Skin Laser Doppler Flowmetry Research Articles

Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial

Despite convincing animal data, there is an ongoing debate on whether and how fructose affects blood pressure in humans. The aim of this study was to investigate the effects of fructose restriction on blood pressure, and the role of endothelial function herein. forty-four overweight individuals were asked to follow a fructose-restricted diet (<7.5g/meal and <10g/day) for 6 weeks. They were randomly assigned to double-blind supplementation with glucose (=intervention group) or fructose (=control group) powder three times daily. Office blood pressure was measured with an automated device, and endothelial function was assessed by reactive hyperemia peripheral arterial tonometry, skin laser doppler flowmetry, and serum sE-selectin. Thirty-seven participants completed the study. Systolic blood pressure decreased significantly in the intervention group (change from baseline:-3.3mmHg; 95%CI:-8.8,- 0.3), but this change was not statistically different from the control group. In contrast, diastolic blood pressure decreased significantly in the intervention group in comparison to controls (difference:-4.0mmHg; 95%CI:-9.5,-0.5). Furthermore, the change in fructose intake was associated with the change in diastolic blood pressure (beta: 0.085mmHg; 95% CI: 0.032;0.138). The endothelial markers were not affected by the intervention. Finally, the effects of the intervention on diastolic blood pressure appeared to be higher in individuals consuming high amounts of salt at baseline (difference:-9.0mmHg; 95%CI:-14.5,-2.5). Six-week fructose restriction per se results in a dose-dependent decrease in diastolic blood pressure. Further studies are warranted to elucidate the effects of fructose restriction on salt-sensitive hypertension in humans. www. gov; NCT03067428.

Effects of regular physical exercise on skin blood flow and cardiovascular risk factors in overweight and obese subjects

Objective: it is well known that low omentin levels and reduced bioavailability of nitric oxide (NO) are outgrowth of obesity. Besides, in obese subjects, microvascular dysfunction can be an initial stage of cardiovascular diseases. This situation can be evaluated with skin laser–Doppler flowmetry (LDF).Methods: in this study we investigated the effects of 12 weeks moderate physical exercise on microvascular reactivity and plasma levels of omentin and NO in 25 overweight and obese subjects. Control group was composed of 28 sedentary participants who were neither obese nor overweight. Microvascular reactivity was handled by measurement of skin blood flow from the ring finger of the right hand with LDF, which is a non–invasive method for evaluation. With this method, it was aimed to examine the post–occlusive reactive hyperemia response of the patients. None of the participants in both groups have never followed a regular exercise schedule in their life span.Results: with regular exercise, there was a statistically significant decrease in glucose (p=0.008), cholesterol (p=0.05), and triglyceride (p=0.048) levels, while body mass index, high–density lipoprotein, and low–density lipoprotein levels did not change significantly in overweight/obese group. Also, the omentin level significantly increased (p=0.01), but NO level did not change significantly. Moreover, the amount of change in omentin and NO levels measured before and after the physical exercise were significantly correlated (r=0.57). Considering the microcirculation, rest flow (p=0.001) and peak flow value of LDF (p=0.001) increased after the physical exercise.Conclusion: our study shows that moderate physical exercise affects microvascular reactivity and plasma levels of omentin in overweight and obese subjects.

Synchronized research on endothelial dysfunction and microcirculation structure in dorsal skin of rats with type 2 diabetes mellitus.

The aim of this study was to explore changes in the microvascular tone as measured by laser Doppler flowmetry (LDF) and the microcirculation structure of the dorsal skin of rats with type 2 diabetes mellitus. The diabetic rat model was induced by a diet of high-sugar and high-lipid fodder combined with the injection of streptozotocin into the abdominal cavity. Depending on the interval between the development of diabetes and the experiments, the diabetic rats were subdivided into three groups. The evaluation of microvascular tone was based on the amplitude responses of the LDF signal fluctuations in the appropriate frequency range in the dorsal skin of the rats during a thermal test (at 42°C). The nitric oxide (NO) level in plasma was also used as a marker of endothelial dysfunction. Changes in the microcirculation structure in the diabetic rats were estimated by measuring the microvascular density in the choke vessels of the dorsal skin of the rats. The experimental results with respect to red blood cell (RBC)-related parameters showed decreased hematocrit and hemoglobin levels and increased standard deviation of the width of the RBC distribution in three diabetic rats. The increasing fluctuation amplitudes diminished in the endothelial frequency range in response to the thermal test and this was accompanied by abnormal NO levels in plasma of the diabetic groups as compared with healthy rats. A significant reduction in the microvascular density of the choke vessels of the dorsal skin was found only in the diabetic group at the most advanced stage of diabetes in this experiment. Thus, we suggest that endothelial dysfunction occurs in diabetic rats and changes in the microcirculation structure of the dorsal skin occur in a later stage of diabetes development. A. Photograph of measurement method by using a LDF probe and heating device in the dorsal skin of the rat. B. Dorsal skin LDF signals of a healthy rat during the thermal stimuli test. (a) Blood flow signal record for the test. Wavelet filtration of blood flow signal in (b) myogenic range, (c) neurogenic range, and (d) endothelial range.

