Application Of Lower Body Negative Pressure Research Articles

REVIEW OF LOWER BODY NEGATIVE PRESSURE APPLICATIONS TO SIMULATE +GZ-INDUCED CARDIOVASCULAR STRAIN: RESEARCH HISTORY

Introduction: In the paper, a general overview of the development and applications of l ower body negative pressure ( LBNP) technology have been provided. The article also descr ibes the LBNP designs used to investigate the relationship between tolerance to negative pressure around the lower body and tolerance to acceleration (+Gz). Methods: A systematic review of the literature on the development and application of LBNP in the sc ope not limited to the time or geography framework was explored. Searches were performed using predefined keywords and filters for LBNP (e.g., aerospace, medicine, cardiovascular, space, acceleration, Gz ). Databases such as PubMed, IEEE Xplore, ScienceDire ct, and others relevant to this field of study were selected for the search. Results: The results of the review were organized by thematic categories (LBNP development, applications and use to s imulate +Gz induced cardiovascular strain ). Syntheses of the r esults are presented, highlighting key themes and insights. Discussion and Conclusion: T he use of LBNP to simulate cardiovascular strain, typically induced by positive G forces (+Gz) in fighter jet flight, has played an important role in our understanding of the cardiovascular response to gravitational forces. This knowledge not only benefits pilots, but also has wider implications for healthcare and working conditions where individuals may face similar physiological challenges. Although numerous reports su pport the development of LBNP for space mission applications, there is no evidence for the use of LBNP to simulate accelerations greater than +1 Gz over the past two decades. However, further research in this area is still warranted.

Dynamic changes in renal sodium handling during sympathetic stimulation in healthy human males

The temporal response of changes in renal sodium reabsorption during increased renal sympathetic nerve activity has not been investigated. Central hypovolemia by application of lower-body negative-pressure (LBNP) elicits baroreceptor mediated sympathetic reflexes to maintain arterial blood pressure. We hypothesized, that during 90 min LBNP, the renal sodium retention would increase rapidly, remain increased during intervention, and return to baseline immediately after end of intervention. Methods30 young, healthy, sodium loaded, non-obese males were exposed to −15 mmHg LBNP, −30 mmHg LBNP, −15 mmHg LBNP + renin blockade or time-control (0 mmHg LBNP) for 90 min. Urine was collected every 15 min during 90 min of intervention and 60 min of recovery to identify a possible relation between time of intervention and renal response. ResultsAll intervention groups exhibited a comparable reduction in distal sodium excretion at the end of the intervention (P = 0.46 between groups; −15 mmHg: −3.1 ± 0.9 %, −30 mmHg: −2.9 ± 0.6 %, −15 mmHg + aslikiren: −1.8 ± 0.6 %). −15 mmHg+Aliskiren resulted in a slower onset, but all groups exhibited a continued reduction in sodium excretion after 1 h of recovery despite return to baseline of renin, aldosterone, diuresis and cardiovascular parameters. ConclusionSympathetic stimulation for 90 min via LBNP at −30 mmHg LBNP compared to −15 mmHg did not result in a greater response in fractional Na+ excretion, suggesting that additional baroreceptor unloading did not cause further increases in renal sodium reabsorption. Changes in distal Na+ excretion were linear with respect to time (dose) of intervention, but seem to exhibit a saturation-like effect at a level around 4 %. The lack of recovery after 1 h is also a new finding that warrants further investigation.

The Effect of Supine Cycling and Progressive Lower Body Negative Pressure on Cerebral Blood Velocity Responses.

