Lower Body Negative Pressure Exposure Research Articles

Changes in Optic Nerve Head and Retinal Morphology During Spaceflight and Acute Fluid Shift Reversal

Countermeasures that reverse the headward fluid shift experienced in weightlessness have the potential to mitigate spaceflight-associated neuro-ocular syndrome. This study investigated whether use of the countermeasure lower-body negative pressure during spaceflight was associated with changes in ocular structure. To determine whether changes to the optic nerve head and retina during spaceflight can be mitigated by brief in-flight application of 25-mm Hg lower-body negative pressure. In the National Aeronautics and Space Administration's "Fluid Shifts Study," a prospective cohort study, optical coherence tomography scans of the optic nerve head and macula were obtained from US and international crew members before flight, in-flight, and up to 180 days after return to Earth. In-flight scans were obtained both under normal weightless conditions and 10 to 20 minutes into lower-body negative pressure exposure. Preflight and postflight data were collected in the seated, supine, and head-down tilt postures. Crew members completed 6- to 12-month missions that took place on the International Space Station. Data were analyzed from 2016 to 2021. Spaceflight and lower-body negative pressure. Changes in minimum rim width, optic cup volume, Bruch membrane opening height, peripapillary total retinal thickness, and macular thickness. Mean (SD) flight duration for the 14 crew members (mean [SD] age, 45 [6] years; 11 male crew members [79%]) was 214 (72) days. Ocular changes on flight day 150, as compared with preflight seated, included an increase in minimum rim width (33.8 μm; 95% CI, 27.9-39.7 μm; P < .001), decrease in cup volume (0.038 mm3; 95% CI, 0.030-0.046 mm3; P < .001), posterior displacement of Bruch membrane opening (-9.0 μm; 95% CI, -15.7 to -2.2 μm; P = .009), and decrease in macular thickness (fovea to 500 μm, 5.1 μm; 95% CI, 3.5-6.8 μm; P < .001). Brief exposure to lower-body negative pressure did not affect these parameters. Results of this cohort study suggest that peripapillary tissue thickening, decreased cup volume, and mild central macular thinning were associated with long-duration spaceflight. Acute exposure to 25-mm Hg lower-body negative pressure did not alter optic nerve head or retinal morphology, suggesting that longer durations of a fluid shift reversal may be needed to mitigate spaceflight-induced changes and/or other factors are involved.

Cardiovascular Responses to Mild Lower Body Negative Pressure during Spaceflight

IntroductionWeightlessness during spaceflight causes a chronic cephalad fluid shift that has been hypothesized to underlie numerous risks associated with spaceflight, including the development of ocular structural and functional changes and in rare cases venous thrombosis. Acute use of 25 mmHg lower body negative pressure (LBNP) during spaceflight can partially reverse this headward fluid shift and thus, may represent a promising countermeasure. However, there are limited data on how the cardiovascular system responds to sustained use of mild LBNP during spaceflight when cardiovascular deconditioning and adaptation may cause crewmembers to be more susceptible to orthostatic stressors than they would have been on Earth.PurposeThe purpose of this study was to quantify the heart rate (HR) and blood pressure response throughout ~60 minutes of exposure to 25 mmHg LBNP during spaceflight and determine if this response was augmented at later time points during 6‐month spaceflight missions.HypothesisWe hypothesized that crewmembers would experience an increase in HR during LBNP that would be sufficient to maintain mean arterial pressure (MAP) and this would not be augmented later in spaceflight.MethodsBrachial arterial pressure and HR were measured before and throughout ~60 min of 25 mmHg LBNP after ~45 days (FD45) and ~150 days (FD150) of spaceflight in 12 crewmembers. Total LBNP session times varied slightly due to logistical constraints. MAP and HR changes from baseline with LBNP exposure were analyzed with splines models. Marginal means were used for estimation and statistical comparisons across time and between flight days.ResultsBefore LBNP use, HR was 59 beats per min (BPM 95% CI: 56 – 62) and MAP was 93 mmHg (95% CI: 90 – 96). During LBNP exposure on FD45, HR increased by 9 BPM (95% CI: +7 – +10) at 15 min of exposure, and increased further to +10 BPM (95% CI: +8 – +12) at 30 min, and +11 BPM (95% CI: +9 – +14) at 45 min. On FD150, HR increased by 8 BPM (95% CI: +5 – +11) at 15 min of exposure but plateaued thereafter. MAP decreased by 5 mmHg (95% CI: ‐8 – ‐2) at 15 min and remained lower thereafter. MAP responses during ~60 min of LBNP exposure were not statistically different between FD45 and FD150. A total of 46 sessions of LBNP were successfully completed, and only a single case of mild hypotensive symptoms was reported, and this session was completed.ConclusionThese data suggest that the cardiovascular system can accommodate up to 60 min of sustained use of mild levels of LBNP during long‐duration spaceflight. There was a single report of mild hypotensive symptoms during use of LBNP by an individual who had low blood pressure prior to the start of the LBNP session. Thus, the absolute arterial blood pressure should be taken into consideration when determining if an LBNP session will be a potential challenge to the cardiovascular system during spaceflight.

