Plethysmographic Measurements Research Articles

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.

Improved FPGA controlled artificial vascular system for plethysmographic measurements

Abstract The fetal oxygen saturation is an important parameter to determine the health status of a fetus, which is until now mostly acquired invasively. The transabdominal, fetal pulse oximetry is a promising approach to measure this non-invasively and continuously. The fetal pulse curve has to be extracted from the mixed signal of mother and fetus to determine its oxygen saturation. For this purpose efficient algorithms are necessary, which have to be evaluated under constant and reproducable test conditions. This paper presents the improved version of a phantom which can generate artificial pulse waves in a synthetic tissue phantom. The tissue phantom consists of several layers that mimic the different optical properties of the fetal and maternal tissue layers. Additionally an artificial vascular system and a dome, which mimics the bending of the belly of a pregnant woman, are incorporated. To obtain data on the pulse waves, several measurement methods are included, to help understand the behavior of the signals gained from the pulse waves. Besides pressure sensors and a transmissive method we integrated a capacitive approach, that makes use of the so called “Pin Oscillator” method. Apart from the enhancements in the tissue phantom and the measurements, we also improved the used blood substitute, which reproduces the different absorption characteristics of fetal and maternal blood. The results show that the phantom can generate pulse waves similar to the natural ones. Furthermore, the phantom represents a reference that can be used to evaluate the algorithms for transabdominal, fetal pulse oximetry.

Intraindividual Variability in Test-Retest Air Displacement Plethysmography Measurements of Body Density for Men and Women.

Air displacement plethysmography (ADP) is a popular method for estimating body density (Db). Most ADP tests are performed once, with test-retest investigations scarce. Therefore, we investigated test-retest reliability of ADP. Active men (n = 25) and women (n = 25) volunteered and followed standard pretest guidelines. Participants wore dry, form-fitting swimwear and manufacturer-supplied swim caps. In a single session, two ADP trials with measured thoracic gas volume (TGV) were performed without repositioning participants. Separate 2 (sex) × 2 (ADP trial) repeated-measures ANOVAs were performed to investigate within-between comparisons of Db, TGV, body volume (Vb), and relative fatness (%BF). Paired t tests were used to investigate significant differences as appropriate. The Bland and Altman technique was used to depict individual intertrial variations. For all analyses, α =.05. A significant main effect for sex was found; men were lower in %BF and higher in all other variables compared with women. Individual variability was notable (ADP1-ADP2). The range of individual intertrial differences were larger for women than men, respectively, for Db (-0.0096-0.0045 g/cc; -0.0019-0.0054 g/cc), TGV (-0.623-1.325 L; -0.584-0.378 L), Vb (-0.249-2.10 L; -0.234-0.397 L), and %BF (-2.1-4.4%; -0.2-0.9%). When assessing body composition of women via ADP or using Db from ADP in a multicomponent model, at least two trials with measured TGV should be performed and the average of the values recorded and reported.

ТЕОРЕТИЧЕСКИЕ И МЕТОДИЧЕСКИЕ АСПЕКТЫ БОДИПЛЕТИЗМОГРАФИИ И ЕЕ КЛИНИЧЕСКОЕ ПРИМЕНЕНИЕ

One of the methods to evaluate lung function is body plethysmography. Body plethysmography allows to measure indicators that cannot be obtained during spirometry, that is: total lung capacity (TLC), bronchial resistance (Raw), and functional residual capacity (FRC). FRC measured by body plethysmography reflects thoracic gas volume (TGV or VTG), and includes both ventilated and poorly ventilated volume. Plethysmographic measurements are based on the principle of the relationship between pressure and volume at constant temperature and fixed amount of gas. This principle states that the absolute pressure exerted by a given mass of an ideal gas is inversely proportional to the volume it occupies if the temperature and amount of gas remain unchanged within a closed system (Boyle-Mariotte Law). In body plethysmography, the following parameters: TGV, vital capacity (VC), expiratory reserve volume (ERV), tidal volume (TV), inspiratory reserve volume (IRV), inspiratory capacity (IC), Raw are obtained. TLC, residual volume (RV) and its share in total lung capacity can be calculated. Reduced TLC allows to diagnose restrictive disorders of pulmonary ventilation. The RV and its share in TLC increase together with airway obstruction indicates air trapping. The TGV increase together with airway obstruction indicates hyperinflation. In the analysis of lung volumes predictive values, which are calculated by the formulas recommended by ATS/ERS statement, are used. The results are expressed as a percentage of the predicted value. Thus, body plethysmography is an important addition to spirometry and image methods of research, allowing to assess the functional state of the lungs more objectively; it helps to conduct the differential diagnosis and control the course of the disease.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma.

Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary (1)H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary (1)H MRI. Therefore, their objective was to develop a pulmonary (1)H MRI segmentation algorithm to provide regional measurements with the precision and speed required to support clinical studies. The authors developed a method to segment the left and right lung from (1)H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as (1)H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, (1)H MRI was resampled into ∼3 × 3 × 3 mm(3) isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary (1)H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was 83% ± 7% and FEV1 was 86 ± 9%pred. For 15 severe, poorly controlled asthmatics, FEV1/FV C = 66% ± 17% and FEV1 = 72 ± 27%pred. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.

Long Term Endurance Exercise Training Ameliorates Conduit Artery Retrograde and Oscillatory Shear in Older Adults

With aging, there tends to be an increase in retrograde and oscillatory shear in peripheral conduit arteries of humans. Whether the increase in shear rate is due to the aging process or an effect of a less than active lifestyle that often accompanies aging is unknown. Therefore, in a cross‐sectional study we evaluated whether chronic endurance exercise training attenuates retrograde and oscillatory shear in older adults. Brachial and common femoral artery mean blood velocities and diameter were determined via Doppler ultrasound under resting conditions in 13 young (Y = 24 ± 1 years), 17 older untrained (OU = 66 ± 1 years), and 16 older endurance exercise trained adults (OT = 66 ± 2 years). Mean shear rate (s−1) was defined as 4·Vm/D, where Vm is mean blood velocity (cm · s−1) and D is arterial diameter (cm). For calculations of antegrade and retrograde shear rate, antegrade and retrograde mean blood velocities were used, respectively. Oscillatory shear index is an indicator of the magnitude of oscillation between antegrade and retrograde shear. Vascular resistance in the forearm and leg were also calculated (mean arterial pressure/blood flow) using each respective limb blood flow and mean arterial pressure derived from beat‐to‐beat finger plethysmography measurements. Brachial artery retrograde (−9.1 ± 1.7 vs. −12.6 ± 2.3 s−1; P = 0.35) and oscillatory (0.14 ± 0.02 vs. 0.14 ± 0.02 arbitrary units; P = 0.99) shear were similar between the OT and OU groups, whereas brachial retrograde and oscillatory shear were greater in OU compared to Y adults (−5.0 ± 0.9 s−1, 0.08 ± 0.01 arbitrary units, both P &lt; 0.05; respectively). There was no difference between the Y and OT brachial artery retrograde (P = 0.29) and oscillatory (P = 0.07) shear. Common femoral artery retrograde (−6.3 ± 0.7 s−1) and oscillatory (0.21 ± 0.02 arbitrary units) shear was reduced in OT compared to the OU group (−10.4 ± 1.0 s−1 and 0.30 ± 0.02 arbitrary units, both P &lt; 0.05; respectively), yet similar to Y adults (−7.1 ± 1.0 s−1 and 0.19 ± 0.02 arbitrary units, P = 0.81 and 0.87; respectively). Vascular resistance did not differ between groups in the arm (P = 0.56) or the leg (P = 0.32). However, vascular resistance was inversely related to retrograde shear in the brachial and common femoral artery (r = −0.33 and −0.37, both P &lt; 0.05; respectively) and positively related to oscillatory shear in the brachial and common femoral artery (r = 0.46 and 0.54, both P &lt; 0.05; respectively) when all subjects were pooled together. Our results suggest that chronic endurance exercise training in older adults ameliorates retrograde and oscillatory shear rate patterns, particularly in the common femoral artery.Support or Funding InformationResearch was supported by NIH HL‐105467 (DPC)

Minimally invasive highly precise monitoring of respiratory rhythm in the mouse using an epithelial temperature probe