Kidney and vascular function in adult patients with hereditary fructose intolerance

Objective: Previous studies have shown that patients with hereditary fructose intolerance (HFI) are characterized by a greater intrahepatic triglyceride content, despite a fructose-restricted diet. The present study aimed to examine the long-term consequences of HFI on other aldolase-B-expressing organs, i.e. the kidney and vascular endothelium.Methods: Fifteen adult HFI patients were compared to healthy control individuals matched for age, sex and body mass index. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV) and endothelial function by peripheral arterial tonometry, skin laser doppler flowmetry and the endothelial function biomarkers soluble E-selectin [sE-selectin] and von Willebrand factor. Serum creatinine and cystatin C were measured to estimate the glomerular filtration rate (eGFR). Urinary glucose and amino acid excretion and the ratio of tubular maximum reabsorption of phosphate to GFR (TmP/GFR) were determined as measures of proximal tubular function. Results: Median systolic blood pressure was significantly higher in HFI patients (127 versus 122 mmHg, p = .045). Pulse pressure and cf-PWV did not differ between the groups (p = .37 and p = .49, respectively). Of all endothelial function markers, only sE-selectin was significantly higher in HFI patients (p = .004). eGFR was significantly higher in HFI patients than healthy controls (119 versus 104 ml/min/1.73m2, p = .001, respectively). All measurements of proximal tubular function did not differ significantly between the groups.Conclusions: Adult HFI patients treated with a fructose-restricted diet are characterized by a higher sE-selectin level and slightly higher systolic blood pressure, which in time could contribute to a greater cardiovascular risk. The exact cause and, hence, clinical consequences of the higher eGFR in HFI patients, deserves further study.

Novel Noninvasive Assessment of Microvascular Structure and Function in Humans.

Optical coherence tomography (OCT) is a novel high-resolution imaging technique capable of visualizing in vivo structures at a resolution of ~10 μm. We have developed specialized OCT-based approaches that quantify diameter, speed, and flow rate in human cutaneous microvessels. In this study, we hypothesized that OCT-based microvascular assessments would possess comparable levels of reliability when compared with those derived using conventional laser Doppler flowmetry (LDF). Speckle decorrelation images (OCT) and red blood cell flux (LDF) measures were collected from adjacent forearm skin locations on 2 d (48 h apart), at baseline, and after a 30-min rapid local heating protocol (30°C-44°C) in eight healthy young individuals. OCT postprocessing quantified cutaneous microvascular diameter, speed, flow rate, and density (vessel recruitment) within a region of interest, and data were compared between days. Forearm skin LDF (13 ± 4 to 182 ± 31 AU, P < 0.05) and OCT-derived diameter (41.8 ± 6.6 vs 64.5 ± 6.9 μm), speed (68.4 ± 9.5 vs 89.0 ± 7.3 μm·s), flow rate (145.0 ± 60.6 vs 485 ± 132 pL·s), and density (9.9% ± 4.9% vs 45.4% ± 5.9%) increased in response to local heating. The average OCT-derived microvascular flow response (pL·s) to heating (234% increase) was lower (P < 0.05) than the LDF-derived change (AU) (1360% increase). Pearson correlation was significant for between-day local heating responses in terms of OCT flow (r = 0.93, P < 0.01), but not LDF (P = 0.49). Bland-Altman analysis revealed that between-day baseline OCT-derived flow rates were less variable than LDF-derived flux. Our findings indicate that OCT, which directly visualizes human microvessels, not only allows microvascular quantification of diameter, speed, flow rate, and vessel recruitment but also provides outputs that are highly reproducible. OCT is a promising novel approach that enables a comprehensive assessment of cutaneous microvascular structure and function in humans.

