Changes in electrodermal activity following sympathicotomy in hyperhidrosis patients.

Objectives: The aim of this study was to assess the potential of electrodermal activity (EDA) as a diagnostic tool for preoperative evaluation in hyperhidrosis patients. EDA levels and patterns in different skin areas were investigated before and after endoscopic thoracic sympathicotomy (ETS) and was compared to healthy subjects. Methods: Thirty-seven patients underwent two days of measurements before and after the operation. Twenty-five (67.5%) of the patients also had a third measurement after six months. Non-invasive EDA measurements, involving skin conductance, were sampled from five different skin areas while patients were at rest in supine and sitting positions or when subjected to stimuli such as deep inspirations, mental challenge, and exposure to a sudden loud sound. Results: Prior to the operation, hyperhidrosis patients showed higher spontaneous palm EDA variations at rest and stronger responses to stimuli compared to healthy subjects. Patients with facial blushing/hyperhidrosis or combined facial/palmar hyperhidrosis showed minimal spontaneous activity or responses, particularly during mental challenge and sound stimulus. Notably, palm EDA response was abolished shortly following sympathicotomy, although a minor response was observed after six months. Minimal EDA responses were also observed in the back and abdomen postoperatively. Conclusion: Hyperhidrosis patients showed stronger EDA response to stimuli compared to healthy subjects. Sympathicotomy resulted in the complete elimination of palm EDA responses, gradually returning to a limited extent after six months. These findings suggest that EDA recordings could be utilized in preoperative assessment of hyperhidrosis patients.

Pathologic Blood Samples Tolerate Exposure to Vibration and High Turbulence in Simulated Drone Flights, but Plasma Samples Should be Centrifuged After Flight.

OBJECTIVE: Most of the previous studies of drone transport of blood samples examined normal blood samples transported under tranquil air conditions. We studied the effects of 1- and 2-hour drone flights using random vibration and turbulence simulation (10-30 g-force) on blood samples from 16 healthy volunteers and 74 patients with varying diseased. METHODS: Thirty-two of the most common analytes were tested. For biochemical analytes, we used plasma collected in lithium heparin tubes with and without separator gel. Gel samples were analyzed for the effect of separation by centrifugation before or after turbulence. Turbulence was simulated in an LDS V8900 high-force shaker using random vibration (range, 5-200 Hz), with samples randomly allocated to 1- or 2-hour flights with 25 or 50 episodes of turbulence from 10 to 30 G. RESULTS: For all hematologic and most biochemical analytes, test results before and after turbulence exposure were similar (bias < 12%, intercepts < 10%). However, aspartate aminotransferase, folate, lactate dehydrogenase and lipid index increased significantly in samples separated by gel and centrifugation prior to vibration and turbulence test. These changes increased form 10 G to 30 G, but were not observed when the samples were separated after vibration and turbulence. CONCLUSIONS: Whole blood showed little vulnerability to turbulence, whereas plasma samples separated from blood cells by gel may be significantly influenced by turbulence when separated by spinning before the exposure. Centrifugation of plasma samples collected in tubes with separator gel should be avoided before drone flights that could be subject to turbulence.

Rapid, Large, and Synchronous Sweat and Cardiovascular Responses Upon Minor Stimuli in Healthy Subjects. Dynamics and Reproducibility.

Purpose: The aim of the study was to investigate steady state levels, dynamics and reproducibility of cardiovascular variables and electrodermal activity in different skin areas in response to minor physiological and mental stimuli in healthy subjects in the thermoneutral zone, carried out in high time resolution. Methods: Thirteen healthy subjects underwent experiments on two separate days. Non-invasive electrodermal activity in five different skin areas was measured continuously using a skin conductance method, including resting supine and sitting positions, performing deep inspirations, a mental challenge and being exposed to a sudden loud sound. Blood pressure, heart rate, radial artery blood flow, and skin perfusion were measured simultaneously. Results: Electrodermal activity in the right and left palms was almost identical, with rapid and large increases within a few seconds in response to stimuli, whereas no such significant changes were seen in the face, back, and abdomen. Radial artery blood flow and palmar skin perfusion changed synchronously with electrodermal activity for each stimulus, and were correlated to changes in blood pressure and heart rate. The response patterns in each subject were very similar on the two experimental days. There was very low spontaneous electrodermal activity in the supine position, contrary to the resting sitting position. Conclusion: The electrodermal activity increased rapidly and synchronously in both palms within a few seconds as a response to minor physiological and mental stimuli, synchronous with fluctuations in radial artery blood flow, palmar skin perfusion, and cardiovascular variables. The responses are reproducible from day to day, making them a stable and constant stimuli to be used for studies in patients with hyperhidrosis.