Cerebral Blood Flow Pulsatility Index is Unchanged during Superimposed Lower‐Body Negative Pressure in Head‐Up Tilt in Anterior and Posterior Cerebral Circulations

Lower body negative pressure (LBNP) chambers can be utilized to experimentally-elicit reductions in blood pressure, cerebral blood flow (CBF) and associated symptoms of presyncope. There is high between-individual variability in tolerance to LBNP, however the underlying physiological responses affecting tolerance remains unclear. Pulsatility in CBF may affect LBNP tolerance, as more pulsatile flow may protect the delivery of oxygen to cerebral tissues in hypotension. We aimed to assess the pulsatility index (PI) in anterior and posterior cerebral circulations during LBNP in superimposed head-up tilt (HUT), where gravitational-induced blood volume re-distribution augments volume unloading during LBNP. We recruited and included 12 healthy male participants, and instrumented them in a custom-build integrated 45° HUT-LBNP chamber. Participants were instrumented for heart rate (HR; ECG), end-tidal CO2 (PETCO2; mouthpiece and gas analyzer),beat-by-beat mean arterial pressure (MAP; finometer), and middle and posterior cerebral artery velocity (MCAv, PCAv; transcranial Doppler ultrasound). All measures were recorded during baseline (BL) and during -50 mmHg LBNP exposure up to a maximum of 10-minutes (600s). Presyncope was defined as a 30% reduction in systolic blood pressure (i.e., investigator stop) or onset subjective symptoms (i.e., participant stop). We quantified all variables as a 30-sec mean bin during BL and the final 30-sec of LBNP prior to presyncope. MAP, MCAv and PCAv PI was calculated as systolic-diastolic/mean. LBNP tolerance time was 480.9±134.3 sec. HR increased from 72.3±10.3 (BL) to 103.0±18.2 bpm (P<0.01) during LBNP, suggesting a baroreflex response, and PETCO2 was reduced from 32.0±2.9 (BL) to 28.7±2.9 Torr (P<0.01) during LBNP, suggesting mild hyperventilation. MAP decreased from 84.8±11.3 (BL) to 76.2±14.7 mmHg (P<0.01) during LBNP, with associated reductions in mean MCAv from 52.1±15.0 to 44.3±14.5 cm/s (P<0.01), and mean PCAv from 35.5±12.6 to 29.0±9.9 cm/s (P<0.01) during LBNP. MAP PI was reduced from 0.76±0.2 to 0.59±0.02 (P<0.01) during LBNP. However, MCAv and PCAv PI were unchanged during LBNP (P=0.6 and P=0.9, respectively). Our results suggest that although MAP and MAP PI were both reduced during LBNP at pre-syncope, with associated reductions in mean MCAv and PCAv, MCAv and PCAv PI remained stable with LBNP in HUT. These findings suggest that PI in CBF variables at the cardiac frequency are not related to LBNP tolerance in healthy men.

Effect of Lower Body Negative Pressure on Phase I Cardiovascular Responses at Exercise Onset.

We hypothesised that vagal withdrawal and increased venous return interact in determining the rapid cardiac output (CO) response (phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood distribution to the heart by muscle pump action and reduce resting vagal activity. We expected a larger increase in stroke volume (SV) and smaller for heart rate (HR) at progressively stronger LBNP levels, therefore CO response would remain unchanged. To this aim ten young, healthy males performed a 50 W exercise in supine position at 0 (Control), −15, −30 and −45 mmHg LBNP exposure. On single beat basis, we measured HR, SV, and CO. Oxygen uptake was measured breath-by-breath. Phase I response amplitudes were obtained applying an exponential model. LBNP increased SV response amplitude threefold from Control to −45 mmHg. HR response amplitude tended to decrease and prevented changes in CO response. The rapid response of CO explained that of oxygen uptake. The rapid SV kinetics at exercise onset is compatible with an increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, one acting on SV, the other on HR.