Moderate-intensity aerobic exercise increases cerebral blood velocity (CBv) primarily due to hyperpnea-induced vasodilation; however, the integrative control of cerebral blood flow (CBF) allows other factors to contribute to vasodilation. Lower body negative pressure (LBNP) can reduce CBv, the exact LBNP-intensity required to blunt the aforementioned exercise-induced CBv response is unknown. This could hold utility for concussion recovery, allowing individuals to exercise at higher-intensities without symptom exacerbation. Thirty-two healthy adults (age: 20-33 years; 19 females) completed a stepwise maximal-exercise test to determine each participant's wattage associated with their exercise-induced maximal CBv increase. During the second visit, participants completed moderate-intensity exercise at their determined threshold, while progressive LBNP was applied at 0, -20, -40, -60, -70, -80, and ~88 Torr. Bilateral middle cerebral artery blood velocities (MCAv), mean arterial pressure (MAP), heart rate, respiratory rate, and end-tidal carbon dioxide levels were measured continuously. Two-way analysis of variance with effect sizes compared between sexes and stages. Compared to resting-supine baseline, averaged MCAv was elevated during 0 and -20 Torr LBNP (q-value>7.73; p<0.001); no differences were noted between baseline and -40 to -70 Torr (q-value<|4.24|; p>0.262). Differences were present between females and males for absolute MCAv measures (q-value>11.2; p<0.001), but not when normalized to baseline (q-value<0.03; p>0.951). Supine cycling-elicited increases in MCAv were blunted during the application of LBNP ranging from -40 to -70 Torr. The blunted CBv response demonstrates the potential benefit of allowing individuals to aerobically train (moderate-intensity supine cycling with LBNP) without exacerbating symptoms during concussion recovery.

The Effect of Upright Lower Body Negative Pressure on Muscle Activity and Hemodynamics during Exercise

Purpose: The aim of the study was to evaluate the changes that occur in parameters relating to muscle work and muscle hemodynamicsunder the influence of upright Lower Body Negative Pressure (LBNP) application during walking. Methods: 18 young females were included in this study. All 18 subjects participated in 2 trials of a 12-minute walking exercise on a treadmill equipped with a LBNP chamber, on a constant speed of 5 km/h. The first trial was executed under the application of a LBNP program (3 stages of -15, -25 and -30 mbar), while the second trial was similar, but without the activation of the negative pressure chamber. During both trials, the Vastus Lateralis (VL) muscle hemodynamic conditions were monitored continuously with a Functional Near-Infrared Spectroscopy (fNIRS) device and parallelly, VL activation was monitored via a Surface Electromyography (sEMG). Heart Rate (HR) values were recorded in the beginning and during the10th min of each trial, after which, the difference between the 2 values was calculated. Immediately after the conclusion of each trial, participants were asked to provide a score for perceived exertion using Borg CR-10 scale (10 for maximum exertion). Results: During the LBNP trial, Total Hemoglobin (tHb) and OxyHemoglobin (O2 Hb) concentrations in the Vastus Lateralis (VL), was significantly lower compared to the control (p=0.007, p=0.001), but with a significant increase rate in deoxy-hemoglobin (HHb) (p= 0.001). Tissue Saturation Index (TSI%) showed no significant alteration between trials (p= 0.668). All calculated parameters relating to work output showed a significant difference in the LBNP trial compared to control. HR was increased (p= 0.001), there were an increase in MPF and RMS amplitude in the VL (p=0.006, p &lt; 0.001, respectively) and subjects reported higher rate of perceived exertion (p=0.001). Conclusions: The application of LBNP showed elevated work characteristics, mainly on the work output and less local muscle hemodynamics. This could be a time efficient training tool for stressing the musculoskeletal system, faster improve body composition and potentially enhancing cardio respiratory fitness.

Pulling back on the push-pull effect: use of lower body negative pressure to protect against drops in cerebral perfusion during airflight manoeuvres.

Pulling back on the push-pull effect: use of lower body negative pressure to protect against drops in cerebral perfusion during airflight manoeuvres.

Coagulation changes induced by lower-body negative pressure in men and women.