Age, waist circumference, and blood pressure are associated with skin microvascular flow motion: the Maastricht Study.

Skin microvascular flow motion (SMF)--blood flow fluctuation attributed to the rhythmic contraction and dilation of arterioles--is thought to be an important component of the microcirculation, by ensuring optimal delivery of nutrients and oxygen to tissue and regulating local hydraulic resistance. There is some evidence that SMF is altered in obesity, type 2 diabetes mellitus, and hypertension. Nevertheless, most studies of SMF have been conducted in highly selected patient groups, and evidence how SMF relates to other cardiovascular risk factors is scarce. Therefore, the aim of the present study was to examine in a population-based setting which cardiovascular risk factors are associated with SMF. We measured SMF in 506 participants of the Maastricht Study without prior cardiovascular event. SMF was investigated using Fourier transform analysis of skin laser Doppler flowmetry at rest within five frequency intervals in the 0.01-1.6-Hz spectral range. The associations with SMF of the cardiovascular risk factors age, sex, waist circumference, total-to-high-density lipoprotein cholesterol, fasting plasma glucose, 24-h SBP, and cigarette smoking were analysed by use of multiple linear regression analysis. Per 1 SD higher age, waist circumference and 24-h SBP, SMF was 0.16 SD higher [95% confidence interval (CI) 0.07, 0.25; P < 0.001), -0.14 SD lower (95% CI -0.25, -0.04; P = 0.01), and 0.16 SD higher (95% CI 0.07, 0.26; P < 0.001), respectively, in fully adjusted analyses. We found no significant associations of sex, fasting plasma glucose levels, total-to-high-density lipoprotein cholesterol ratio, or pack years of smoking with SMF. Age and 24-h SBP are directly, and waist circumference is inversely associated with SMF in the general population. The exact mechanisms underlying these findings remain elusive. We hypothesize that flow motion may be an important component of the microcirculation by ensuring optimal delivery of nutrients and oxygen to tissue and regulating local hydraulic resistance not only under physiological conditions but also under pathophysiological conditions when microcirculatory perfusion is reduced, such as occurs with ageing and higher blood pressure. In addition, obesity may result in an impaired flow motion with negative effects on the delivery of nutrients and oxygen to tissue and local hydraulic resistance.

Body mass index is related to microvascular vasomotion, this is partly explained by adiponectin.

obesity-related microvascular dysfunction, including alterations in rhythmic changes in vascular diameter, so-called 'vasomotion', may be important in the clustering of obesity with other cardiovascular risk factors. Adipokines have been suggested to play a role in obesity-related vascular dysfunction. Alterations in vasomotion have been found using extreme body mass index (BMI) phenotypes. Whether these alterations can be translated to the general population is unknown. The aim was to retrospectively investigate relationships between BMI, vasomotion and adipokines in a population-based cohort. Adiposity, vasomotion, adiponectin and leptin were determined in 94 apparently healthy participants (age 42 years, 46 men, mean BMI 25·5 ± 3·8 kg/m(2) ) of the Amsterdam Growth and Health Longitudinal Study (AGHLS). Vasomotion was assessed via wavelet analysis of skin laser Doppler flowmetry (LDF). BMI was associated with the neurogenic domain of the vasomotion spectrum (β -0·011, P = 0·046), adiponectin (β -0·18, P = 0·028) and leptin (β 2·22, P < 0·0001). Adiponectin was positively associated with the neurogenic domain of vasomotion (β 0·016, P = 0·019). Leptin did not show any significant relationship with vasomotion. The association between BMI and the neurogenic domain of the vasomotion spectrum was partly explained by adiponectin. The association between adiposity and microvascular vasomotion also applies to the normal population and is partly explained by adiponectin.

Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease.

Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory patterns of LDF have probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed.

