Reproducibility of near-infrared spectroscopy parameters measured during brachial artery occlusion and reactive hyperemia in healthy men

Near-infrared spectroscopy (NIRS) is a noninvasive technique evaluating microvascular function. The aim of this study was to assess the reproducibility of NIRS parameters during reactive hyperemia induced by a 5 min brachial artery occlusion. Twenty-four healthy young males (mean 34±8 years old) had two microvascular function evaluations by NIRS over a 7 to 30-day period (mean 16±10 days). Intra-subject and inter-observer reproducibility were evaluated with intraclass correlation coefficient (ICC), coefficient of variation (CV), and standard error of measurement (SEM%) for every parameter. Mean NIRS parameters did not differ between both evaluations. Reproducibility was greatest for muscle oxygen consumption (ICC: 0.84; CV: 6.51%; SEM: 7.11%), time to basal O(2)Hb (ICC: 0.63, CV: 20.04%, SEM 27.22%), time to maximal O(2)Hb (ICC: 0.71; CV: 15.61%; SEM: 19.27%), peak of O(2)Hb (ICC: 0.63, CV: 6.68%, SEM 8.53%), time to maximal tHb (ICC: 0.73, CV: 19,61%, SEM 24.56%) and area under the O(2)Hb and tHb curves (ICC: 0.68, CV: 16.15%, SEM 22.93% and ICC: 0.62, CV: 18.59%, SEM 26.64%, respectively). Moreover, inter-observer reproducibility ranged from excellent to perfect (ICC from 0.85 to 1.00) for every parameter. NIRS parameters during reactive hyperemia are highly reproducible which enables their repeated measurement to study microvascular function in healthy subjects.     

Dynamic microvascular blood flow analysis during post-occlusive reactive hyperemia test in patients with schizophrenia

Patients suffering from schizophrenia have an increased mortality risk due to cardiovascular events. Recently the analysis of peripheral circulation has revealed interesting results in the study of vascular pathological conditions assuming that the state of microcirculation of the skin is at least partly representative for the constitution of other vascular beds including those of the cardiac muscle and arteries. The objective of this study was to investigate the microcirculation in patients with acute schizophrenia (PAT, n = 15, mean age 33.0 years, 7 male, 8 female) to identify whether spectral features from blood flow signals derived through laser Doppler spectrometry are significantly altered compared to healthy subjects (CON, n = 15, mean age 32.4 years, 7 male, 8 female) by means of the post-occlusive reactive hyperemia test. It was also explored if a segmentation of the post-ischemic stage can disclose more detailed and additional information about the dynamic behavior of the blood flow during hyperemic response. For this reason, time–frequency analyses were performed to observe the course of the blood flow frequency components over time. Our results indicate significant differences in the patients group, already detectable under baseline conditions but also in the hyperemic phase. The main modifications affect the respiratory (p = 0.006) as well as the cardiac (p = 0.001) activity. It was further shown that the application of a segmented analysis of the post-ischemic state considerably improves the differentiation between both groups. Only with the introduced segmentation algorithm using a window length of 2048 samples and a shift of 128 and 256 samples we could demonstrate influences of the disease on the endothelial (p = 0.029), the sympathetic (p = 0.019) and the myogenic (p = 0.029) mechanisms. These information provide further insights into the appearance of schizophrenia and could lead to an improvement of the patients’ treatment to avoid the occurrence of cardiovascular events.     

Reliability of near-infrared spectroscopy for measuring forearm and shoulder oxygenation in healthy males and females