BackgroundRespiration is one of the essential rhythms of life. The precise measurement of respiratory behavior is of great importance in studies addressing olfactory sensory processing or the coordination of orofacial movements with respiration. An ideal method of measurement should reliably capture the distinct phases of respiration without interfering with behavior. New methodThis new method involves chronic implantation of a thermistor probe in a previously undescribed hollow space located above the anterior portion of the nasal cavity without penetrating any soft epithelial tissues. ResultsWe demonstrate the reliability and precision of the method in head-fixed and freely moving mice by directly comparing recorded signals with simultaneous measurements of chest movements and plethysmographic measurements of respiration. Comparison with existing methodsCurrent methods have drawbacks in that they are either inaccurate or require invasive placement of temperature or pressure sensors into the sensitive nasal cavity, where they interfere with airflow and cause irritation and damage to the nasal epithelium. Furthermore, surgical placement within the posterior nasal cavity adjacent to the nasal epithelium requires extensive recovery time, which is not necessary with the described method. ConclusionsHere, we describe a new method for recording the rhythm of respiration in awake mice with high precision, without damaging or irritating the nasal epithelium. This method will be effective for measurement of respiration during experiments requiring free movement, as well as those involving imaging or electrophysiology.

Ventilation Heterogeneity in Never-smokers and COPD:: Comparison of Pulmonary Functional Magnetic Resonance Imaging with the Poorly Communicating Fraction Derived From Plethysmography

Pulmonary functional magnetic resonance imaging provides a way to quantify ventilation and its heterogeneity-a hallmark finding in chronic obstructive pulmonary disease (COPD). Unfortunately, the etiology and physiological meaning of ventilation defects and their relationship to pulmonary function and symptoms in COPD are not well understood. Another biomarker of ventilation heterogeneity is provided by the "poorly communicating fraction" (PCF), and is calculated as the ratio of total lung capacity to alveolar volume made using whole-body plethysmography. Our objective was to compare ventilation heterogeneity using hyperpolarized (3)He magnetic resonance imaging (MRI) and PCF measurements in elderly never-smokers and in ex-smokers with COPD. One hundred forty-six participants (71 ± 8 years, range = 48-87 years) provided written informed consent including 45 elderly never-smokers (71 ± 6 years, range = 61-84 years) and 101 ex-smokers with COPD (71 ± 8 years, range = 48-87 years). During a single 2-hour visit, spirometry, plethysmography, and hyperpolarized (3)He MRI were acquired. The MRI-derived ventilation defect percent (VDP) and plethysmography measurements were acquired and PCF values were calculated. Linear regression, Pearson correlations, and Bland-Altman analysis were used to evaluate the relationships for PCF and MRI VDP. PCF (P < 0.001) and VDP (P < 0.001) were significantly increased with increasing COPD severity. There was a significant relationship for VDP and PCF (r = 0.68, P < 0.001) in all subjects and COPD subjects alone (r = 0.61, P < 0.001). Bland-Altman analysis showed that PCF and VDP were significantly different (mean bias = 9.7, upper limit = 32, lower limit = -13, P < 0.001), and in severe-grade COPD, PCF overestimates of VDP were significantly greater. In elderly never-smokers and in ex-smokers with COPD, PCF and VDP are moderately correlated estimates of COPD ventilation heterogeneity that may be reflecting similar pathophysiology.

Comparison of Body Composition Assessed by Air Displacement Plethysmography and Skin-Fold Technique in Post Menopausal Women

Assessment of body composition is vital in maintaining good health and managing various health problems. The proportion of the components of the body varies with various stages of life. Menopause and associated hormonal changes leads to alterations in body composition. Therefore accurate assessment of body composition in post menopausal women will help in prevention and management of various non-communicable diseases. Many methods are available to assess body composition; however the choice of the methods depends on factors like accuracy, accessibility and cost. The comparison of different methods helps in understanding the relative accuracy of the methods. The present study was conducted with an objective to compare the body composition estimated by Air Displacement Plethysmography (ADP) and skin-fold measurement (SKF) in post menopausal women. Twenty one apparently healthy post menopausal women aged 45-60 years were included in the study. Body composition was assessed using ADP (BodPod, LMI, USA) and SKF (Holtain Calipers, UK) methods to obtain per cent body fat and fat free mass (FFM) and agreement between the methods was assessed using paired t-test and Bland-Altman plots. It was found that there was no significant difference between the body fat per cent (p = 0.83), fat mass (p = 0.78) and fat free mass (p = 0.78) estimated by ADP and SKF. The biases for body fat per cent, fat mass and fat free mass were -0.2 %, -0.1 kg and 0.1 kg respectively. It can be concluded that there is a reasonable agreement between the methods in postmenopausal women.

