. The perfusion is measured before, during and after the occlusion and several parameters related to both magnitude of the perfusion and the time it takes to change can give information about the vascular health of the patient.

Post Occlusive Reactive Hyperemia

The perfusion can be measured using a laser Doppler probe or a laser speckle contrast imager.

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Thermal challenge/Heat provocation

Local heating of the skin may elicit near maximal vasodilatation. In healthy individuals the response to thermal hyperemia demonstrates a predictable pattern. It is characterized by an initial peak in skin blood perfusion, involving the sensory afferents, and a secondary rise and plateau mediated by NO release.

Read more about heat provocations.

Thermal Challenge

The perfusion can be measured using a laser Doppler probe or a laser speckle contrast imager.

The heat can be controlled using a PeriFlux System 5000 with a heat control unit and a laser doppler probe with heat or a transparent water-filled heat probe for the imager.


Iontophoresis

Iontophoresis is a technique to transport charged molecules or drugs across a tissue barrier. Combined with the laser Doppler or laser speckle techniques, iontophoresis is a valuable tool for diagnosis and studying endothelial dysfunction.

Iontophoresis

The perfusion can be measured by laser Doppler using a specialized delivery electrode with integrated laser Doppler probe or a laser speckle contrast imager, using a transparent delivery electrode for use with the imager.

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Case example:

The Microcirculation in Obesity and type 2 Diabetes

Dr. Alfons J.H.M. Houben Dept. of Internal Medicine, Maastricht University Medical Center+ and School for Cardiovascular Diseases (CARIM), Maastricht, The Netherlands

The focus of my research for many years has been microvascular dysfunction (MVD) as both a cause and a consequence of (cardio)metabolic diseases (see 1 for our working hypothesis). One important function of the microcirculation is to deliver oxygen/nutrients to all tissues and to remove waste products. In normal metabolism this includes the delivery of glucose, which taken up by the gut following a meal, to skeletal muscle in order to be stored as glycogen.

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