Correlation of skeletal muscle blood oxygenation level‐dependent MRI and skin laser doppler flowmetry in patients with systemic sclerosis

To investigate the origin of skeletal muscle BOLD MRI alterations in patients with systemic sclerosis (SSc) by correlating BOLD MRI T2* signal of calf muscles with microcirculatory blood flow of calf skin measured by laser Doppler flowmetry (LDF). BOLD MRI (3T) and LDF measurements were performed in 12 consecutive SSc patients (6 women, 6 men; mean age 54.0 ± 10.0 years) and 12 healthy volunteers (4 men, 8 women; mean age 44.7 ± 13.1 years). For both modalities, the same cuff compression paradigm at mid-thigh level was used. LDF datasets were acquired using a PeriScan PIM II Imager (Perimed AB, Stockholm, Sweden) at the upper calf corresponding to the level of MR imaging. Cross-correlations of BOLD and LDF signal intensity changes depending on time lags between both time series were calculated. Maximal cross-correlations of BOLD T2* and LDF measurements were calculated as 0.93 (healthy volunteers) and 0.94 (SSc patients) for a BOLD time lag of approximately 10 s. Key parameter analysis suggested that in contrast to hyperemic BOLD signal loss at maximum value in SSc patients, ischemic T2* decrease cannot be explained by differences of tissue perfusion. Skeletal muscle BOLD T2* signal in SSc patients is closely correlated with changes of microperfusion as detected by LDF.

Toxic and drug-induced peripheral neuropathies

This review discusses publications highlighting current research on toxic, chemotherapy-induced peripheral neuropathies (CIPNs), and drug-induced peripheral neuropathies (DIPNs). The emphasis in clinical studies is on the early detection and grading of peripheral neuropathies, whereas recent studies in animal models have given insights into molecular mechanisms, with the discovery of novel neuronal, axonal, and Schwann cell targets. Some substances trigger inflammatory changes in the peripheral nerves. Pharmacogenetic techniques are underway to identify genes that may help to predict individuals at higher risk of developing DIPNs. Several papers have been published on chemoprotectants; however, to date, this approach has not been shown effective in clinical trials. Both length and nonlength-dependent neuropathies are encountered, including small-fiber involvement. The introduction of new diagnostic techniques, such as excitability studies, skin laser Doppler flowmetry, and pharmacogenetics, holds promise for early detection and to elucidate underlying mechanisms. New approaches to improve functions and quality of life in CIPN patients are discussed. Apart from developing less neurotoxic anticancer therapies, there is still hope to identify chemoprotective agents (erythropoietin and substances involved in the endocannabinoid system are promising) able to prevent or correct painful CIPNs.

Functional Changes in Microcirculation in Miners in Relation to the Length of Underground Work

Objective: to study microcirculation in miners in relation to the length of their underground work. Subjects and methods. Microcirculation was studied in 328 miners who were divided into three groups according to the length of their underground work. It was examined in the skin of the outer lower third of the shoulder, by applying skin laser Doppler flowme-try by means of a ЛАКК-01 laser capillary blood flow analyzer (Lazma RPA, Russian Federation). Results. The performed studies determined a relationship between microcirculatory changes and the length of underground work. Group 1 (length, 1—9 years) showed a decrease in the major indicator of microcirculation through various mechanisms aimed at reducing peripheral resistance. As the length of underground work was more, there was an increase in total peripheral resistance and blood flow bypass. Conclusion. Microcirculatory deterioration occurs in miners who have worked underground longer. The found changes are comparable with the stages of total adjustment syndrome. The stress stage developing in miners with an underground work length of 1 to 9 years is characterized by decreased peripheral resistance. The resistance stage of adjustment syndrome occurs when different compensatory mechanisms are activated in miners who have been working under harmful conditions for 10 to 19 years. Dysadjustment signs characterized by increases in peripheral resistance and blood flow bypass occur with exhaustion of compensatory systems in miners who have been working underground for 20 years or more. Key words: microcirculation, miners, length of underground work.

Investigation of skin vasoreactivity and blood flow oscillations in hypertensive patients

In order to evaluate whether arterial hypertension (AH) affects skin microcirculation, 46 newly diagnosed, never-treated, hypertensive patients and 20 healthy normotensive controls underwent a forearm skin postocclusive reactive hyperaemia (PORH) test, using laser-Doppler flowmetry (LDF). Their resting skin blood flow oscillations (SBFOs) were also investigated using wavelet spectral analyses of skin LDF tracings within six frequency subintervals in the 0.005-2 Hz spectral range. To evaluate whether antihypertensive treatment affects skin microcirculation, the same measurements were repeated in 22 of the recruited hypertensive patients after 8 ± 2 weeks of antihypertensive treatment. Significantly reduced PORH, together with significantly higher spectral amplitudes within the majority of the investigated SBFO subintervals, was found in untreated hypertensive patients compared with controls. In the 22 hypertensive patients who completed the follow-up, there was a significant increase in PORH after antihypertensive treatment compared with before (357 ± 178 vs. 284 ± 214%, respectively, P < 0.05). Following antihypertensive treatment, the same 22 hypertensive patients did not differ significantly from controls either in PORH or in the majority of the investigated SBFO frequency subintervals. This study showed reduced skin vasoreactivity in the hypertensive patients, confirming that antihypertensive treatment negatively affects skin microcirculation. The short period of efficacious antihypertensive treatment resulted in normalization of skin vasoreactivity in hypertensive patients who completed the follow-up, suggesting that antihypertensive treatment affects positively skin microcirculation in AH. The SBFO increase in untreated hypertensive patients, and its almost complete normalization in treated hypertensive patients, suggests that SBFO enhancement in untreated hypertensive patients could be an adaptive reversible response to AH.