We investigated whether lower-body negative pressure (LBNP) application leads to coagulation activation in whole blood (WB) samples in healthy men and women. Twenty-four women and 21 men, all healthy young participants, with no histories of thrombotic disorders and not on medications, were included. LBNP was commenced at -10 mmHg and increased by -10 mmHg every 5 min until a maximum of -40 mmHg. Recovery up to 10 min was also monitored. Blood samples were collected at baseline, at end of LBNP, and end of recovery. Hemostatic profiling included comparing the effects of LBNP on coagulation values in both men and women using standard coagulation tests, calibrated automated thrombogram, thrombelastometry, impedance aggregometry, and markers of thrombin formation. LBNP led to coagulation activation determined in both plasma and WB samples. At baseline, women were hypercoagulable compared with men, as evidenced by their shorter "lag times" and higher thrombin peaks and by shorter "coagulation times" and "clot formation times." Moreover, men were more susceptible to LBNP, as reflected in their elevated factor VIII levels and decreased lag times following LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. Women appear to be relatively hypercoagulable compared with men, but men are more susceptible to coagulation changes during LBNP. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis. NEW & NOTEWORTHY LBNP led to coagulation activation determined in both plasma and whole blood samples. At baseline, women were hypercoagulable compared with men. Men were, however, more susceptible to coagulation changes during LBNP. LBNP-induced coagulation activation was not accompanied by endothelial activation. The application of LBNP might be a useful future tool to identify individuals with an elevated risk for thrombosis, in subjects with or without history of thrombosis.

Lower Body Negative Pressure Counters Internal Jugular Vein Engorgement during Simulated Microgravity

Recent ophthalmic evaluations of seven astronauts after six‐month missions to International Space Station (ISS) show unexpected vision problems. A microgravity induced cephalad fluid shift during long‐duration ISS missions may result in cephalic venous congestion. We hypothesized that simulated microgravity would cause internal jugular vein (IJV) engorgement but application of lower‐body negative pressure (LBNP) would mitigate this response. Six normal healthy subjects volunteered for this study (mean age: 23 years) after IRB review. Cross‐sectional area (CSA) of IJV was measured using standard ultrasound procedures. Heart rate and blood pressure were measured using an automatic blood pressure device. Data were collected during the last min of each of the following conditions: sitting (5mins), supine (5mins), head‐down‐tilt (HDT) (5mins), and HDT+LBNP (10mins with LBNP of 25 mmHg). Standard onboard ultrasound software was used to calculate IJV CSA. Data are presented as mean ± SD. RMANOVA was used to determine statistical significance with p&lt;0.05. The IJV CSA significantly increased from the sitting (0.074±0.028 cm2) to the supine (0.602±0.189 cm2) posture, p=0.001. IJV CSA further increased when the subjects were positioned in the HDT position (1.034±0.263 cm2), p=0.002. However, when LBNP was activated during HDT, IJV CSA decreased (0.714±0.289 cm2) and was not significantly different from supine levels (p=0.259). Mean blood pressure and heart rate did not change significantly across all conditions. In conclusion, LBNP during simulated microgravity may reduce cephalad venous congestion. This project was supported by APS Frontiers in Physiology Fellowship (to SLB), NSBRI through NASA NCC 9‐58 (to BRM), and NASA grant NNX13AJ12G (to ARH).

Reproducibility of Near Infrared Spectroscopy (NIRS)‐Derived Peripheral Muscle Oxygenation Measurements at Rest and During Central Hypovolemia