Oxidative Stress During Simulated Hemorrhage Elicited by Lower Body Negative Pressure

BackgroundHemorrhage is a leading cause of potentially preventable death in both civilian and military trauma settings. Hemorrhage also elicits an oxidative stress response as a direct result of losing blood volume, or as an indirect response to ischemia‐reperfusion injury. Lower body negative pressure (LBNP) is a well validated, non‐invasive, and reproducible approach to simulate hemorrhage by inducing central hypovolemia in healthy conscious humans. The oxidative stress response to simulated hemorrhage via LBNP has not been quantified. We hypothesized that systemic markers of oxidative stress would increase with application of LBNP.Methods15 healthy human subjects (11M, 4F; 27 ± 1 y) were recruited for a step‐wise LBNP exposure to presyncope (systolic blood pressure &lt;80 mmHg or subjective presyncopal symptoms). After baseline, LBNP pressure progressively decreased every 5 minutes to −15, −30, −45, −60, −70, −80, −90, and −100 mmHg. Arterial pressure and stroke volume were measured continuously via finger photoplethysmography, and venous blood samples were collected at baseline and during the LBNP profile. Plasma samples were analyzed for F2‐isoprostanes, a global marker of oxidative stress, via gas chromatography/mass spectrometry.ResultsThe magnitude of central hypovolemia, indexed by the % change in stroke volume, ranged from a 27% to 74%. LBNP induced a −12.6 ± 2.6 % decrease in MAP (%Δ MAP) from baseline (P&lt;0.001). F2‐isporostanes increased by 28.5 ± 11.6 % (P=0.05) from baseline (24 ± 2 pg/ml) to presyncope (29 ± 3 pg/ml). The increase in F2‐isoprostanes was not associated with the decrease in MAP (r=0.05).ConclusionSimulated hemorrhage elicited by step‐wise LBNP to presyncope elicited an increase in a global marker of oxidative stress. These findings have important implications in the study of hemorrhage and potential application of targeted interventions.Support or Funding InformationFunding Source: Owens Foundation Grant and UNTHSC ICMD Junior Faculty Seed Grant.Analysis of eicosanoids (F2‐isoprostanes) were performed in the Vanderbilt University Eicosanoid Core Laboratory.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The use of negative pressure wave treatment in athlete recovery

Background: Athletes need to recover fully to maximise performance in competitive sport. Athletes who replenish more quickly and more efficiently are able to train harder and more intensely. Elite athletes subjectively report positive results using lower body negative pressure (LBNP) treatment as an alternate method for rapid recovery, restoring and improving their impaired physical state. Objective data on the efficacy are lacking.Objectives: To investigate the effect of intermittent vacuum therapy on accelerating acute recovery following an athlete’s normal daily training schedule of strenuous exercise. Objective measurements of biological markers of muscular fatigue were used to assess recovery.Methods: Twenty-two male cricket players in a randomised cross-over study were divided into a treatment and control group respectively. Following a one-hour high-intensity gym session, the treatment group received three 30-minute LBNP exposure sessions over three consecutive days (0, 24 and 48 hours). Blood lactate and creatine kinase biomarkers were collected to measure the recovery process. After 14 days groups were crossed over and the trial repeated.Results: Heart rate and blood pressure decreased noticeably during treatment, reverting to baseline levels after treatment. Lactate concentrations decreased in both groups after exercise termination; significantly more in the treatment (0.57±0.23 mmol/l) than control group (0.78±0.22 mmol/l), p&lt;0.001). Creatine kinase (CK) was similar in both groups. Athletes’ subjective assessments of recovery rated moderately high.Conclusion: LBNP therapy applied as treatment during routine schedule may have a systemic effect in lowering serum lactate levels, but not CK levels. Enhanced recovery of athletes is still unconfirmed.