This study determined the day-to-day reliability of NIRS-derived oxygenation responses (?StO(2)%) for isometric contractions and for cuff occlusion. Twenty-four subjects (12 males and 12 females) were tested for 2 days (4-6 days interval). Variables generated were: (1) ?StO(2)% for isometric contractions (10, 30, 50 and 70% MVC) for descending trapezius (TD) and extensor carpi radialis (ECR) muscles; (2) slope changes in total haemoglobin (HbTslope) and deoxyhaemoglobin (HHbslope) for the ECR using upper arm venous (VO, 50 mmHg) and arterial occlusion (AO, 250 mmHg); (3) recovery slopes (Rslope) for oxygen saturation (StO(2)) following isometric contractions and AO. For each variable, an intraclass correlation (ICC) was calculated to assess the ability to differentiate between subjects, and limits of agreement (LOA) were computed to assess day-to-day consistency of the measurement. ICCs for ΔStO(2)% were lowest at 10% MVC for both ECR (0.58) and TD (0.55), and highest at 30% MVC for ECR (0.95) and at 70% MVC for TD (0.79). For both muscles, LOA for ΔStO(2)% was lowest at 10% and highest at 50 and 70% MVC. ICC for HbTslope was 0.17. For HHbslope ICC was higher for AO (0.83) than for VO (0.73), and LOA was lower for AO. For the ECR Rslope ICCs ranged from 0.88 to 0.90 for contraction, but was lower for AO (0.33); LOA was lowest at 70% MVC. For trapezius Rslope ICCs ranged from 0.63 to 0.73 and LOA was lowest at 30% MVC. For this study, establishing reliability data for the ECR and TD and including variables commonly reported are expected to have meaning for future NIRS studies of work-related upper-extremity pain as well as for other NIRS research and clinical applications.     

Characterizing reactive hyperemia via tissue reflectance spectroscopy in response to an ischemic load across gender,age, skin pigmentation and diabetes

Purpose: Pressure ulcers represent a major secondary complication for amputees with diabetes and further complications may arise since ulcers are particularly hard to heal in this population. This study characterized the hyperemic response to a localized ischemic load in people with diabetes and amputation and compared it to that of subjects without diabetes or amputation. Subjects: Case-control study matching subjects by gender, age, skin pigmentation, and smoking status. Methods: Applying 150 mmHg to the patellar tendon for 10 minutes induced reactive hyperemia (RH). Tissue reflectance spectroscopy measured hemoglobin (HbO₂) concentration in tissue before, during and after application of pressure. Refill time, Maximum HbO₂, Time@Max HbO₂, RH area and RH half-life characterized the RH response and were analyzed using ANOVA. All values up to a level of p <0.1 are presented. Results: Analysis included responses from 88 subjects. RH magnitude and temporal parameters varied across skin pigmentation; smokers showed a decreased RH magnitude; vasodilator users had greater RH temporal parameters; no evidence of differences were found across disease state or age. Conclusion: Decreased RH response in smokers and subjects with dark skin might indicate a reduced ability to recover from ischemia. The lack of difference in RH response between subjects with and without diabetes was consistent with studies using other disability groups and corroborates the theory that RH is locally mediated.     

Tissue oxygenation measured with near-infrared spectroscopy during normobaric and hyperbaric oxygen breathing in healthy subjects

To evaluate the possibility of using near-infrared spectroscopy (NIRS) to measure tissue oxygenation (StO₂) during hyperbaric oxygen (HBO) therapy. Nine healthy volunteers (1 female) age 25−37 years, breathed air or oxygen. Tissue oxygenation was measured using NIRS on the thumb. Subjects were blinded to breathing gas. A range of partial pressures of oxygen were administered in 10-min intervals: 21, 101, 21 kPa (compression to 280 kPa), 59, 280, 59 (decompression), 21 kPa. Data were averaged over last 5 min at each pressure. When switching from air to normobaric oxygen (NBO 101 kPa) StO₂ increased from 83% (82−85%, median and interquartile range) to 85% (84−87%) (P < 0.01), while when switching from air at pressure (59 kPa O₂) to HBO (280 kPa), StO₂ increased from 85% (85−86%) to 88% (87−89%) (P < 0.001). There was no difference between baseline StO₂ while air breathing before NBO or after decompression. Values did not reach the maximal value of 100% at any point. The changes in hemoglobin oxygen saturation in tissue registered by the NIRS monitor when switching from air to oxygen followed inspired PO₂ under normobaric and hyperbaric conditions.     

Right frontal activation during the continuous performance test assessed with near-infrared spectroscopy in healthy subjects

Near-infrared spectroscopy (NIRS) is a non-invasive optical technique which has been successfully used to register substantial cerebral ischemia. There are indications that NIRS is sensible enough to detect also small metabolic changes during the performance of cognitive tasks. In the present study, two-channel NIRS of left and right anterior frontal brain areas was applied to investigate brain oxygenation of 10 healthy subjects carrying out the continuous performance test (CPT). Significant differences between the left and right hemisphere were found. These consisted of different changes in deoxyhaemoglobin (HHB), but not in oxyhaemoglobin (O₂HB) in right frontal brain areas compared to baseline during the test. Despite of some methodological restrictions, the findings suggest that the sensitivity of the NIRS-method is sufficient to detect brain oxygenation changes during cognitive activation. Furthermore, the results support the view that execution of the CPT is associated with prevalently right frontal activation.     