Automated alarm to detect antigen excess in serum free immunoglobulin light chain kappa and lambda assays.

BACKGROUND: Antigen excess causing a falsely low concentration result may occur when measuring serum free immunoglobulin light chains (SFLC). Automated antigen excess detection methods are available only with some analyzers. We have now developed and verified such a method. METHODS: Residuals of sera with known SFLC-κ and -λ concentrations were analyzed using Binding Site reagents and methods adapted to the Roche Cobas® c.501 analyzer. RESULTS: We analyzed 117 sera for SFLC-κ and -λ and examined how the absorbance increased with time during the 7 minutes of reaction (absorbance reading points 12-70). From this an antigen excess alarm factor (ratio of absorbance increases between reading points 68-60 and 20-12, multiplied by 100) was defined. Upon our request, Roche added to our two SFLC assays a program which calculated this antigen excess alarm factor and triggered an alarm when the factor was below a defined value. We verified this antigen excess alarm function by analyzing serum from 325 persons of whom 143 were multiple myeloma patients. All samples with a known concentration above 30 mg/L triggered either an antigen excess alarm, an 'above test' alarm or both. Also, all samples above 200 mg/L (SFLC-λ) and 300 mg/L (SFLC-κ) triggered the antigen excess alarm and all but one triggered the above test alarm. CONCLUSIONS: The antigen excess alarm function presented here detected all known antigen excess samples at no increased time of analysis, a reduced workload and reduced reagent cost.

Changes in blood pressure during healthy pregnancy: a longitudinal cohort study.

OBJECTIVE: To study longitudinally changes in blood pressure (BP) and heart rate (HR) during healthy pregnancies and to evaluate the influence of parity, pregestational overweight, and excessive weight gain. METHODS: A prospective longitudinal cohort study of 57 healthy white women with singleton pregnancies. BP and HR were measured repeatedly at gestational age 14-16 weeks, 22-24 weeks, 30-32 weeks, 36 weeks, and 6 months postpartum using both an oscillometric measurement device (Dinamap) and finger arterial pressure (Finometer PRO). RESULTS: SBP, DBP, and mean arterial pressure (MAP) reached a statistically significant trough at gestational age 22-24 weeks using both measurement devices. When compared with the nonpregnant measurement, SBP at gestational age 22-24 weeks was 6.2 mmHg [95% confidence interval (95% CI) 1.3-11.2] lower measured by Finometer and 7.2 mmHg (95% CI 4.2-10.1) lower measured by Dinamap. DBP and MAP were 8.9 mmHg (95% CI 4.6-13.2) and 9.8 mmHg (95% CI 5.3-14.2) lower measured by Finometer. Measured by Dinamap, DBP and MAP were 4.5 mmHg (95% CI 1.7-7.3) and 5.4 mmHg (95% CI 2.8-7.9) lower at gestational age 22-24 weeks when compared with the nonpregnant state. SBP was significantly higher in women with pregestational BMI at least 25 kg/m with both measurement devices (both P < 0.05). There were no differences in SBP, DBP, or MAP depending on parity or excessive weight gain. CONCLUSION: BP measured repeatedly by two different noninvasive devices during pregnancy and postpartum showed a statistically significant drop in mid-pregnancy, followed by a progressive increase until term.

