Review articles
Current Concepts in Assessment of Microvascular Endothelial Function Using Laser Doppler Imaging and Iontophoresis

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Effective evaluation of endothelial function is a powerful tool for determining patients at risk of development and progression of cardiovascular disease. As an alternative to invasive tests of endothelial function, several noninvasive methods have been developed, including the use of laser Doppler flowmetry/imaging to measure cutaneous perfusion accompanied by iontophoresis of acetylcholine and sodium nitroprusside. It is clear from previous studies that this technique provides an easy, validated, and reproducible method for investigators to assess and monitor endothelial function in patients with a variety of pathologic conditions, but it may also be used to examine disease progression over time and responsiveness to treatment, thereby facilitating clinical trials. However, a standardization of protocols would help reduce the apparent controversy seen in the literature. With its increasing use by other groups, it is anticipated that further published studies will help to provide a better understanding of the development and progression of cardiovascular disease.

Section snippets

Endothelial Function, Laser Doppler, and Iontophoresis: A Brief Overview

Endothelial dysfunction is a pivotal phenomenon in cardiovascular disease (CVD) that precedes structural changes in blood vessels and clinical manifestations. Accordingly, much recent research has focused on the early detection of endothelial dysfunction in humans. Endothelial dysfunction is typically characterized by reduction of the bioavailability of several active vasodilators (eg, nitric oxide [NO]) with a concurrent increase in bioavailability of endothelium-derived contracting factors

Iontophoresis of Vasoactive Drugs

Iontophoresis is defined as the introduction, by means of a direct electrical current, of ions of soluble salts into the tissues of the body. The basic principle of iontophoresis is that molecules of drugs in solution that are positively or negatively charged will migrate across the skin under the influence of an applied current according to the rule that like charges repel each other (Banga and Chien 1988). The apparatus used for iontophoresis shown (Figure 1) consists of a ring-shaped chamber

Cutaneous Blood Flux Rather Than Blood Flow

A limitation of LDI/LDF is that researchers cannot be sure what volume of tissue is being measured. Thus, rather than perfusion being measured quantitatively, it is expressed as blood flux in arbitrary perfusion units. As flux is a function of volume of blood multiplied by velocity, high laser Doppler readings can be generated either by a large volume of slowly moving blood or a small volume of fast moving blood, which may confound results. Fortunately, this can be differentiated by looking at

Experimental Setup

Iontophoresis allows the delivery of vasoactive drugs to the skin without the trauma associated with intradermal injection/microdialysis; the quantity of drug delivered is also too negligible to have any systemic side-effects and avoids first-pass metabolism. However, mild local allergic reactions and skin irritations have been reported in some individuals (Ramsay et al. 2002). It is vital that all possible factors that affect vasoactivity remain constant throughout the study, for example, the

Recent Clinical Studies Using Iontophoresis and Laser Doppler

In recent years, iontophoresis drug delivery accompanied by laser Doppler technology has been increasingly used to measure endothelial function in a variety of pathologic conditions. Hansell et al. (2004) studied the relationship between vascular responses to endothelial-dependent vasodilatation in small cutaneous vessels and the brachial artery, using LDF and flow-mediated dilatation, respectively. They found a significant correlation between the two measurements in apparently healthy subjects

Summary

Recent advances in the laser Doppler technique show that it offers a valuable method for endothelial function testing. As detailed above, among its advantages are the ability to look at endothelial function in one type of tissue (skin microcirculation) and its safety for use in children. Despite some limitations, we believe that in association with a method of measuring arterial endothelial function (eg, flow-mediated dilatation) laser Doppler with associated iontophoresis provides an effective

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      Of note, the cutaneous microcirculation is an accessible and representative vascular bed that can be used for the evaluation of systemic microcirculatory flow and reactivity (Holowatz et al., 2008). Laser Doppler perfusion monitoring (LDPM) is a noninvasive method for the evaluation of systemic microvascular endothelial function, and LDPM has already proven useful in many clinical conditions (Turner et al., 2008), including cardiovascular and metabolic diseases (de Moraes et al., 2016; Gomes et al., 2008; Kaiser et al., 2013), rheumatologic diseases (Ruaro et al., 2017; Weibel et al., 2007) and circulatory shock (either septic or cardiogenic) (Mongkolpun et al., 2020; Orbegozo et al., 2018). Most published data concerning LDPM have validated the site of the skin of the forearm for the measurements, which is more accessible and more representative of general skin microvascular function (Cracowski and Roustit, 2016).

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