Reliability of erector spinae oxygenation and blood volume responses using near-infrared spectroscopy in healthy males

The purpose of this investigation was to (1) describe the trends in oxygenation (OXY) and blood volume (BV) of the right and left paraspinal muscles during the Biering-Sorensen muscle endurance (BSME) test using near infrared spectroscopy (NIRS), and (2) assess the test-retest reliability of OXY and BV changes during the BSME in healthy males. Seventeen healthy males [age=28.4 (9.8) years, height=1.75 (0.05) m, body mass=82.7 (9.1) kg; mean (SD)] completed two BSME trials within 1 week. NIRS probes were placed bilaterally at lumbar 3. The test was performed with the subject in the prone position using the following protocol: 2 min baseline, BSME, and 4 min recovery. The delta and range values of OXY and BV were used for analysis. Acceptable intra-class correlations were observed for endurance time and all the NIRS variables at the point of fatigue and at each 10% segment of the BSME during the two trials. Bland-Altman plots confirmed the reproducibility of the bilateral NIRS responses of the paravertebral muscles. The BV responses were more reliable than the OXY responses during the two trials. The OXY and BV responses of the paravertebral muscles during static contractions can be measured reliably using NIRS. Future studies should focus primarily on BV for analysis.     

Decreased cortical reactivity underlies subjective daytime light sleepiness in healthy subjects: a multichannel near-infrared spectroscopy study

Daytime sleepiness is considered to be one of the main problems in modern society. Of the four aspects of sleepiness, namely, subjective sleepiness, performance decrease, sleep propensity, and arousal decrease, subjective sleepiness is the most difficult to assess. Brain mechanisms underlying subjective light sleepiness in daytime were investigated in healthy subjects using multichannel near-infrared spectroscopy (NIRS), which enables the noninvasive measurement of regional cerebral blood volume (rCBV) changes under natural conditions. Forty right-handed healthy volunteers participated in this study. Relationships were investigated between subjective sleepiness and anxiety, assessed using the Stanford Sleepiness Scale (SSS) and State-Trait Anxiety Inventory (STAI), respectively, and cerebral cortex reactivities assessed as oxygenated and deoxygenated hemoglobin concentration ([oxy-Hb] and [deoxy-Hb], respectively) changes during a verbal fluency task using a 24-channel NIRS machine. SSS score correlated negatively with an [oxy-Hb] increase in the bilateral frontal channels mainly in the middle and last third of the verbal fluency task period. Subjective light daytime sleepiness in healthy subjects is considered to be related to decreased prefrontal reactivities in the later part of cognitive activation.     