Epinephrine Does Not Influence Baroreflex Sensitivity During Lower Body Negative Pressure to Physiological Tolerance

BackgroundThe baroreflex plays an integral role in blood pressure maintenance by altering heart rate and sympathetic activity in response to changes in arterial pressure. Baroreflex sensitivity (BRS) has been shown to decrease linearly during progressive exposure to central hypovolemia as induced by lower body negative pressure (LBNP), and can be used as an index of decompensation status during hemorrhage. Circulating epinephrine is significantly elevated during high stress situations such as hemorrhage; however, it is unclear whether epinephrine influences BRS during progressive exposure to central hypovolemia. Based on previous work, we hypothesized epinephrine would attenuate any reduction in spontaneous cardiac baroreflex sensitivity during LBNP.MethodsTen young (35±3 yrs), healthy (BMI 24±1 kg/m2) men and women (6M/4F) underwent LBNP protocols on 2 separate days consisting of a 10‐min pre‐infusion baseline, 15‐min infusion period (randomized to saline or epinephrine, 0.1 μg/kg/min), 10‐min post‐infusion baseline, and 5 minutes of LBNP at −15, −30, −45, −60, −70, and −80 mmHg until the onset of presyncope (range= −30 to −80 mmHg). Presyncope was defined as a rapid decrease in systolic blood pressure greater than 15 mmHg, systolic blood pressure less than 80 mmHg, bradycardia, or voluntary termination due to presyncopal symptoms. Heart rate (HR; electrocardiogram) and blood pressure (BP; radial arterial catheter) were recorded continuously. Spontaneous cardiac BRS was determined using the sequence method (WinCPRS). Data are reported from both 10‐min baselines and from 1 minute at 20, 40, 60, 80, and 100 percent of each individual's total LBNP exposure time.ResultsWe observed no significant differences in total exposure time (1475±150 vs. 1415±79s; p=0.69) or cumulative stress index (820±135 vs. 699±69 min*mmHg; p=0.37) between saline and epinephrine visits, respectively. Baroreflex sensitivity did not change during post‐infusion baselines (ΔDown‐Down =−2±1 vs. −2±2 ms/mmHg; saline vs. epinephrine, respectively; p=0.09). Baroreflex sensitivity was significantly reduced with LBNP (p&lt;0.01 main effect of LBNP). There was no difference between the change in baroreflex sensitivity during LBNP with saline or epinephrine infusion (ΔDown‐Down =−14±4 vs. −8±4 ms/mmHg, p=0.17).ConclusionsConsistent with previous work, spontaneous cardiac baroreflex sensitivity fell during LBNP. Contrary to our hypothesis, epinephrine infusion did not attenuate the fall in spontaneous cardiac baroreflex sensitivity observed during simulated blood loss. Because epinephrine did not alter the effect of LBNP on BRS, these data suggest that BRS may accurately reflect decompensation status during traumatic hemorrhage independent of elevated circulating epinephrine.Support or Funding InformationUS Army Medical Research and Materiel Command Contract W81XWH‐13‐2‐0038

The use of negative pressure wave treatment in athlete recovery

Background: Athletes need to recover fully to maximise performance in competitive sport. Athletes who replenish more quickly and more efficiently are able to train harder and more intensely. Elite athletes subjectively report positive results using lower body negative pressure (LBNP) treatment as an alternate method for rapid recovery, restoring and improving their impaired physical state. Objective data on the efficacy are lacking. Objectives: To investigate the effect of intermittent vacuum therapy on accelerating acute recovery following an athlete’s normal daily training schedule of strenuous exercise. Objective measurements of biological markers of muscular fatigue were used to assess recovery. Methods: Twenty-two male cricket players in a randomised cross-over study were divided into a treatment and control group respectively. Following a one-hour high-intensity gym session, the treatment group received three 30-minute LBNP exposure sessions over three consecutive days (0, 24 and 48 hours). Blood lactate and creatine kinase biomarkers were collected to measure the recovery process. After 14 days groups were crossed over and the trial repeated. Results: Heart rate and blood pressure decreased noticeably during treatment, reverting to baseline levels after treatment. Lactate concentrations decreased in both groups after exercise termination; significantly more in the treatment (0.57±0.23 mmol/l) than control group (0.78±0.22 mmol/l), p<0.001). Creatine kinase (CK) was similar in both groups. Athletes’ subjective assessments of recovery rated moderately high. Conclusion: LBNP therapy applied as treatment during routine schedule may have a systemic effect in lowering serum lactate levels, but not CK levels. Enhanced recovery of athletes is still unconfirmed.