Low-frequency fluctuations in heart rate, cardiac output and mean arterial pressure in humans: what are the physiological relationships?

OBJECTIVE: Cardiovascular variability is a complex physiological phenomenon associated with the outcome of cardiovascular diseases. Blood pressure oscillations may cause cardiovascular complications, which, however, are also claimed to have antihypertensive effects. The physiological understanding is limited. This study evaluates whether oscillations in heart rate (HR) and cardiac output (CO) buffer fluctuations at approximately 0.1 Hz in arterial blood pressure (Mayer waves). METHOD: We recorded mean arterial pressure (MAP), left cardiac stroke volume (SV), and HR in 10 healthy humans during autonomic blockade in supine and tilted (30 degrees) position. Variability in the cardiovascular variables at 0.04-0.15 Hz and phase angles (time lags) between the variables were calculated by spectral analysis. RESULTS: Fluctuations in cardiovascular variables at 0.1 Hz decreased after removal of HR variability (HRV) by propranolol and atropine in the supine position. Tilting from supine did not change fluctuations in MAP or total peripheral resistance (TPR), whereas variations in CO decreased. Variations in CO remained decreased in tilt after atropine compared to supine control, whereas variations in MAP and in TPR were unchanged. HRV were in phase with oscillations in CO. Variations in CO were in inverse phase with variations in TPR. CONCLUSION: TPR oscillations produce fluctuations in MAP at 0.1 Hz. HRV produces CO variations, but CO variations do not efficiently buffer MAP variations during supine rest and mild ortostasis. Both feedback and feedforward mechanisms are responsible for the interaction between HR and MAP.

Role of sympathetic responses on the hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fractional, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT), termed the "push-pull effect." The aim of the present study was to test the hypothesis that sympathetic responses contribute to the push-pull effect. Young, healthy subjects (n = 7 males and 3 females) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced design, and 1 min was allowed for recovery between tilts. This protocol was repeated during clonidine administration (2.5 microg/kg bolus over 30 min and then continuously at 0.36 microg x kg(-1) x h(-1)). Clonidine blunted the vasomotor responses to tilting, and this led to exaggerated changes in arterial pressure. Clonidine exerted little specific influence on the push-pull effect. Thus sympathetic responses appear neither to contribute to, nor protect against, the push-pull effect for the rate and duration of tilting imposed in the present study.

Retrograde arterial leg blood flow during tilt-back from a head-up posture: importance of capacitive flows when arterial pressure changes.

The windkessel function of the arterial system converts the intermittent action of the heart into more continuous microcirculatory blood flow during diastole via the return of elastic energy stored in the walls of the arteries during systole. Might the same phenomenon occur regionally within the arterial system during tilting owing to regional differences in local arterial pressure imposed by gravity? We sought to test the hypothesis that during tilt-back from a head-up posture, the return of stored elastic energy in leg arteries would work to slow, or perhaps transiently reverse, the flow of blood in the femoral artery. Femoral artery blood flow and arterial pressure were recorded during tilt back from a 30 degrees head-up posture to supine (approximately 0.5 G) in young, healthy subjects (n = 7 males and 3 females) before and during clonidine infusion. During control (no drug) conditions femoral artery blood flow ceased for an entire heart beat during tilt-back. During clonidine infusion femoral artery blood flow reversed for at least one entire heart beat during tilt-back, i.e., blood flow in the retrograde direction in the femoral artery from the leg into the abdomen. Thus substantial capacitive effects of tilting on leg blood flow occur in humans during mild changes in posture.

Effect of the leg muscle pump on the rise in muscle perfusion during muscle work in humans.

The transient and steady-state effects of the calf muscle pump on the rise in muscle perfusion during rhythmic plantarflexions were investigated in 20 volunteers. Because a large hydrostatic column would increase the effect of a muscle pump, exercise in the supine and head-up tilted positions was compared. Within approximately 15 s of the start of muscle work, femoral artery flow (ultrasound Doppler) rose 0.37 L/min above rest in the supine and 0.5 L/min above rest in the tilted position. The latter is a significantly larger rise (P < 0.05). After 80 s of muscle work, femoral flow was stable at 0.38 and 0.39 L/min above rest in the supine and tilted positions, respectively. We conclude that the muscle pump contributes to muscle perfusion during the initial phase of muscle work, but that metabolic vasodilation is a more important determinant of muscle perfusion during steady-state muscle work.

Hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fraction, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT). The aims of the present study were to characterize the hemodynamic consequences of brief HDT on subsequent HUT and to test the hypothesis that an elevation in leg vascular conductance induced by -G(z) stress contributes to the exaggerated fall in ELAP. Young healthy subjects (n = 3 men and 4 women) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced designed to minimize possible time effects of repeated exposure to gravitational stress. One minute was allowed for recovery between tilts. Brief exposure to HDT elicited an exaggerated fall in ELAP during the first seconds of the subsequent HUT (-17.9 +/- 1.4 mmHg) compared with HUT alone (-12.4 +/- 1.2 mmHg, P <0.05) despite a greater rise in stroke volume (Doppler ultrasound) and cardiac output over this brief time period in the HDT-HUT trials compared with the HUT trials (thereafter stroke volume fell under both conditions). The greater fall in ELAP was associated with an exaggerated increase in leg blood flow (femoral artery Doppler ultrasound) and was therefore largely (70%) attributable to an exaggerated rise in estimated leg vascular conductance, confirming our hypotheses. Thus brief exposure to -G(z) stress leads to an exaggerated fall in ELAP during subsequent HUT, owing to an exaggerated increase in estimated leg vascular conductance.

Regulation of arterial blood pressure in humans during isometric muscle contraction and lower body negative pressure.

Previous studies have shown that the blood pressure response to isometric handgrip remains unchanged during reductions in preload induced by lower body negative pressure (LBNP). The purpose of the present study was to assess the beat-by-beat haemodynamic mechanisms allowing for precise control of mean arterial pressure (MAP). We have followed the cardiovascular variables involved in the regulation of MAP during isometric handgrip with and without additional application of LBNP during defined periods of the ongoing contraction. Sixteen subjects participated. Mean arterial blood pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), blood flow velocity in the brachial artery, acral skin blood flow, as well as total (TPR) and local (LPR) peripheral resistance were continuously recorded/calculated before, during and after 2 min of handgrip both with and without concomitant LBNP. The main finding was that MAP increased at the same rate and to the same absolute level whether or not LBNP was applied. A uniform increase in MAP was observed even though the cardiovascular variables evolved differently in the periods with and without LBNP. At the onset of LBNP at -20 mmHg, there was a transient drop in MAP and a transient increase in HR, but within seconds, MAP was regulated back to the slope caused by the isometric handgrip proper. CO and SV, which were declining gradually, showed an additional marked but gradual reduction upon LBNP application. At the same time, both LPR and TPR increased markedly and continuously. In summary, the increase in MAP during isometric handgrip remained essentially unchanged by LBNP-induced alterations in preload. The increase in MAP was caused by a marked increase in peripheral resistance. This supports the concept of a central set point, continuously regulated upwards as long as the isometric handgrip persists. Furthermore, it reveals a considerable flexibility in the cardiovascular control mechanisms used to achieve the desired arterial pressure.

Design of a chamber for lower body negative pressure with controlled onset rate.

We have designed a lower body negative pressure (LBNP) chamber and control system that makes it possible to apply LBNP either very rapidly (< 300 ms), or more gradually, according to predefined protocols. The capability of the new, high-performance agile aircraft to reach a high-G onset rate makes it highly desirable to be able to study immediate, rapid, and transient cardiovascular responses to simulated gravitational stress. Our new LBNP chamber has been used to study the main cardiovascular variables during onset and release of mild LBNP (-20 mmHg). We have revealed large transient physiological responses during the onset and release of mild LBNP. This new finding was largely made possible by precise control of the onset and release of LBNP during the experiments. The purpose of this paper is therefore to describe some of the technical solutions which made rapid and controlled changes in LBNP possible, focusing on the importance of precise control of the LBNP chamber.