Skin Vasodilator Function and Vasomotion in Patients with Morbid Obesity: Effects of Gastric Bypass Surgery

Obesity-associated microvascular dysfunction (MVD) involves different body tissues, including skin, and concurs to increased cardiovascular risk in obese patients (Ob-P). Generalized improvement of MVD is an important goal in obesity treatment. Since skin MVD mirrors generalized systemic MVD, skin microvascular investigation in prospective studies in Ob-P may surrogate microvascular investigation in organs more important for cardiovascular risk of the studied patients. In this prospective study, we measured forearm skin post-occlusive reactive hyperaemia (PORH), as percentage flow increase from baseline, and skin vasomotion in 37 Ob-P before Roux-en-Y gastric bypass (RYGB), and in 24 of them about 1 year after RYGB, using laser Doppler flowmetry (LDF). The spectral contribution of skin LDF signal oscillations in the frequency intervals of 0.01-0.02 Hz, 0.02-0.06 Hz, and 0.06-0.2 Hz--corresponding to endothelial-, sympathetic-, and myogenic-dependent vasomotion, respectively, was measured by means of spectral Fourier analysis. The same measurements were also performed in 28 healthy, lean subjects (HLS). Before RYGB, Ob-P had a significant reduction in PORH and in the all vasomotion parameters investigated, compared with HLS. After RYGB, Ob-P who completed the follow-up, had a significant weight loss (∼40 kg on average), together with a full normalisation in PORH and in vasomotion parameters, regardless of diabetes status. Surgically induced sustained weight loss resulted in full normalisation of skin microvascolar function in Ob-P about 1 year after RYGB. This result suggests a beneficial effect of sustained weight loss on generalized MVD of the studied Ob-P.

Local heat stress and skin blood flowmotion in subjects with familial predisposition or newly diagnosed hypertension

Objective. The aim of the study was to investigate the skin microcirculation blood flow and flowmotion response to heat stress in normotensive subjects with familial predisposition to hypertension and in hypertensive patients. Methods. Normotensives without [NT(−)] or with [NT(+)] familial predisposition and subjects with newly diagnosed hypertension (HT) were studied. Clinic blood pressure (BP) measurements and ambulatory BP monitoring as well as laboratory assessments were performed. Resting (RF), heat (HF) and maximal heat (MHF) blood flows were measured using PeriFlux laser Doppler flowmetry (LDF) and expressed as absolute units (AU) and as index of cutaneous vascular conductance (CVC). Spectral analysis of the skin LDF signal was performed by means of the Perisoft dedicated software. Kruskall–Wallis analysis of variance, χ2 statistic and multivariate reverse regression analysis were used for calculation. Results. The studied population consisted of 70 persons (mean age 36.1±10.3 years, 44.3% women): 17 NT(−), 22 NT(+) and 31 HT, age and gender matched. Higher values of body mass index (BMI), and insulin, glucose and triglyceride levels were observed in HT than in NT groups. RF, HF and MHF were similar in all study groups, but CVC of maximal heat flow differed (p=0.02); in particular, lower values were observed in the HT than in NT(−) group (p=0.01). The study groups differed with regard to total power (p=0.01) and myogenic (p=0.03) origin flowmotion with the lowest values in the NT(+) group. BMI and night BP characteristics were strong predictors of reduction of CVC, MHF and myogenic origin flowmotion. Conclusion. Skin microcirculation response to local heat stress is altered in hypertensive patients with decrease in maximal heat CVC values. Moreover, normotensive subjects with familial predisposition to hypertension are characterized by diminished myogenic origin of skin blood flowmotion.