Subjective visual vertical in erect/supine subjects and under microgravity: effects of lower body negative pressure

Perception of the subjective visual vertical (SVV) is mainly based on the contributions from the visual, vestibular, and proprioceptive systems, and participates to the process of spatial orientation in relation to the surrounding environment and to the gravito-inertial force. The SVV can be significantly influenced by the presence of a displaced visual field, as in the case of the rod and frame test (RFT). A series of studies showed the effects of haematic mass shifts to and from the lower limbs on SVV, due to visceral mechanoreceptors (VM) located at the level of the kidneys and of the thorax. These sensors may be artificially activated with a lower body negative pressure (LBNP) device. In this study, the role of visual and VM cues to orientation perception have been evaluated using the RFT and the LBNP devices under a microgravity environment. A preliminary investigation was conducted in a sample of military pilots to develop a RFT protocol to be used in microgravity environments. This protocol was adopted to evaluate the contribution of VM to the SVV in a cosmonaut before, during and after a 10 day space flight, with and without concurrent activation of LBNP. The same test sequence, including LBNP exposure, was repeated a few months later on Earth on the same subject. As expected, the influence of the frame on rod positioning was statistically significant in all test conditions. During the in-flight experimental step, a substantial lack of significant changes compared to the pre-flight condition was observed. Moreover, substantially no effects due to LBNP were observed. A mild rod displacement from the body axis was detected under microgravity compared to the pre-flight recording. Such a finding was in part reduced during LBNP. The same findings were observed during the post-flight repetition of the experiment. Our results showed an absence in this subject of significant effects on the RFT due to microgravity. In conclusion, no effects from his VM on the RFT and minor changes in the SVV could be detected.

Oxygen saturation determined from deep muscle, not thenar tissue, is an early indicator of central hypovolemia in humans

To compare the responses of noninvasively measured tissue oxygen saturation (StO2) and calculated muscle oxygen tension (PmO2) to standard hemodynamic variables for early detection of imminent hemodynamic instability during progressive central hypovolemia in humans. Prospective study. Research laboratory. Sixteen healthy human volunteers. Progressive lower body negative pressure (LBNP) to onset of cardiovascular collapse. Noninvasive measurements of blood pressures, heart rate, and stroke volume were obtained during progressive LBNP with simultaneous assessments of StO2, PmO2, and muscle oxygen saturation (SmO2). Forearm SmO2 and PmO2 were determined with a novel near infrared spectroscopic measurement device (UMMS) and compared with thenar StO2 measured by a commercial device (HT). All values were normalized to the duration of LBNP exposure required for cardiovascular collapse in each subject (i.e., LBNP maximum). Stroke volume was significantly decreased at 25% of LBNP maximum, whereas blood pressure was a late indicator of imminent cardiovascular collapse. PmO2 (UMMS) was significantly decreased at 50% of maximum LBNP while SmO2 (UMMS) decreased at 75% of maximum LBNP. Thenar StO2 (HT) showed no statistical change throughout the entire LBNP protocol. Spectroscopic assessment of forearm muscle PO2 and SmO2 provides noninvasive and continuous measures that are early indicators of impending cardiovascular collapse resulting from progressive reductions in central blood volume.

Inspiratory resistance delays the reporting of symptoms with central hypovolemia: association with cerebral blood flow

We tested the hypothesis that breathing through an inspiratory threshold device (ITD) during progressive central hypovolemia would protect cerebral perfusion and attenuate the reporting of presyncopal symptoms. Eight human subjects were exposed to lower-body negative pressure (LBNP) until the presence of symptoms while breathing through either an active ITD (-7 cmH(2)O impedance) or a sham ITD (0 cmH(2)O). Cerebral blood flow velocity (CBFV) was measured continuously via transcranial Doppler and analyzed in both time and frequency domains. Subjects were asked to report any subjective presyncopal symptoms (e.g., dizziness, nausea) at the conclusion of each LBNP exposure. Symptoms were coincident with physiological evidence of cardiovascular collapse (e.g., hypotension, bradycardia). Breathing on the active ITD increased LBNP tolerance time (mean +/- SE) from 2,014 +/- 106 s to 2,259 +/- 138 s (P = 0.006). We compared CBFV responses at the time of symptoms during the sham ITD trial with those at the same absolute time during the active ITD trial (when there were no symptoms). While there was no difference in mean CBFV at these time points (sham, 44 +/- 4 cm/s vs. active, 47 +/- 4; P = 0.587), total oscillations (sum of high- and low-frequency spectral power) of CBFV were higher (P = 0.004) with the active ITD (45.6 +/- 10.2 cm/s(2)) than the sham ITD (22.1 +/- 5.4 cm/s(2)). We conclude that greater oscillations around the same absolute level of mean CBFV are induced by inspiratory resistance and may contribute to the delay in symptoms and cardiovascular collapse that accompany progressive central hypovolemia.