Cardiac output and vasodilation in the vasovagal response: An analysis of the classic papers

The simple faint is secondary to hypotension and bradycardia resulting in transient loss of consciousness. According to Ohm's law applied to the circulation, BP = SVR × CO, hypotension can result from a decrease in systemic vascular resistance (SVR), cardiac output (CO), or both. It is important to understand that when blood pressure (BP) is falling, SVR and CO do not change reciprocally as they do in the steady state. In 1932, Lewis, assuming that decreased SVR alone accounted for hypotension, defined "the vasovagal response" along pathophysiologic lines to denote the association of vasodilation with vagal-induced bradycardia in simple faint. Studies performed by Barcroft and Sharpey-Schafer between 1940 and 1950 used volume-based plethysmography to demonstrate major forearm vasodilation during extreme hypotension and concluded that the main mechanism for hypotension was vasodilation. Plethysmographic measurements were intermittent and not frequent enough to capture rapid changes in blood flow during progressive hypotension. However, later investigations by Weissler, Murray, and Stevens performed between 1950 and 1970 used invasive beat-to-beat BP measurements and more frequent measurements of CO using the Fick principle. They demonstrated that CO significantly fell before syncope, and little vasodilation occurred until very late in the vasovagal reaction Thus, since the 1970s, decreasing cardiac output rather than vasodilation has been regarded as the principal mechanism for the hypotension of vasovagal syncope.

About the discovery of an explicit model to monitor blood pressure in a non-invasive way

Purpose: The objective of the study was to identify an explicit model to indirectly monitor blood pressure by using the electrocardiography and heart rate variability parameters, and the plethysmography. Those latter signals can be monitored through wearable non-invasive sensors, namely an electrocardiography sensor and a finger pulse oximeter sensor. The developed model was included in a real-time mobile monitoring system to realize a wearable continuous non-invasive arterial pressure monitor. Context: Continuous non-invasive arterial pressure methods can be used to continuously measure arterial blood pressure in real time and without any need for patient's body cannulation. Currently there is a high request for accurate and easy-to-use continuous non-invasive arterial pressure systems. Consequently, an increasing focus on these devices exists. Several non-invasive approaches to blood pressure have been attempted, some of which are described in [1]. Methods: The explicit model was developed under the form of a function by combining heart rate variability parameters and plethysmography measurements. We decided to avail ourselves of a Genetic Programming technique for this regression problem because it can automatically find an explicit model for the relationship between the independent variables and a dependent one, in this case one between the systolic and the diastolic blood pressure values. Therefore, once hypothesized the existence of a nonlinear relationship between heart activity, and thus electrocardiography and heart rate variability parameters, plethysmography and blood pressure values, and chosen a fitness function, we found, from among the huge number of possible models, the one that best describes the fundamental features of this relationship.

Plethysmography measurements of respiratory function in conscious unrestrained mice.

Whole body plethysmography (WBP) is used to quantify pulmonary function in conscious, unrestrained mice. We determined currently whether time of day and environmental lighting influence day-to-day reproducibility of pulmonary function, and quantifed the necessary habituation time in the WBP chamber. Two-month-old male C57BL6 and mdx mice (n = 8/group, reverse light cycle), were examined on consecutive days using a calibrated WBP chamber and manufacturer software was used to calculate respiratory measures. Respiratory data stabilized between 5-10 min for all variables. Mice exhibited time of day respiratory differences, performing more forceful and less frequent breaths midday (11:45 a.m. and 3:00 p.m.) compared to 7:30 a.m. WBP performed in darkened conditions elicited more forceful breathing than lit conditions. Day-to-day reproducibility during controlled conditions ranged from r(2) = 0.58 to 0.62 for the functional measures. Findings indicate reproducible respiratory data are obtainable following a 15-min chamber habituation and standardization of time of day and room lighting.