Pointwise Hölder exponents of a model for skin laser Doppler flowmetry signals based on six nonlinear coupled oscillators with linear and parametric couplings: Comparison with experimental data from young healthy subjects

We study pointwise Hölder exponents of experimental and numerically simulated skin laser Doppler flowmetry (LDF) data that give a peripheral view of the cardiovascular system. The experimental signals are recorded in the forearm of young healthy subjects. The numerically simulated LDF data are computed from a model containing six nonlinear coupled oscillators reflecting six almost periodic rhythmic activities present in experimental LDF signals. Simulated LDF signals are for the first time generated with both linear and parametric couplings in order to represent cardiovascular system behaviors. Moreover, we propose the use of a parametric generalised quadratic variation (GQV) based estimation method for the estimation of the pointwise Hölder exponents. The latter identify possible multifractal characteristics of data. The GQV method is first tested on a white noise measure and then applied on the LDF data. The results of our signal processing analysis show that experimental LDF signals recorded in the forearm are weakly multifractal for young healthy subjects at rest. Furthermore, our findings show that the simulated data have a complexity similar to the one of signal recorded in young healthy subjects. However, their pointwise Hölder exponents have differences that we explain. This paper provides useful information to go deeper into the modeling of LDF data, which could bring enlightenment for a better understanding of the peripheral cardiovascular system.

ACTOVEGIN INFLUENCE ON METABOLIC AND VASOMOTOR FUNCTION OF MICROVASCULAR ENDOTHELIAL OF HUMAN SKIN

Aim. To evaluate effects of Actovegin (deproteinized hemoderivative) on vasomotor and metabolic functions of microvascular skin endothelium in healthy volunteers during acute pharmacological test. Material and methods. 24 healthy male volunteers, aged 18-26 years (21,9±2,7), received Actovegin i.v. during 2 hour infusion through the left cubital vein. Right forearm skin laser Doppler flowmetry (LDF) with wavelet analysis of the microcirculatory oscillations was used initially and after 2 hour Actovegin infusion to assess microvascular endothelial responses (microcirculatory blood flow changes) to Actovegin. Saline infusion in 5 subjects used for control data receiving. Results. Actovegin significantly increased in maximal amplitude endothelial rhythm (at a frequency of 0.01 Hz) by 76% (p&lt;0,001) and functional contribution of microvascular endothelium in the overall level of tissue perfusion by 79% (p&lt;0,001). Control saline infusion resulted in reduction of these indices by 52 and 54%, respectively. Actovegin also increased significantly myogenic rhythm amplitude (vascular tone reduction) by 35% (p&lt;0,05) and decreased diastolic blood pressure by 3 mm Hg (p=0,076), which is likely result of increased endothelium nitric oxide release. Conclusion. Microcirculatory oscillations at the frequency of 0.01 Hz reflect both vasomotor and metabolic function of microvascular endothelium. Actovegin improves oxygen and glucose tissue utilization as well as increases nitric oxide production with microvascular smooth muscle tone reduction.

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.

Study of skin vasomotion during phollicular and luteal phase in young healthy women

The aim of this study was to evaluate if changes in female sex hormones associated to follicular phase (FP) and luteal phase (LP) may affect skin vasomotion in women with evidence of ovulatory cycle. Nine healthy non-smoker women aged 25+/-4 years, with regular menstrual cycle of 28+/-2 days and evidence of ovulation (indicated by a mid-luteal serum progesterone concentration > 5 ng/ml) (group-1) and six healthy non-smoker healthy women aged 24+/-2 years with evidence of an-ovulatory cycle (group-2) were enrolled in the study. At the times 1 (7th-10th day from the beginning of the last menstrual cycle) and at the time 2 (18th-22th day from the beginning of the last menstrual cycle) forearm skin vasomotion was investigated by means of spectral Fourier analysis of the skin laser Doppler flowmetry (LDF) tracing registered under basal conditions and following acetylcholine (ACh) iontophoresis. The power spectral density (PSD) of the 0.01-0.02, 0.02-0.06 and 0.06-0.2 Hz LDF tracing frequency intervals (related to endothelial-, sympathetic- and myogenic-dependent vasomotion, respectively) was measured in PU2 (LDF perfusion unit)/Hz (1 PU = 10 mV). At the same times skin blood flux response (percentage change from baseline) to ACh and to sodium nitroprusside (SNP) iontophoresis was also investigated. Basal and ACh-stimulated skin vasomotion did not significantly differ between time 1 and time 2 in PSD of the three frequency intervals investigated in both groups, as well as between the two groups at each time of investigation. Similarly, no significant changes were observed in skin vasodilator response to ACh and SNP iontophoresis between time 1 and 2 in each group. These results suggest that the female sex hormone changes associated to the FP and LP in young women with ovulatory cycle do not affect basal and ACh stimulated skin vasomotion as well as the endothelial- and non-endothelial-dependent skin vasoreactivity.