Background Noninvasive muscle oxygen saturation (SmO2) measurements from near-infrared spectroscopy (NIRS) sensors have been demonstrated to track the severity of central hypovolemia. The reproducibility of these devices in detecting and tracking reductions in SmO2 during central hypovolemia, however, has not been quantified. Methods 27 healthy human subjects (11 F, 16 M) were instrumented with a CareGuide 1100 muscle NIRS sensor (Reflectance Medical Inc.) on their right flexor carpi ulnaris muscle for assessment of SmO2, tissue pH, and the microcirculatory index (MCI, an estimate of peripheral resistance). Subjects were exposed to two trials (蠅 4 weeks intervening) of lower body negative pressure (LBNP) applied at a rate of 3 mmHg/min until presyncope or voluntary termination. SmO2, pH, and MCI were compared to stroke volume (SV) responses derived from a non-invasive arterial pressure waveform. Results SV decreased by ~50% for both trials (p=0.94), and time to LBNP termination was similar (p=0.36). Both baseline and maximal SmO2, pH, and MCI were statistically indistinguishable between the two trials (p蠅0.17). Responses of SmO2, pH, and MCI were highly correlated between trials (r蠅0.91; p蠄0.004; slopes蠅0.77), and each parameter tracked the reduction in SV (table). Conclusions NIRS-derived measurements of SmO2, pH, and MCI were reproducible during central hypovolemia elicited by continuous application of LBNP. These findings support the use of SmO2 to monitor blood loss. Funding Source: US Army MRMC Trial 1 Trial 2 R2 P-Value Slope R2 P-Value Slope SmO2 vs. SV 0.94 <0.001 0.09 0.97 <0.001 0.12 pH vs. SV 0.89 0.001 0.001 0.91 <0.001 0.001 MCI vs. SV 0.82 <0.001 0.31 0.96 <0.001 0.30

Effects of intermittent lower-body negative pressure on recovery after exercise-induced muscle damage.

It has been reported in practice that the application of lower-body negative pressure (LBNP) to elite athletes during periods of intense training can help aid recovery. To examine the effects of LBNP on biochemical, pain, and performance parameters during a 5-d recovery period after a damaging plyometric-exercise bout. Randomized controlled study. 24 healthy young female adults were randomly allocated into 2 groups. Before and 1, 24, 48, and 96 h after the damaging exercise for hamstrings (50 drop jumps and 50 leg curls), participants underwent a series of tests (blood samples, pain sensation, countermovement jump, maximal isometric torque production, maximal explosive isometric torque production, and 10-m sprint). After the damaging exercise, the experimental group was exposed to intermittent LBNP therapy daily for 60 min. There was a statistically significant interaction (P<.05) between the experimental and control groups for maximal strength, explosive strength, pain sensation, and vertical jumps (maximal power and force). No statistically significant interaction was present for the biochemical markers, jump height, and 100-m sprint. LBNP therapy could improve recovery by limiting the loss in muscle strength and power and limiting the presence of pain.

Thirst response to acute hypovolaemia in healthy women and women prone to vasovagal syncope

The present study measured self-perceived thirst and plasma angiotensin II (ATII) concentrations during graded hypovolaemic stress, induced by lower body negative pressure (LBNP), to elucidate the dependence of thirst on haemodynamics. A total of 24 women aged between 20 and 36 (mean age, 23) years rated their thirst on a visual analogue scale, graded from 0 to 100, when LBNP of 20, 30 and 40mmHg was applied. Half of the women had a history of vasovagal syncope (VVS). The results showed that the thirst score increased three-fold when LBNP was applied, from 11 (median; 25th–75th percentiles, 9–25) to 34 (27–53; P<0.001). The women in the VVS group had twice as great an increase as those without a history of VVS (P<0.02). The plasma ATII concentration increased significantly in response to LBNP, both in the VVS group and in the control group, but the changes did not correlate with thirst. Application of LBNP decreased systolic and mean arterial pressures, cardiac output and pulse pressure (P<0.001 for all), but thirst correlated only with increase in heart rate and, independently, with reduction of mean arterial pressure. In conclusion, thirst and ATII increase in response to hypovolaemic stress, but are not statistically related. The haemodynamic parameter that was most strongly related to thirst was tachycardia.