Respiratory dysfunction in multiple sclerosis: A preliminary study of respiratory dysfunction in patients with motor disability

Respiratory dysfunction is one of the main causes of morbidity during the course of multiple sclerosis. We distinguish four main causes for respiratory dysfunction: respiratory muscles weakness, deglutition disorders, sleep disordered breathing, and control of breathing abnormalities [1] . The main purpose of this study was to describe the respiratory function of MS patients with motor disability. We conducted a prospective study in MS patients with a walking disability. The respiratory dysfunction was assessed with pulmonary function tests, using spirometric and plethysmographic measures. The motor respiratory dysfunction was assessed using the vital capacity (VC), in the sitting and upright positions. Maximum inspiratory and expiratory pressures were also measured. We also reviewed the history of associated deglutition and sleep disorders. Over a 2-year period, 81 patients were evaluated. The median EDSS was 8 (IQ 7–8.5), the mean duration of disease was 20 years ± 11.4 and mean time since loss of walking ability 6.9 years ± 5.3. The average vital capacity was 2.41 L ± 1.08, i.e. 70,7 ± 0.3% of theoretical value. Fifty-one patients (63%) had a significative decrease of VC (<80%), being considered as severe (VC < 50%) in 23 cases (28%). In patients with severe MS, respiratory dysfunction is frequent. Its diagnosis and a better knowledge of its complications could help physicians to provide more specific care.

Poor standardisation of plethysmographic specific airways resistance measurement despite widespread use

s R aw is widely used but results should be interpreted with caution until its recording is better standardised http://ow.ly/QvJRJ

RMR Estimation Model Accuracy Using Air Displacement Plethysmography–Derived Body Composition Measures in Young Adults

Objective: Predictive equations derived from regression techniques based on large samples are extensively utilized in estimating resting metabolic rate (RMR). Body composition assessments utilize model equations to estimate RMR. However, the agreement of these predictive models with indirect calorimetery (IC) has come into question. Our aim is to investigate the agreement of RMR estimation models using air displacement plethysmography (ADP) measures against a gas exchange IC system (RMR-C).Methods: Sixty-six participants (25 men, 41 women) completed the study. RMR measurements were obtained from IC and ADP within 10 minutes of one another. IC RMR estimates were tested against 9 other validated models using ADP measures via analysis of variance (ANOVA) techniques with multiple comparisons testing and Bland-Altman analysis.Results: Based on the ANOVA, the Nelson (1992) model underpredicted RMR compared to IC (p < 0.001). The Doré et al. (1982) model was the best predictor of RMR compared to the IC measures (p = 0.907).Discussion: The current RMR estimation model using ADP measures underpredicts total caloric needs. The Doré et al. (1982) model more accurately predicted RMR in the entire sample.

Non-invasive blood haemoglobin and plethysmographic variability index during brachial plexus block

Plethysmographic measurement of haemoglobin concentration ([Formula: see text]), pleth variability index (PVI), and perfusion index (PI) with the Radical-7 apparatus is growing in popularity. Previous studies have indicated that [Formula: see text] has poor precision, particularly when PI is low. We wanted to study the effects of a sympathetic block on these measurements. Twenty patients underwent hand surgery under brachial plexus block with one Radical-7 applied to each arm. Measurements were taken up to 20 min after the block had been initiated. Venous blood samples were also drawn from the non-blocked arm. During the last 10 min of the study, [Formula: see text] had increased by 8.6%. The PVI decreased by 54%, and PI increased by 188% in the blocked arm (median values). All these changes were statistically significant. In the non-blocked arm, these parameters did not change significantly. Brachial plexus block significantly altered [Formula: see text], PVI, and PI, which indicates that regional nervous control of the arm greatly affects plethysmographic measurements obtained by the Radical-7. After the brachial plexus block, [Formula: see text] increased and PVI decreased.

Cardio-ankle Vascular Index as an Alternative Measure for Arterial Health

PURPOSE: The American Heart Association places measurements of arterial function as a priority for diagnosing cardiovascular health. The Cardio-Ankle Vascular Index (CAVi) is a static measurement, independent of blood pressure, which is an indicator of arterial stiffness; whereas strain-gauge plethysmography measures dynamic arterial function. CAVi may provide an alternative to functional measurements, like strain-gauge plethysmography when testing arterial health. Furthermore, sex or fitness may be important to these measurements of arterial health. The purpose of this study was to compare the relationship between CAVi and strain-gauge plethysmography, while addressing fitness and gender. METHODS: CAVi was measured in 23 participants (8 female, 23 ± 3 years, BMI 23 ± 3) (VaSera,Fukuda Denshi, Japan) and dynamic arterial function was measured using strain-gauge plethysmography . Plethysmographic variables include: late phase (LP) forearm blood flow (FBF), area under the curve (AUC) FBF, LP AUC FBF, LP forearm vascular conductance (FVC). VO2peak was assessed on a cycle ergometer using an incremental test. RESULTS: Cavi was correlated to LPFBF, AUC peak FBF, LP AUC FBF, and LP FVC (P<0.05). (See Table) Males maintained significant correlations for the above variables (P<0.05), but females did not. VO2peak was not correlated with CAVi in males or females. CONCLUSIONS: CAVi, a relatively easy measurement in a clinical setting, could potentially act as an alternate for the more time consuming measurement of plethysmography (which is not a clinical measure); but CAVi may only be useful measurement of arterial function in males.

Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ETA/ETB) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20mgkg−1day−1, 10days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ETA (increases) and ETB (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5mgkg−1day−1), celecoxib (10mgkg−1day−1) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ETA/ETB receptor expressions. Selective blockade of ETA receptors by atrasentan (5mgkg−1day−1) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ETB receptor blocker, 0.1mgkg−1day−1) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ETA downregulation and ETB upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen.

A role of respiratory functional investigation for detection of lung diffusion disorders in patients with pulmonary sarcoidosis admitted to in a multidisciplinary military hospital

The aim of this study was to analyze lung function parameters and lung diffusing capacity in servicemen with pulmonary sarcoidosis. Methods. The study involved 45 patients with newly diagnosed active pulmonary sarcoidosis which was determined by biopsy. The mean age of the patients was 39.4 ± 10.9 years. Spirometry, body plethysmography, and single-breath measurement of lung diffusing capacity for carbon monoxide (DL CO ) were performed in all the patients. Results. Normal forced spirometry parameters were found in 66.7% of the patients. Meanwhile, 13.3% of the patients had restrictive ventilation disorders, 23.3% had reduced RV without any changes and 33.3% had reduced DL CO . Conclusions. The results demonstrated a little diagnostic value of the standard spirometry in patients with pulmonary sarcoidosis. In these patients, the spirometry should be added by measurement of lung volume and lung diffusing capacity.

Stimulation of Nitric Oxide Synthase Activity By Plasma Apolipoproteins: a Biomarker of Endothelial Function in Adults with Sickle Cell Disease

Nitric oxide (NO) plays a critical role in maintaining basal vascular tone and regulating blood flow. Many factors, including shear stress and endogenous ligands such as vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF1), stimulate the activity of endothelial nitric oxide synthase (eNOS). We have developed a bioassay that measures stimulation of NOS activity by soluble factors in unfractionated human plasma in cultured human endothelial cells using a sensitive NOS activity assay with radiolabeled substrate.The addition of 1% human plasma to the culture medium stimulates NOS activity 1.5-fold over background, with a linear response up to 10% plasma, which activates NOS 5.5-fold. We have concluded from several lines of evidence that this NOS-inducing activity in human plasma comes from high-density lipoprotein (HDL): The activity is heat-labile and sensitive to reducing agents; it is precipitable by ammonium sulfate and elutes as a broad peak on molecular exclusion and anion exchange columns; by immunoblot, the active fractions have large amounts of apolipoproteins apoA-I, apoE and paroxonase-1. We find that plasma from an apoA-I null mouse shows less stimulation of NOS activity in our bioassay than plasma from a wild type mouse and apoA-I transgenic mouse (p=0.06, Brown-Forsythe test; p=0.04, post-test for linear trend; see figure). Purified HDL fractions stimulate NOS activity four-fold, equivalent to unfractionated plasma, but further subfractionation of HDL components extinguishes its ability to activate NOS.Remarkably, higher than median NOS-stimulating activity in our bioassay was associated with endothelial-dependent blood flow, detected by venous occlusion strain gauge plethysmography measurement of forearm blood flow induced by graded infusions of acetylcholine into the brachial artery in adults with sickle cell anemia (p=0.0013, two-way ANOVA, see figure). The NOS-stimulating activity in patient plasma also correlated with the plasma apoA-I level (Spearman r=0.64, p=0.0012).In summary, our results suggest that circulating functional apoA-I and possibly other apolipoproteins, regulate NO production and endothelial function in adults with sickle cell disease, which is consistent with previous lines of evidence published by other investigators in subjects without sickle cell disease. Most strikingly, our plasma NOS stimulation assay appears to provide a useful research biomarker for endothelial function, applicable to frozen archived plasma biospecimens. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.