BACKGROUND: Post-occlusive reactive hyperemia (PORH) test with signal spectral analysis coupled provides potential indicators for the assessment of microvascular functions.
OBJECTIVE: The objective of this study is to investigate the variations of skin blood flow and temperature spectra in the PORH test. Furthermore, to quantify the oscillation amplitude response to occlusion within different frequency ranges.
METHODS: Ten healthy volunteers participated in the PORH test and their hand skin temperature and blood flow images were captured by infrared thermography (IRT) and laser speckle contrast imaging (LSCI) system, respectively. Extracted signals from selected areas were then transformed into the time-frequency space by continuous wavelet transform for cross-correlation analysis and oscillation amplitude response comparisons.
RESULTS: The LSCI and IRT signals extracted from fingertips showed stronger hyperemia response and larger oscillation amplitude compared with other areas, and their spectral cross-correlations decreased with frequency. According to statistical analysis, their oscillation amplitudes in the PORH stage were obviously larger than the baseline stage within endothelial, neurogenic, and myogenic frequency ranges (p < 0.05), and their quantitative indicators of oscillation amplitude response had high linear correlations within endothelial and neurogenic frequency ranges.
CONCLUSIONS: Comparisons of IRT and LSCI techniques in recording the reaction to the PORH test were made in both temporal and spectral domains. The larger oscillation amplitudes suggested enhanced endothelial, neurogenic, and myogenic activities in the PORH test. We hope this study is also significant for investigations of response to the PORH test by other non-invasive techniques.

Microcirculation in vivo has been assessed using non-invasive technologies such as laser Doppler flowmetry (LDF). In contrast to chronic hyperglycemia, known to induce microvascular dysfunction, the effects of short-term elevations in blood glucose on microcirculation are controversial. We aimed to assess the impact of an oral glucose load (OGL) on the cutaneous microcirculation of healthy subjects, quantified by LDF and coupled with wavelet transform (WT) as an interpretation tool. On two separate occasions, sixteen subjects drank either a glucose solution (75 g in 250 mL water) or water (equal volume). LDF signals were obtained in two anatomical sites (forearm and finger pulp) before and after each load (pre-load and post-load, respectively), in resting conditions and during post-occlusive reactive hyperemia (PORH). The WT allowed decomposition of the LDF signals into their spectral components (cardiac, respiratory, myogenic, sympathetic, endothelial NO-dependent). The OGL blunted the PORH response in the forearm, which was not observed with the water load. Significant differences were found for the cardiac and sympathetic components in the glucose and water groups between the pre-load and post-load periods. These results suggest that an OGL induces a short-term subtle microvascular impairment, probably involving a modulation of the sympathetic nervous system.

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide. Methods: This substudy to the open-label phase II trial \"Cyclophosphamide in ME/CFS\" included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18-65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30). Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5-13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7-21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343-4,334) vs. healthy individuals 1,886 p.u. (range 808-8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls. Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.

BACKGROUND: Existing techniques for assessment of microcirculation are limited by their large size and high costs and are often not so easy to use. Advances in mobile technology have enabled great improvements in smartphone sensor technology. In this study, we used SkinSight, an app for iPhone and iPad, to measure changes in skin microcirculation during physiological provocations. The system estimates changes in the concentration of hemoglobin in the skin by analyzing the reflected light emitted from the built-in light-emitting diode and detected by the camera of the smartphone.
METHODS: A relative hemoglobin (Hb) index was measured during a 5-min arterial occlusion, post-occlusive reactive hyperemia, and a 5-min venous occlusion in 10 healthy subjects, on two separate days. The index was calculated in an area of the skin from the color information in the images acquired by the phone camera. Polarized light spectroscopy imaging was used to measure changes in red blood cell concentration for comparison.
RESULTS: During arterial occlusion, relative Hb index was unchanged compared to baseline (P = .40). After release of the cuff, a sudden 60%-75% increase in Hb index was observed (P < .001) followed by a gradual return to baseline. During venous occlusion, Hb index increased by 80% (P < .001) followed by a gradual decrease to baseline after reperfusion. Day-to-day reproducibility of the relative Hb index was excellent (ICC: 0.92, r = 0.94), although relative Hb index was consistently higher during the second day, possibly as a result of changed lighting conditions or calibration issues.
CONCLUSIONS: Microvascular responses to physiological provocations in the skin can be accurately and reproducibly measured using a smartphone application. Although the system offers a handheld, easy to use and flexible technique for skin microvascular assessment, the effects of lighting on the measured values and need for calibration need to be further investigated.