Divergent roles of plasma osmolality and the baroreflex on sweating and skin blood flow

Plasma hyperosmolality and baroreceptor unloading have been shown to independently influence the heat loss responses of sweating and cutaneous vasodilation. However, their combined effects remain unresolved. On four separate occasions, eight males were passively heated with a liquid-conditioned suit to 1.0°C above baseline core temperature during a resting isosmotic state (infusion of 0.9% NaCl saline) with (LBNP) and without (CON) application of lower-body negative pressure (-40 cmH2O) and during a hyperosmotic state (infusion of 3.0% NaCl saline) with (LBNP + HYP) and without (HYP) application of lower-body negative pressure. Forearm sweat rate (ventilated capsule) and skin blood flow (laser-Doppler), as well as core (esophageal) and mean skin temperatures, were measured continuously. Plasma osmolality increased by ∼10 mosmol/kgH2O during HYP and HYP + LBNP conditions, whereas it remained unchanged during CON and LBNP (P ≤ 0.05). The change in mean body temperature (0.8 × core temperature + 0.2 × mean skin temperature) at the onset threshold for increases in cutaneous vascular conductance (CVC) was significantly greater during LBNP (0.56 ± 0.24°C) and HYP (0.69 ± 0.36°C) conditions compared with CON (0.28 ± 0.23°C, P ≤ 0.05). Additionally, the onset threshold for CVC during LBNP + HYP (0.88 ± 0.33°C) was significantly greater than CON and LBNP conditions (P ≤ 0.05). In contrast, onset thresholds for sweating were not different during LBNP (0.50 ± 0.18°C) compared with CON (0.46 ± 0.26°C, P = 0.950) but were elevated (P ≤ 0.05) similarly during HYP (0.91 ± 0.37°C) and LBNP + HYP (0.94 ± 0.40°C). Our findings show an additive effect of hyperosmolality and baroreceptor unloading on the onset threshold for increases in CVC during whole body heat stress. In contrast, the onset threshold for sweating during heat stress was only elevated by hyperosmolality with no effect of the baroreflex.

The microcirculatory response to compensated hypovolemia in a lower body negative pressure model

The objective of the present study was to test the hypothesis that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation would be associated with decreased peripheral microcirculatory diffusion and convection properties and, consequently, decreased tissue oxygen carrying capacity and tissue oxygenation. Furthermore, we evaluated the impact of hypovolemia-induced microcirculatory alterations on resting tissue oxygen consumption. To this end, 24 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol of which 14 reached the end of the protocol. At baseline and at LBNP=−60mmHg, sidestream dark field (SDF) images of the sublingual microcirculation were acquired to measure microvascular density and perfusion; thenar and forearm tissue hemoglobin content (THI) and tissue oxygenation (StO2) were recorded using near-infrared spectroscopy (NIRS); and a vascular occlusion test (VOT) was performed to assess resting tissue oxygen consumption rate. SDF images were analyzed for total vessel density (TVD), perfused vessel density (PVD), the microvascular flow index (MFI), and flow heterogeneity (MFIhetero). We found that application of LBNP resulted in: 1) a significantly decreased microvascular density (PVD) and perfusion (MFI and MFIhetero); 2) a significantly decreased THI and StO2; and 3) an unaltered resting tissue oxygen consumption rate. In conclusion, using SDF imaging in combination with NIRS we showed that controlled, adequately compensated, central hypovolemia in subjects with intact autoregulation is associated with decreased microcirculatory diffusion (PVD) and convection (MFI and MFIhetero) properties and, consequently, decreased tissue oxygen carrying capacity (THI) and tissue oxygenation (StO2). Furthermore, using a VOT we found that resting tissue oxygen consumption was maintained under conditions of adequately compensated central hypovolemia.

Multi-site and multi-depth near-infrared spectroscopy in a model of simulated (central) hypovolemia: lower body negative pressure

PurposeTo test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15–2.5 and 25–2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP).MethodsThe study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, −20, −40, −60, −80 and −100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS.ResultsThe main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI.ConclusionsNIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-2128-6) contains supplementary material, which is available to authorized users.