Beat-to-beat noninvasive stroke volume from arterial pressure and Doppler ultrasound.

The proper understanding of the cardiovascular mechanisms involved in complaints of short-lasting dizziness and the evaluation of unexplained recurrent syncope requires continuous monitoring of cardiac stroke volume (SV) in addition to blood pressure and heart rate. The primary aim of the present study was to evaluate a pulse wave analysis method that calculates beat-to-beat flow from non-invasive arterial pressure by simulating a non-linear, time-varying model of human aortic input impedance (Modelflow; MF), by comparing MF stroke volume (SV(MF)) to Doppler ultrasound (US) flow velocity SV (SV(US)). A second purpose was to compare the two methods under two different conditions: the supine and head-up tilt (30 degrees ) position. SV(US) and SV(MF) with non-invasive arterial pressure (Finapres) as input to the aortic model were measured beat-to-beat during spontaneous supine breathing and in the passive 30 degrees head-up tilt (HUT30) position in six normotensive healthy humans [three females, mean age 24 (21-26) years]. There were variations in supine SV track between the two methods with zero difference and a SD of the beat-to-beat difference (MF-US) of 4.2%. HUT30 induced a systematic difference of 10.5% and an increase in SD to 6.9%, which was reproducible. Beat-to-beat changes in SV in the supine resting condition were equally well assessed by both methods. Systematic differences appear during HUT30 and show opposite signs. The difference between the two methods upon a change in body position may be attributed to limitations in each method.

Beat-to-beat measurement of the finger arterial pressure pulse shape index at rest and during exercise.

Arterial pressure waveform can be characterized by the pulse shape index kpulse determined as kpulse = (Pmean - Pdiast) / (Psyst - Pdiast). For brachial artery, the shape index value of 0.33 is usually applied to approximate Pmean from the measured Psyst and Pdiast. Our purpose was to test whether this value can validly be applied to finger vascular beds under different experimental conditions. By using Finapres, we non-invasively estimated the beat-to-beat values of kpulse in the fingers of young healthy persons in supine position at rest and during a 4-min moderate exercise (rhythmical exercise with the quadricep muscles in combination with handgrip compression). To detect intensive peripheral vasoconstrictions, a laser-Doppler probe was attached to the thumb pulp of the same hand. Periods of 30 s without intensive vasoconstriction for rest, different stages of exercise and recovery were involved in the analysis in every subject. The results demonstrated that the group-averaged value of kpulse (median with a 95% confidence interval) in the fingers of 11 healthy volunteers aged from 20 to 24, equalled 0.33 (0.31- 0.34), 0.31 (0.28-0.34), 0.35 (0.33-0.39) and 0.38 (0.34-0.43) for rest, first and second stages of exercise and recovery, respectively. We conclude that in the fingers of young healthy persons in supine position formula Pmean = Pdiast + 1/3 (Psyst - Pdiast) gives an adequate approximation for rest and low intensity exercise (first stage), and slightly underestimates the actual finger mean blood pressure during moderate exercise (second stage) and recovery.

Noninvasive identification of the total peripheral resistance baroreflex.

We propose two identification algorithms for quantitating the total peripheral resistance (TPR) baroreflex, an important contributor to short-term arterial blood pressure (ABP) regulation. Each algorithm analyzes beat-to-beat fluctuations in ABP and cardiac output, which may both be obtained noninvasively in humans. For a theoretical evaluation, we applied both algorithms to a realistic cardiovascular model. The results contrasted with only one of the algorithms proving to be reliable. This algorithm was able to track changes in the static gains of both the arterial and cardiopulmonary TPR baroreflex. We then applied both algorithms to a preliminary set of human data and obtained contrasting results much like those obtained from the cardiovascular model, thereby making the theoretical evaluation results more meaningful. This study suggests that, with experimental testing, the reliable identification algorithm may provide a powerful, noninvasive means for quantitating the TPR baroreflex. This study also provides an example of the role that models can play in the development and initial evaluation of algorithms aimed at quantitating important physiological mechanisms.