Although increasing studies indicate coronary slow flow (CSF) is a systemic microvascular disorder, whether there is impaired cutaneous microvascular endothelial function in CSF patients remains unclear. This study was designed to test the hypothesis that the cutaneous microvascular endothelial function of CSF patients is impaired and correlates with lectin-like oxidized low-density lipoprotein receptor-1(LOX-1).
39 patients with CSF and 45 controls with normal coronary flow were enrolled. Velocity of coronary flow was quantitatively identified by thrombolysis in myocardial infarction frame count (TFC) method. LSCI system was used to assess subjects\' cutaneous blood flow at rest and during PORH. Serum soluble LOX-1(sLOX-1) level was measured in all study subjects.
PORH-induced vasodilation was significantly reduced in CSF group in comparison with control group (0.26 ± 0.10 vs 0.35 ± 0.07 APU/mmHg, P < 0.001) and negatively correlated with the mean TFC for three coronary arteries (r = -0.385, P = 0.016). Serum sLOX-1 level in CSF group was significantly increased (582.93 ± 74.89 vs 483.64 ± 51.38 pg/ml, P < 0.001) and positively correlated with mean TFC(r = 0.467, P = 0.003).PORH response amplitudes had a significantly negative relationship with serum sLOX-1 level in CSF patients (r = -0.588, P < 0.001).
These data suggest that cutaneous microvascular endothelial function is impaired in patients with CSF, which is closely associated with increased LOX-1 expression.

To assess changes of post-occlusive reactive hyperemic response in skin microcirculation among extremely obese patients 10 days and 6 months after bariatric surgery for patients with and without hypertension.
Skin blood flow was measured using PeriFlux laser Doppler fluxmetry. Data were analyzed in the entire group and two subgroups: with and without hypertension.
Data from 88 patients (mean age 42.1 ± 11.2 years, 40.5% men) were analyzed. Six months after bariatric surgery, the time to reach peak flows had been shortened (2.4 ± 1.7 vs 2.1 ± 1.0 seconds, P < .05) and the area of hyperemia had increased (1027 ± 791 vs 1386 ± 699 AU*s, P < .05). The total power of post-occlusive reactive hyperemic after occlusion had been augmented mainly with power intensification of endothelial and myogenic origin. Post-occlusive reactive hyperemic parameters had changed mainly in the subgroup with hypertension. Variations of anthropometric parameters, metabolic characteristic, and adipokines mainly influenced on studied hyperemic flow parameters variations after the intervention in multiple regression analysis.
Cutaneous post-occlusive reactive hyperemic reactivity in time and frequency domains improved 6 months after bariatric surgery, and improvements in microvascular function were observed mainly in patients with hypertension. Variations of anthropometric parameters, metabolic characteristics, and adipokines had influence on hyperemic flow reactivity.

OBJECTIVE: Laser Doppler imaging (LDI) and laser speckle imaging (LSI) are two major optical techniques aiming at non-invasively imaging the skin blood perfusion. However, the relationship between perfusion values determined by LDI and LSI has not been fully explored.
METHODS: 8 healthy volunteers and 13 PWS patients were recruited. The perfusions in normal skin on the forearm of 8 healthy volunteers were simultaneously measured by both LDI and LSI during post-occlusive reactive hyperemia (PORH). Furthermore, the perfusions of port wine stains (PWS) lesions and contralateral normal skin of 10 PWS patients were also determined. In addition, the perfusions for PWS lesions from 3 PWS patients were successively monitored at 0, 10 and 20min during vascular-targeted photodynamic therapy (V-PDT). The average perfusion values determined by LSI were compared with those of LDI for each subject.
RESULTS: In the normal skin during PORH, power function provided better fits of perfusion values than linear function: powers for individual subjects go from 1.312 to 1.942 (R(2)=0.8967-0.9951). There was a linear relationship between perfusion values determined by LDI and LSI in PWS and contralateral normal skin (R(2)=0.7308-0.9623), and in PWS during V-PDT (R(2)=0.8037-0.9968).
CONCLUSIONS: The perfusion values determined by LDI and LSI correlate closely in normal skin and PWS over a broad range of skin perfusion. However, it still suggests that perfusion range and characteristics of the measured skin should be carefully considered if LDI and LSI measures are compared.