Muscle sympathetic nerve activity during intense lower body negative pressure to presyncope in humans

Activation of sympathetic efferent traffic is essential to maintaining adequate arterial pressures during reductions of central blood volume. Sympathetic baroreflex gain may be reduced, and muscle sympathetic firing characteristics altered with head-up tilt just before presyncope in humans. Volume redistributions with lower body negative pressure (LBNP) are similar to those that occur during haemorrhage, but limited data exist describing arterial pressure-muscle sympathetic nerve activity (MSNA) relationships during intense LBNP. Responses similar to those that occur in presyncopal subjects during head-up tilt may signal the beginnings of cardiovascular decompensation associated with haemorrhage. We therefore tested the hypotheses that intense LBNP disrupts MSNA firing characteristics and leads to a dissociation between arterial pressure and sympathetic traffic prior to presyncope. In 17 healthy volunteers (12 males and 5 females), we recorded ECG, finger photoplethysmographic arterial pressure and MSNA. Subjects were exposed to 5 min LBNP stages until the onset of presyncope. The LBNP level eliciting presyncope was denoted as 100% tolerance, and then data were assessed relative to this normalised maximal tolerance by expressing LBNP levels as 80, 60, 40, 20 and 0% (baseline) of maximal tolerance. Data were analysed in both time and frequency domains, and cross-spectral analyses were performed to determine the coherence, transfer function and phase angle between diastolic arterial pressure (DAP) and MSNA. DAP-MSNA coherence increased progressively and significantly up to 80% maximal tolerance. Transfer functions were unchanged, but phase angle shifted from positive to negative with application of LBNP. Sympathetic bursts fused in 10 subjects during high levels of LBNP (burst fusing may reflect modulation of central mechanisms, an artefact arising from our use of a 0.1 s time constant for integrating filtered nerve activity, or a combination of both). On average, arterial pressures and MSNA decreased significantly the final 20 s before presyncope (n = 17), but of this group, MSNA increased in seven subjects. No linear relationship was observed between the magnitude of DAP and MSNA changes before presyncope (r = 0.12). We report three primary findings: (1) progressive LBNP (and presumed progressive arterial baroreceptor unloading) increases cross-spectral coherence between arterial pressure and MSNA, but sympathetic baroreflex control is reduced before presyncope; (2) withdrawal of MSNA is not a prerequisite for presyncope despite significant decreases of arterial pressure; and (3) reductions of venous return, probably induced by intense LBNP, disrupt MSNA firing characteristics that manifest as fused integrated bursts before the onset of presyncope. Although fusing of integrated sympathetic bursts may reflect a true physiological compensation to severe reductions of venous return, duplication of this finding utilizing shorter time constants for integration of the nerve signal is required.

Changes in Pulse Character andMental Status Are Late Responses to Central Hypovolemia

Objective. Manual assessment of radial arterial pulse character remains an important determinant of physiological status in military andcivilian casualties. This study hypothesized that changes in radial pulse character andmental status (presyncopal symptoms) in humans occur only during the later stages of progressive reductions in central blood volume in close association with systolic blood pressure (SBP). Methods. Pulse character (i.e., normal, weak, absent), estimated stroke volume (SV), SBP, anddiastolic blood pressure were measured continuously during baseline supine rest andduring progressive reductions of central blood volume to cardiovascular collapse with application of lower body negative pressure (LBNP) in 19 healthy human volunteer subjects. Results. LBNP resulted in a progressive reduction in SV. At early stages of LBNP, both radial pulse character andSBP were well-maintained. Although both radial pulse character andSBP decreased with subsequent increases in LBNP, these changes occurred only after an approximate 55% reduction in SV andwere associated with the onset of presyncopal symptoms. Changes in mental status did not occur until the point of cardiovascular collapse. Conclusions. In this model of progressive central hypovolemia secondary to application of LBNP in humans, radial pulse character score decreased in concert andwas highly correlated with decreases in SBP. In support of our hypothesis, changes in pulse character, SBP, andmental status occurred only after significant reductions in SV, suggesting that these standard vital signs may not be early indicators of central hypovolemia.