Skin blood flowmotion and microvascular reactivity investigation in hypercholesterolemic patients without clinically manifest arterial diseases

Fourier spectral analysis of forearm skin laser Doppler flowmetry (LDF) signal was performed in fifteen hypercholesterolemic patients (HP), without clinically manifest arterial diseases, and in fifteen age-matched healthy control subjects (CS), in order to investigate skin blood flowmotion (SBF). The LDF frequency intervals studied were: 0.01-1.6 Hz total spectrum, as well as 0.01-0.02 Hz (endothelial), 0.02-0.06 Hz (sympathetic), 0.06-0.2 Hz (myogenic), 0.2-0.6 Hz (respiratory) and 0.6-1.6 Hz (cardiac). Skin microvascular reactivity (MVR) to acetylcholine (ACh) and to sodium nitroprusside (SNP) iontophoresis was also investigated. HP showed a lower post-ACh increase in power spectral density (PSD) of the 0.01-0.02 Hz SBF subinterval compared to CS (1.80+/-1.73 PU(2)/Hz vs 3.59+/-1.78 PU(2)/Hz, respectively; p<0.005), while they did not differ in MVR from CS. In eleven HP the 0.01-0.02 Hz SBF subinterval showed a higher post-ACh PSD increase near to the statistical significance after 10 weeks of rosuvastatin therapy (10 mg/day) compared to pretreatment test (3.04+/-2.95 PU(2)/Hz vs 1.91+/-1.94 PU(2)/Hz; p=0.07). The blunted post-ACh increase in PSD of the 0.01-0.02 Hz SBF subinterval in HP suggests a skin endothelial dysfunction in these patients. This SBF abnormality showed a tendency to improve after rosuvastatin therapy in eleven treated patients.

Abnormalities of Microcirculation and Intracranial and Cerebral Perfusion Pressures in Severe Brain Injury

Objective: to evaluate the states of microcirculation, cerebral perfusion intracranial pressures in patients with isolated severe brain injury (SBI) and to determine their possible relationships. Subjects and methods. 148 studies were performed in 16 victims with SBI. According to the outcome of brain traumatic disease, the patients were divided into two groups: 1) those who had a good outcome (n=8) and 2) those who had a fatal outcome (n=8). Microcirculation was examined by skin laser Doppler flowmetry using a LAKK-01 capillary blood flow laser analyzer (LAZMA Research-and-Production Association, Russian Federation). All the victims underwent surgical interventions to remove epi-, subdural, and intracerebral hematomas. A Codman subdural/intraparenchymatous intracranial pressure (ICD) sensor (Johnson &amp; Johnson, United Kingdom) was intraoperatively inserted in the victims. Cerebral perfusion pressure (CPP) was calculated using the generally accepted formula: CPP = MBP (mean blood pressure) — ICD. ICD, CPP, and microcirculation were studied on postoperative days 1, 3, 5, and 7. Their values were recorded simultaneously. Ninety and 58 studies were conducted in the group of patients with good and fatal outcomes, respectively. Results. No correlation between the changes in MBP, ICD, and microcirculatory parameters suggested that the value of ICD was determined by the nature of brain damage and it was the leading and determining indicator in the diagnosis and treatment of secondary cerebral lesions. The amplitude of low-frequency fluctuations directly correlated with ICD, which indicated that they might be used to evaluate cerebral perfusion and impaired cerebral circulation indirectly in victims with severe brain injury. Conclusion. The laser Doppler flowmetric technique makes it possible not only to qualitatively, but also quantitatively determine changes in the tissue blood flow system in severe brain injury. With this technique, both the local and central mechanisms which are responsible for changes in tissue blood flow autoregulation suffer, with a preponderance of the latter mechanisms. Key words: microcirculation, intracranial pressure, cerebral perfusion pressure, severe brain injury.