Reduced reactive hyperemia in HIV-infected patients

BACKGROUND: Given that several pathology-based studies reported some degree of coronary and arterial vasculopathy in HIV-infected patients, we investigated whether abnormal vascular reactivity may also be found in these patients. METHODS: Vascular reactivity was assessed noninvasively using finger-skin blood-flow monitoring by laser-Doppler flow measurement in 10 HIV-infected-patients (mean CD4 T-cell count, 350+/-84 cells/mm3) with cardiac symptoms (previous myocardial infarction or left-ventricular dysfunction) and/or HIV-related protease inhibitor-induced hyperlipemia (group 1, symptomatic), 19 HIV-infected patients free of cardiac disease, hyperlipemia, and previous opportunistic infections (mean CD4 T-cell count, 333+/-175 cells/mm3; group 2, asymptomatic), and 19 healthy control subjects (group 3). Laser-Doppler flow was measured at baseline, during postocclusive hyperemic response following transient interruption of brachial blood flow (reactive hyperemia), during transcutaneous delivery of acetylcholine (Ach) using iontophoresis (endothelium-dependent dilation) and after sublingual nitroglycerin administration (endothelium-independent dilation). RESULTS: During reactive hyperemia, the absolute increase in flow was found to be lower in asymptomatic HIV-infected patients than in controls (median values [25th-75th percentile]: asymptomatic: 300 [200-400]; versus controls: 600 [400-750] arbitrary units [AU]; p< or =.0001). This abnormality was more pronounced in symptomatic patients (100 [100-200]; p< or =.0001). There was also a reduced peak/baseline flow ratio (symptomatic: 1.14 [1.1-1.2]; asymptomatic: 1.40 [1.25-1.5]; versus controls: 1.83 [1.6-2.2]; p<.0001 for both comparisons) and a reduced hyperemic response, as assessed by the curve of area under the flow versus time from deflation to the end of the hyperemic response (symptomatic: 1850 [1100-2225]; asymptomatic: 6000 [2850-7950]; versus controls: 23,735 [16,000-31, 800] AU x sec; p<.0001 for both comparisons). Although there was no statistically significant difference in acetylcholine (Ach)-induced increases in flow between asymptomatic HIV patients and controls (peak/baseline flow ratio: 6 [4.4-10] versus 5.3 [4-8]; p =.47), a trend to lower values was seen in symptomatic patients (4.4 [1.2-5]; p =.06). Administration of 0.4 mg sublingual nitroglycerin resulted in increases in flow without statistically significant difference between patients and controls: peak/baseline flow ratio for symptomatic: 2.4 [1.9-2.7]; asymptomatic: 2.1 [1.75-2.34] versus controls: 1.97 [1.8-2.4]; p =.2 and.83, respectively). CONCLUSIONS: Postischemic reactive hyperemia is reduced in HIV-infected patients. In addition, there was is trend for a reduced response to Ach only in those with cardiac disease and/or hyperlipemia.     

Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects

The major predisposing factor for melioidosis is diabetes mellitus, but no immunological mechanisms have been investigated to explain this. In this study, polymorphonuclear neutrophil (PMN) responses to Burkholderia pseudomallei, the causative agent of melioidosis, in healthy and diabetic Thai subjects were determined by flow cytometry. The results showed that B. pseudomallei displayed reduced uptake by PMNs compared to Salmonella enterica serovar Typhimurium and Escherichia coli. Additionally, intracellular survival of B. pseudomallei was detected throughout a 24-h period, indicating the intrinsic resistance of B. pseudomallei to killing by PMNs. Moreover, PMNs from diabetic subjects displayed impaired phagocytosis of B. pseudomallei, reduced migration in response to interleukin-8, and an inability to delay apoptosis. These data show that B. pseudomallei is intrinsically resistant to phagocytosis and killing by PMNs. These observations, together with the impaired migration and apoptosis in diabetes mellitus, may explain host susceptibility in melioidosis.     

Correct and erroneous picture naming responses in healthy subjects

In this functional magnetic resonance imaging study, brain activations of correct and erroneous picture naming responses were investigated in 34 healthy subjects using an event-related design. We regarded main effects comprising all (ALL), false (FAL), or correct (COR) responses only. Despite the rare error occurrence, activation maxima differed between all three main effects. To investigate the influence of naming accuracy on brain activations, we therefore (1) considered the number of errors as covariates, and (2) compared carefully matched sets of FAL and COR for subjects with higher error rates. As a result, activations in left middle/medial frontal gyrus were significantly correlated with number of errors. The neural substrate of naming errors appears to be separated in several subsystems of activation: first bilateral activations in anterior cingulate cortex (ACC), prefrontal, and premotor regions associated with monitoring processes; second the involvement of right (para)hippocampal gyrus most likely indicating post-error processes of retention; third perisylvian (especially inferior frontal) language areas. These activations were not restricted to false responses, but were with less intensity also recruited for correct responses. In contrast, there was no specific activation for successful name retrieval in correct trials. To conclude, the underlying processing mechanisms of erroneous and correct naming responses are strikingly similar; self-monitoring appears to be a general mechanism of the naming process.     