Effect of Exercise Intensity on Mild Rhythmic-handgrip-exercise-Induced functional Sympatholysis

This study attempts to clarify whether intensity of exercise influences functional sympatholysis during mild rhythmic handgrip exercise (RHG). We measured muscle oxygenation in both exercising and non-exercising muscle in the same arm in 11 subjects using near infrared spectroscopy (NIRS), heart rate, and blood pressure. We used the total labile signal to assess the relative muscle oxygenation by occlusion for 6 min. Subjects performed RHG (20 times/min) for 6 min at 10%, 20%, and 30% of maximal voluntary contraction (MVC) at random. We used a non-hypotensive lower body negative pressure (LBNP) of 220 mmHg for 2 min to elicit reproducible enhancement in muscle sympathetic nerve activity (MSNA) at rest and during RHG. LBNP caused decreases of 16.4% and 17.7% of the level of muscle oxygenation at rest (pre) in exercising (forearm) and non-exercising (upper arm) muscle respectively. Muscle oxygenation in non-exercising muscle with the application of LBNP during RHG did not change significantly at each intensity. In contrast, the decrease in muscle oxygenation in exercising muscle attenuated progressively as exercise intensity increased (10% MVC 8.8+/-2.8%, 20% MVC 7.1+/-2.0%, 30% MVC 4.6+/-3.0%), when LBNP was applied during RHG. The attenuation of the decrease in muscle oxygenation due to LBNP during RHG at 10%, 20%, and 30% was significantly different from that at rest (p<0.01). These findings indicate that functional sympatholysis during mild RHG might be attributed to exercise intensity.

R‐wave Amplitude in Lead II of an Electrocardiograph Correlates with Central Hypovolemia in Human Beings

Previous animal and human experiments have suggested that reduction in central blood volume either increases or decreases the amplitude of R waves in various electrocardiograph (ECG) leads depending on underlying pathophysiology. In this investigation, we used graded central hypovolemia in adult volunteer subjects to test the hypothesis that moderate reductions in central blood volume increases R-wave amplitude in lead II of an ECG. A four-lead ECG tracing, heart rate (HR), estimated stroke volume (SV), systolic blood pressure, diastolic blood pressure, and mean arterial pressure were measured during baseline supine rest and during progressive reductions of central blood volume to an estimated volume loss of >1,000 mL with application of lower-body negative pressure (LBNP) in 13 healthy human volunteer subjects. Lower-body negative pressure resulted in a significant progressive reduction in central blood volume, as indicated by a maximal decrease of 65% in SV and maximal elevation of 56% in HR from baseline to -60 mm Hg LBNP. R-wave amplitude increased (p < 0.0001) linearly with progressive LBNP. The amalgamated correlation (R2) between average stroke volume and average R-wave amplitude at each LBNP stage was -0.989. These results support our hypothesis that reduction of central blood volume in human beings is associated with increased R-wave amplitude in lead II of an ECG.

A model of orthostatic hypotension in the conscious monkey using lower body negative pressure

Introduction: Methods most commonly used for detecting susceptibility to orthostatic hypotension in humans include head-up tilt and the application of lower body negative pressure (LBNP). The objective of this study was to evaluate the use of LBNP for detecting drug-induced changes in susceptibility to orthostatic hypotension in conscious monkeys ( Macaca fascicularis). Methods: Orthostatic responses were produced using an airtight chamber, which sealed around the stomach (umbilical area) and enclosed the lower body, to which were applied successive decrements of 10 mmHg chamber pressure every 5 min until the orthostatic response was observed. Cardiovascular measurements, involving arterial pressures, heart rate, and left ventricular pressures were recorded. The hypotensive agents prazosin and minoxidil were administered to evaluate the ability of the procedure to detect drug-induced changes in the susceptibility to orthostatic hypotension. Results: A rapid decrease in systolic arterial pressure of > 20 mmHg occurring within a 30 s time period was determined to be the best indicator of an orthostatic response. The application of LBNP produced an orthostatic response in all monkeys and on all occasions (100% response). The onset, rate and magnitude of the decrease in systolic blood pressure were also consistent for each monkey. Prazosin (≥ 0.16 mg/kg, iv) produced an increase in the susceptibility to the orthostatic response, whereas minoxidil (10 mg/kg, po) had no effect. These results are consistent with previous findings in humans, where similar decreases in arterial pressures occur following the administration of prazosin and minoxidil, whereas increased susceptibility to orthostatic hypotension only occurs with prazosin. Discussion: The results of this study demonstrate that the application of the LBNP is a reliable method for producing an orthostatic hypotensive response in conscious monkeys. In addition, the use of positive (prazosin) and negative (minoxidil) controls demonstrated that the use of LBNP is a valid method for evaluating the effect of drug treatment on susceptibility to orthostatic hypotension.

