Acute and subacute effect of rheopheresis on microvascular endothelial function in patients suffering from age-related macular degeneration.

This study was performed on seven patients affected by the atrophic form of age-related macular degeneration (AF-ARMD). The patients under investigation belonged to a larger study aimed at evaluating the efficacy of rheopheresis treatment (RT) on the visual function of AF-ARMD patients. Following the protocol of the larger study, patients received RT twice a week, every two weeks, for a total of ten treatments, as well as high-dose supplementation with zinc and vitamins A, E and beta-carotene. Recruited patients underwent skin laser Doppler flowmetry coupled with skin iontophoresis of the endothelium-dependent vasodilator acetylcholine (ACh) and a test of skin post-ischemic reactive hyperemia, before and after the first RT (time 1: all seven patients) and the fifth RT (time 2: six patients). A significantly higher absolute (anova for repeated measures) and relative (percentage change from the baseline) skin blood flux response (SBFR) to ACh iontophoresis was observed after RT, compared to before RT at time 1 (679 +/- 43% and 436 +/- 78%, respectively; P < 0.05), as well as before RT at time 2 compared to before RT at time 1 (683 +/- 74% and 436 +/- 78%, respectively; P < 0.05). Absolute and relative SBFR to ischemia did not differ either after RT compared to before RT at time 1, or before RT at time 2 compared to before RT at time 1. These findings are consistent with an acute and subacute beneficial effect of RT on skin microvascular endothelial function in the studied AF-ARMD patients.

Skin vasodilator effect of exogenous urotensin-II in hypertensives not exposed to antihypertensive medication.

To investigate the effect of urotensin-II (U-II) on skin vascular tone in normotensive subjects and in patients with essential arterial hypertension (EHT), forearm skin blood flux and skin blood flowmotion (SBF) response to U-II cathodal iontophoresis was investigated using laser Doppler flowmetry (LDF) and spectral Fourier analysis in 10 young normotensive subjects, before and after intra-dermal injection of the nitric oxide synthetase inhibitor N(G)-monometil-l-arginine (L-NMMA). Forearm skin blood flux response to U-II cathodal iontophoresis was also investigated using LDF in 15 newly diagnosed EHT patients, in 15 long-standing EHT patients and in 15 age- and sex-matched normotensive subjects. Intra-dermal injection of L-NMMA significantly blunted the increase in skin blood flux (from 342.5+/-153.0% to 193.5+/-78.9%, p<0.05) and completely inhibited the increase in spectral amplitude of 0.009-1.6 Hz total-spectrum SBF, as well as of the 0.009-0.02 Hz component, related to endothelial activity, which occurred following U-II iontophoresis in normotensive subjects. A significant increase in skin blood flux compared with baseline was also induced by U-II iontophoresis in newly diagnosed (354+/-195% change from baseline) and long-standing patient (324+/-180% change from baseline), without significant difference with normotensive subjects (400+/-251% change from baseline). These findings demonstrate that: (i) U-II exerts a skin vasodilator effect in normotensive subjects, which is partly endothelial-dependent; (ii) U-II skin vasodilator effect is preserved in newly diagnosed and in long-standing EHT patients.

Blunted post-ischemic increase of the endothelial skin blood flowmotion component as early sign of endothelial dysfunction in chronic kidney disease patients.

With the aim to investigate microvascular endothelial function in chronic kidney disease (CKD) patients on conservative treatment, skin blood flowmotion (SBF) was explored by spectral Fourier analysis of skin forearm laser Doppler tracing, registered before and following forearm ischemia in 32 III to V stage CKD patients (23 males, mean age: 52+/-12 years), without diabetes or cardiovascular disease, and in 32 age and sex matched healthy subjects. The power spectral density (PSD) of the 0.009-1.6 Hz total spectrum SBF, as well as of five sub-intervals, each of them related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6 Hz) or cardiac (0.6-1.6 Hz) activity, was measured in PU(2)/Hz (PU=perfusion unit; 1 PU=10 mV). Under basal conditions CKD patients and controls did not differ in skin perfusion or in PSD of total spectrum SBF, as well as of each of the five subintervals considered. No substantial difference was also observed in skin post-ischemic hyperemia between patients and controls. A significant post-ischemic increase in the normalized value of endothelial sub-interval was observed in controls (p<0.05, GLM ANOVA analysis of variance), but not in CKD patients. A lower per cent increase in absolute PSD value of endothelial sub-interval was also observed in CKD patients compared to controls (185+/-98 % vs 279+/-243 %, p<0.05). The post-ischemic per cent increase in absolute PSD of endothelial sub-interval was negatively related to the systolic blood pressure (r=-0.45, p<0.01), to the mean arterial blood pressure (r=-0.40, p<0.05) and to the PTH serum levels (r=-0.38, p<0.05) in CKD patients. The blunted post-ischemic increase of the endothelial SBF sub-interval can be considered an early sign of microvascular endothelial dysfunction in the CKD studied patients. Arterial hypertension seems to be the main factor related to this SBF abnormality, together with the hormonal CKD related abnormalities.

Spectral analysis of laser Doppler skin blood flow oscillations in human essential arterial hypertension.

The aim of this study was to investigate whether human essential arterial hypertension (EHT) is associated with modification of the skin blood flowmotion (SBF), which could be a sign of skin microcirculatory impairment. Forearm skin perfusion was measured by laser Doppler flowmetry (LDF) in conventional perfusion units (PU) before and after ischemia in 20 middle-age newly diagnosed EHT untreated patients, in 20 middle-age long standing EHT treated patients and in 30 age and sex matched healthy normotensive subjects (NS). Power spectral density (PSD) of SBF total spectrum (0.009-1.6 Hz), as well of five different frequency intervals (FI), each of them related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6) or cardiac (0.6-1.6) activity, was also measured in PU(2)/Hz before and after ishemia, using Fourier analysis of LDF signal. The three studied groups did not differ in basal and post-ischemic skin perfusion or in basal SBF parameters considered. However, while a significant post-ischemic increase in PSD of total spectrum SBF (P < 0.001) and of its different FI, with the only exception of respiratory FI, was observed in NS, a significsnt post-ischemic increase in PSD was observed only for total spectrum (P < 0.01) and for endothelial FI (P < 0.001) in newly diagnosed EHT patients and only for myogenic FI (P < 0.05) in long standing EHT patients. These findings suggest that the mechanisms which mediate the post-ischemic increment of SBF are perturbed earlier in human EHT than the mechanisms which mediate the skin post-ischemic hyperaemia. The same findings also suggest that the impairment of the endothelial mechanism involved in SBF control occurs by the time in the course of EHT.