Evaluation of reactive hyperemia and ischemia-reperfusion using the EndoPAT

Normal functions of endothelial cells include mediation of coagulation,
platelet adhesion, immune function, and control of volume and electrolyte
content of the intravascular and extravascular spaces. In case of endothelial
dysfunction, the normal biochemical processes carried out by the endothelium
are disturbed. Endothelial dysfunction can result from disease processes, as
occurring in hypercholesterolemia, septic shock, hypertension, and diabetes, as
well as from environmental factors, such as smoking. Endothelial dysfunction is
thought to be a key event in the development of atherosclerosis, and has also
been shown to be of prognostic significance in predicting vascular events
including stroke and heart attacks1. Endothelial function has been shown to be
impaired in patients with coronary artery disease (symptomatic and
asymptomatic), type II diabetes mellitus, hypertension, obesity, and
hypercholesterolemia 2-9. Importantly, several prominent researchers state that
endothelial dysfunction might be the causal pathological mechanism behind
metabolic diseases (*common soil hypothesis*).
Endothelial function can be measured using non-invasive and invasive
techniques. CHDR has recently acquired a device that allows non-invasive
measurement of vaso-reactivity: the EndoPAT (Peripheral Arterial Tone). The
main applications of this device are the measurement of the arterial pulse wave
at a finger artery during rest and after occlusion of the blood flow in the arm
(reactive hyperemia) and to estimate arterial stiffness (augmentation index).
However, it is reasonable to assume that the device can also be used to study
ischemia-reperfusion (I/R) phenomena by increasing the duration of the
occlusion. Therefore a study is proposed to investigate whether read-outs of
the device after prolonged arterial occlusions may be suitable parameters to be
used as biomarkers for I/R-injury. As at present the experience with the device
is limited, the development of the I/R model will be preceded by a series of
experiments to document the performance of the device, as described in this
protocol. This includes experiments on intra- and inter-individual variability,
diurnal variability, and age and gender differences. Also the influence of
known modulators of endothelial function (smoking, food and xanthine intake,
etc.) will potentially be addressed.
As it is likely that the experiments will be influenced by the tone of the
autonomic nervous system, recording of heart rate variability will be done
simultaneously. Previously, CHDR used another non-invasive device (Finapres) to
record the arterial pulse wave. This device will also be used in the proposed
experiments.

The objectives are to explore in a step-wise approach the possibility to study
reactive hyperemia and ischemia-reperfusion phenomena in humans by simultaneous
assessment of vaso-reactivity and autonomous nervous system function.

The study will be carried out as an open, observational study.

na