Model simulations of cardiovascular changes at the onset of moderate exercise in humans.

We have tested whether the cardiovascular changes at the onset of exercise could be simulated only by an increase in the baroreflex set point and locally induced vasodilatation in the exercising muscles. The mathematical model consists of a heart, a linear elastic arterial reservoir and two parallel resistive vascular beds. The arterial baroreflex loop is modelled by three separate time domain processing objects, each with its own gain, time constant and delay. These are intended to simulate the action of a sympathetic signal to the peripheral vascular bed, a parasympathetic signal to the heart and a sympathetic signal to the heart. We used this model with previously published experimental data to estimate the unknown parameters in the reflex control loop. In all 10 subjects and in the global averaged response, the short-term cardiovascular responses were adequately simulated by using individual sets of parameters in the model. An increase in the baroreflex set point and locally induced vasodilatation in the exercising muscles can explain almost all of the cardiovascular changes in the recorded variables (mean arterial pressure, RR interval and stroke volume) at the onset of exercise.

Onset of mild lower body negative pressure induces transient change in mean arterial pressure in humans.

Mild (0 to -20 mmHg) lower body negative pressure (LBNP) has traditionally been considered to elicit reflex responses mediated by cardiopulmonary baroreceptors only, without any arterial baroreflex involvement. Mild LBNP has therefore frequently been used to study the influence of cardiopulmonary baroreceptors on the human circulatory system. In a previous study we found that mean arterial pressure (MAP) was transiently but strongly affected by rapid (0.3 s) onset and release of -20 mmHg LBNP. In the present study we tested whether MAP is also transiently affected by slow onset and release of -20 mmHg LBNP. A group of 12 subjects participated in this study, which was approved by the local Ethics Committee. Heart rate, stroke volume, cardiac output, MAP, total peripheral resistance, acral and non-acral skin blood flow, and blood flow velocity in the brachial artery were continuously recorded during the pre-LBNP period, during LBNP and during the post-LBNP period. The LBNP was gradually applied and released over a 15 s period. The main finding was that MAP was transiently but strongly affected by the gradual onset of LBNP as mild as -20 mmHg. During onset of LBNP MAP was significantly ( P=0.003) lower than MAP in the pre-LBNP period. This shows that not only the cardiopulmonary baroreceptors but also the arterial baroreceptors must be activated during mild LBNP.

Dynamic time course of hemodynamic responses after passive head-up tilt and tilt back to supine position.

Mechanisms involved in the control of arterial pressure during postural changes were studied by analysis of the dynamic time course of cardiovascular changes during head-up tilt (HUT) and tilt back to supine position (TB). Beat-to-beat values of cardiovascular variables were recorded continuously before, during, and after passive HUT to 30 degrees in seven healthy humans. Left cardiac stroke volume (SV, Doppler ultrasound), mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral conductance (TPC) were recorded. During HUT, MAP at the level of the carotid baroreceptors decreased by approximately 5 mmHg. There was a striking asymmetry between the time courses of cardiovascular changes on HUT and on TB. Adjustments generally took up to 30 s after HUT, whereas most changes were completed during the first 10 s after TB. Cardiovascular reflex adjustments of HR and TPC were more symmetrical. After HUT, SV was maintained during the first 4-6 s and then decreased steadily during the next 30 s to a stable level approximately 25% below its pretilt value. However, after TB, SV increased rapidly to its pretilt value in <10 s. This asymmetry in SV dynamics may be explained in part by a more rapid change in left cardiac filling after TB than after HUT. On TB, there must be a rapid inflow of stagnant blood from the legs, whereas venous valves will impede backward filling of veins in the lower body on HUT. In conclusion, we have revealed a characteristic asymmetry in cardiovascular responses to inverse variations in gravity forces in humans. This asymmetry can be explained in part by nonlinear, hydrodynamic factors, such as the one-way effect of venous valves in the lower part of the body.