Dynamics of swallowing-induced cardiac chronotropic responses in healthy subjects

Simultaneous recording of ECG and swallowing movements in healthy humans (n=23, age 20-57 years) showed that each swallow is accompanied by transient tachycardia with initial abrupt and pronounced heart rate increase. These rapid changes in heart rate (evaluation by maximum increment of heart rate over two successive heartbeats, HR_2bt) are typical of vagal chronotropic responses. The amplitude of tachycardia induced by a single swallow was significantly higher in the supine position (13.1±5.6 bpm) compared to the standing position (8.5±3.8 bpm; p<0.0001). Chronotropic responses to a series of three or more successive swallows consisted of two phases, the initial abrupt acceleration and subsequent slower growth of heart rate. In the standing position, the portion of the first rapid phase significantly decreased, while the portion of the slower phase increased compared to the supine position. The amplitude of tachycardia induced by a single swallow and parameter HR_2bt can serve as indices of the strength of parasympathetic modulation of the heart. By contrast, further slow increase in the heart rate determined by summation of responses to a series of successive swallows can result from not only inhibition of the parasympathetic influences, but also enhancement of sympathetic activity during swallowing.     

A study on the role of endogenous prostaglandins in the development of exercise-induced and post-occlusive hyperemia in human limbs

The contribution of endogenous PGs to the development of functional (exercise-induced) and reactive (post-occlusive) hyperemia was investigated in healthy volunteers. Leg blood flow during dynamic leg exercise was estimated by an indicator dilution technique. Forearm blood flow during supine leg exercise and forearm and calf blood flow following 5 min of arterial occlusion were measured plethysmographically. All subjects were examined before and after pretreatment with indomethacin, a PG synthesis inhibitor. During leg exercise, and in the absence of indomethacin, a 10-fold rise in leg blood flow was observed. Forearm blood flow increased moderately. Both these blood flow effects of exercise were unaffected by indomethacin. Following arterial occlusion a marked hyperemia developed in the forearm and the calf. Indomethacin significantly reduced the magnitude of the reactive hyperemia both in the forearm and in the calf, decreasing both the peak value and the duration of the vasodilation. These data reveal differences between the mechanisms behind functional and reactive hyperemia in man, suggesting an appreciable contribution of endogenous PGs to post-occlusive vasodilation only.     

Multiple-time replicability of near-infrared spectroscopy recording during prefrontal activation task in healthy men

Near-infrared spectroscopy (NIRS) has the potential for clinical application in neuropsychiatry because it enables non-invasive and convenient measurement of hemodynamic response to cognitive activation. Using 24-channel NIRS in 12 healthy men, we examined the replicability of oxy- and deoxy-hemoglobin concentration ([oxyHb], [deoxyHb]) changes in the prefrontal cortex during the category fluency task over four repeated sessions (each 1-week apart). Multiple methods were employed to evaluate the replicability of magnitude, location, and time course of the NIRS signals ([oxyHb], [deoxyHb]). Task performances did not differ significantly across sessions, nor were they significantly correlated with NIRS signals. Repeated measures ANOVA and variance component analysis indicated high replicability of magnitude for both NIRS measures, whereas the effect sizes of between-session differences in [oxyHb] were not negligible. The number and spatial location of significantly activated channels were sufficiently replicable for both measures, except that the across-session overlap of significantly activated channels was weak in [deoxyHb]. The time course of the activation was acceptably replicable in both measures. Taken together, these findings suggest there is considerable replicability of multiple-time measurements of prefrontal hemodynamics during cognitive activation in men. Further studies using different conditions or assessing sensitivity to longitudinal changes following interventions are necessary.     

Plasma vasopressin,growth hormone and ACTH responses to static handgrip in healthy subjects

Summary Ten healthy male subjects took part in the study. They performed three consecutive bouts of static handgrip at 30% of maximal voluntary contraction (MVC), using two hands alternately and without rest intervals. Blood pressure was measured every 30 s and ECG was recorded continuously. Blood samples for arginine vasopressin (AVP), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and cortisol determinations were taken at rest, after each exercise bout, as well as at 10 and 30 min after the last one. During the whole period of exercise (9 min) blood pressure and heart rate were elevated. The effort caused a significant increase in the plasma AVP concentration. In the majority of subjects the peak values occurred after the first or second exercise bout and were followed by a rapid decline of the hormone concentration. Changes in GH, ACTH and cortisol concentrations were insignificant; however, in seven of the ten subjects, considerably elevated plasma GH levels were found at the end of the third exercise bout and/or 10 min after its cessation.