BACKGROUND: Post-occlusive reactive hyperaemia (PORH) is a measurement of the vasodilatory capacity of the microvasculature that is associated with cardiovascular disease, peripheral arterial disease and foot ulceration. The reliability of its measurement in the hallux (great toe) for clinical and research purposes has not been adequately assessed. This study assesses both the intra-tester reliability and inter-tester reliability of four methods of assessing PORH in the hallux.
RESULTS: A within-subject repeated measures design was used. Forty-two participants underwent PORH testing using four methods: pressure measurement with photoplethysmography; an automated laser Doppler technique with local heating; an automated laser Doppler technique without local heating; and a manual laser Doppler technique. Participants underwent testing on two occasions with a three to 14 day interval. Laser Doppler measurement with a heating probe was found to be the most reliable method of PORH measurement. The index of the area under the curve pre- and post-occlusion and peak perfusion as a percentage of baseline were the most reliable variables.
CONCLUSIONS: PORH can be reliably measured using laser Doppler when combined with a heating probe. Further research is required to determine the clinical utility of photoplethysmography in the measurement of PORH.

OBJECTIVE: Postocclusive reactive hyperemia is mediated by two major mediators: sensory nerves and endothelium-derived hyperpolarizing factors. We hypothesized that the skin microvascular response to 5 min ischemia would differ depending upon the hand location in patients with systemic sclerosis (SSc), primary Raynaud\'s phenomenon (PRP) and healthy controls.
METHODS: Fifteen patients with SSc, 15 sex- and age-matched patients with PRP and healthy controls were enrolled. Their right hands were subjected to 5 min ischemia followed by a postocclusive hyperemia test, with local microcirculation monitoring by laser speckle contrast imaging on the dorsal face of the hand.
RESULTS: Postocclusive reactive hyperemia was abnormal in terms of peak and area under the curve (AUC) on all fingers except the thumb in patients with SSc and PRP compared with controls. In contrast, the kinetics of the response was longer only in SSc patients, with mean (SD) time to peak on the index, middle and ring finger were respectively 72 (58), 73 (51) and 67 (47) s for SSc; 40 (20), 40 (20) and 36 (19) s for PRP; and 34 (30), 34 (30) and 29 (24) s for controls (P=0.009 for interaction).
CONCLUSIONS: We observed decreased distal digital microvascular perfusion following 5 min of ischemia in patients presenting with PRP or SSc, while the kinetics was prolonged only in SSc. A dynamic assessment of digital skin blood flow using laser speckle contrast imaging following 5 min ischemia could be used as a tool to assess microvascular abnormalities in patients with Raynaud\'s phenomenon secondary to SSc.

The present study was undertaken to determine the effect of arterial blood hypoxemia induced by acute systemic hypoxia (pO2=12%) on capillary recruitment and diameter, and red blood cell (RBC) velocity in human nail fold capillaries during rest, arterial post-occlusive reactive hyperemia (PRH), and venous occlusion (VO) using intravital video-capillaroscopy. Capillary recruitment was unchanged in acute systemic hypoxia (H) versus normoxia (N). There was no difference in RBC velocity measurements between normoxia and hypoxia (P<0.63). However, a statistically significant increase in nail fold capillary total width (N, 39.9±9.1 vs. H, 42.7±10.3 μm; P<0.05), apical diameter (N, 15.5±4.3 vs. H, 16.8±4.3 μm; P<0.05), arterial diameter (N, 11.9±3.5 vs. H, 13.9±4.1 μm; P<0.05), and venous diameter (N, 15.5±4.3 vs. H, 17.2±4.8 μm; P<0.05) was observed and continued to be significant most often during post-occlusive reactive hyperemia (PRH) and venous congestion (VO). These data suggest that acute systemic hypoxia does not increase capillary recruitment, but instead increases capillary diameter, resulting in increased capillary blood flow.