Plasma hyperosmolality augments peripheral vascular response to baroreceptor unloading during heat stress

The aim of this study was to elucidate the interactive effect of central hypovolemia and plasma hyperosmolality on regulation of peripheral vascular response and AVP secretion during heat stress. Seven male subjects were infused with either isotonic (0.9%; NOSM) or hypertonic (3.0%; HOSM) NaCl solution and then heated by perfusing 42 degrees C (heat stress; HT) or 34.5 degrees C water (normothermia; NT) through water perfusion suits. Sixty minutes later, subjects were exposed to progressive lower body negative pressure (LBNP) to -40 mmHg. Plasma osmolality (P(osmol)) increased by approximately 11 mosmol/kgH(2)O in HOSM conditions. The increase in esophageal temperature before LBNP was much larger in HT-HOSM (0.90 +/- 0.09 degrees C) than in HT-NOSM (0.30 +/- 0.07 degrees C) (P < 0.01) because of osmotic inhibition of thermoregulation. During LBNP, mean arterial pressure was well maintained, and changes in thoracic impedance and stroke volume were similar in all conditions. Forearm vascular conductance (FVC) before application of LBNP was higher in HT than in NT conditions (P < 0.001) and was not influenced by P(osmol) within the thermal conditions. The reduction in FVC at -40 mmHg in HT-HOSM (-9.99 +/- 0.96 units; 58.8 +/- 4.1%) was significantly larger than in HT-NOSM (-6.02 +/- 1.23 units; 44.7 +/- 8.1%) (P < 0.05), whereas the FVC response was not different between NT-NOSM and NT-HOSM. Plasma AVP response to LBNP did not interact with P(osmol) in either NT or HT conditions. These data indicate that there apparently exists an interactive effect of P(osmol) and central hypovolemia on the peripheral vascular response during heat stress, or peripheral vasodilated conditions, but not in normothermia.

Increased hypoxic ventilatory response during hypovolemic stress imposed through head-up-tilt and lower-body negative pressure.

The aim of this study was to quantify the influence of head-up-tilt (HUT) on the isocapnic hypoxic ventilatory response (HVR) in man, and to investigate the effect of orthostatic blood shifts separately from other gravitational effects by the application of lower-body negative pressure (LBNP) with subjects in a horizontal position. HVR was measured in 15 subjects during passive HUT from 0 degrees to 85 degrees as well as during -7 degrees head-down-tilt and while they were in a sitting position. In a subgroup of eight subjects the effect of 85 degrees HUT was compared to a corresponding LBNP of -70 mbar on HVR. Moreover, by imposing graded HUT (7 degrees, 15 degrees, 30 degrees, 50 degrees) and LBNP (-15, -30 mbar) we studied the effect of low-level orthostatic stress on HVR. Ventilation, end-tidal partial pressure of CO2, heart rate and blood pressure were recorded continuously for 1 min before, and during HVR. HVR was significantly increased by approximately equal to 50% through both 85 degrees HUT and -70 mbar LBNP as compared to 0 degrees and 0 mbar, respectively, at unchanged mean arterial pressure. Low-level HUT and LBNP had no effect on HVR. It was concluded that the orthostatic HVR increase may be attributable to caudal blood shifts (i.e., central hypovolemia). This HVR increase requires a pronounced hypovolemic stress but no decrease in arterial blood pressure. It is suggested that a central interaction of arterial and cardiopulmonary baroreceptors is underlying this response. Their separate contribution remains to be assessed.