Pathophysiology and Clinical Applications of Nitric Oxide (Endothelial Cell Research)

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PAT measurements in patients with chest pain 67 and coronary artery disease 68 seem to correlate well with the assessment of endothelial function performed by both intracoronary infusion of acetylcholine during angiography 20 and FMD brachial artery ultrasound, although the strength of the correlation varies between studies.. This might be due to the daily variability of endothelial responses, but also to other factors that may have affected the peripheral vascular responses to ischemia. Once again, it appears as a compulsory requirement to adhere to a strict protocol when performing these assessments.

Given the noninvasive nature of the procedures, these methods can be used in most people and measurements can be repeated to monitor changes in status. These aspects, in addition to the high reproducibility of measurements, mainly due to the high level of automation of at least some of the methods described above, make the techniques useful for clinical practice.. At present, these techniques are mainly used for research purposes in projects assessing disease mechanisms in humans but they show a remarkable potential as surrogate endpoints and may prove useful in the assessment of pharmacological and nonpharmacological intervention and trials dealing with disease prevention..

Assessment of endothelial function may help in patient risk stratification in primary and secondary prevention, the evaluation of vascular responses to specific therapies, and longitudinal patient monitoring. Noninvasive techniques have become available which might help in the assessment of endothelial dysfunction in clinical practice.

There are however many unresolved issues in relation to the utility of these techniques in everyday clinical practice. From a technical perspective, several issues should be investigated thoroughly before these techniques can be recommended for routine use. Firstly, we need to establish whether they are truly and precisely assessing endothelial function or whether they reflect the combined effect of the many variables??

Secondly, it is important to study whether they will truly show a direct correlation with the effects of intervention.


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As most of these techniques assess endothelial function in an indirect way and are affected by the presence of external agents, protocols should be defined rigorously to minimize the effects of these confounding factors. Efforts should focus on automation to make the results more technician-independent and improve the reproducibility of their measurements.. Conceivably, the use of these techniques in clinical practice could improve patient risk stratification, help in the implementation of preventive strategies, and also improve treatment monitoring.

Although several studies have already been performed Table 2 , further research is required in large clinical studies using the appropriate gold standards for the assessment of the role of this methodology in relation to diagnosis and intervention. So far, there is not enough evidence to support the use of endothelial function assessment in clinical practice. Comparisons among the different tools for risk assessment currently used in clinical practice and the assessment of endothelial function should also be carried out..

Table 2. Other potential clinical applications include the dynamic monitoring of treatment as, in contrast to conventional CV risk factors, endothelial function is a dynamic event. Hence, these novel techniques should allow a better short-term assessment. Evidence to document that this is the case would require 2 steps. First, it should be established?? Second, studies should be performed to demonstrate that intensification of treatment leading to improved endothelial function improves patients??

Future areas of interest also include the relationship of endothelial dysfunction to circulating endothelial progenitor cells number and function and their therapeutic modulation, as well as genetic factors influencing endothelial function. Until answers to these questions become available, these techniques will remain useful research tools..

Part II - Nitric Oxide and Shear Stress

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Pages January Download PDF. Antonio L. Corresponding author. This item has received. Article information. Palabras clave:. We describe the basic principles, the main protocols to perform these techniques, and their clinical value based on the scientific evidence. Endothelial function. Introduction In the fight against cardiovascular CV diseases, preventive strategies are becoming the focus of attention.

This manuscript will focus on the different techniques available for the assessment of endothelial function in clinical practice. Endothelial dysfunction The term endothelial dysfunction is widely used to describe any form of abnormal activity of the endothelium. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy..

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The Vascular Endothelium and Human Diseases

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A Novel Ruthenium-based Molecular Sensor to Detect Endothelial Nitric Oxide

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Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.. N Engl J Med. Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.. Close relation of endothelial function in the human coronary and peripheral circulations..


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