Cerebral blood flow oscillations elicited by inspiratory resistance delays the reporting of orthostatic symptoms with central hypovolemia

We tested the hypothesis that breathing through an inspiratory threshold device (ITD) during progressive central hypovolemia would increase cerebral perfusion and attenuate the reporting of symptoms. Methods: Eight human subjects were exposed to lower body negative pressure (LBNP) until the presence of presyncopal symptoms while breathing through either an active ITD (−7 cmH2O impedance) or a sham ITD (0 cmH2O). Cerebral blood flow velocity (CBFV) was measured continuously via transcranial Doppler and analyzed in both time and frequency domains. Subjects were asked to report any presyncopal symptoms (e.g., dizziness, nausea) at the conclusion of each LBNP exposure. Results: Breathing on the active ITD increased LBNP tolerance time from 2005 ± 104 s to 2254 ± 137 s (p = 0.006). We compared CBFV responses at the time of presyncopal symptoms during the sham ITD trial with those at the same absolute time during the active ITD trial (when there were no symptoms). While there was no difference in mean CBFV at these time points (sham, 49 ± 3 cm/s vs. active, 45 ± 4 cm/s; p = 0.428), total oscillations (sum of high and low frequency spectral power) of cerebral blood flow were higher (p = 0.03) with the active ITD (45.7 ± 10.2 cm/s2) than the sham ITD (22.1 ± 5.4 cm/s2). Conclusion: Greater oscillations around the same absolute level of CBFV are induced by inspiratory resistance and may account for the delay in symptoms with central hypovolemia.

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.

Hemodynamic and hormonal changes during lower body negative pressure in bedridden disabled patients

Hemodynamic responses and hormonal changes induced by lower body negative pressure (LBNP) were measured in bedridden patients with severe disabilities to identify their cardiovascular function. After a control period of 5 minutes supine, each subject underwent a LBNP test of ‐20 mmHg for 5 minutes. Disabled patients were classified into two groups: Group HI consisted of the members who had a blood pressure response to LBNP exposure similar to normal control subjects, and group H2 patients displayed a greater reduction in blood pressure than the normal response. Both disabled groups demonstrated a significantly higher level of resting heart rate as well as a smaller stroke volume and cardiac output than normal subjects. Exposure to LBNP in disabled patients produced a smaller decrement in stroke volume and cardiac output than in normal subjects. The expected increase in heart rate for the compensatory effect was not observed in the HI group, and a decreased heart rate lower than resting values was measured in the H2 group. The norepinephrine response of the disabled groups was found to be insufficient compared with normal subjects. It is suggested that cardiovascular deconditioning of disabled patients is caused not only by a decrease in total blood volume, but also by impairment of baroreflex activity both centrally and peripherally due to the patient's extremely prolonged recumbency.

Large capacity in man for effective plasma volume control in hypovolaemia via fluid transfer from tissue to blood.

Compensatory absorption of extravascular fluid from skeletal muscle and skin into the circulation in response to experimental hypovolaemia was studied by plethysmographic technique in the upper arm of man. Lower body negative pressure (LBNP) of 90 cmH2O, applied for 10 min, served to produce rapid and prominent hypovolaemic stress as indicated by prompt decrease in central blood volume (external recording of [99Tcm]erythrocyte activity) followed by marked tachycardia. The arm concomitantly showed an initial mobilization of regional blood, an increased vascular resistance, and a continuous net transcapillary fluid absorption, i.e. similar responses as reported in animals upon haemorrhage. The absorption of extravascular fluid, validated by simultaneous analyses of changes in tissue volume and in regional blood volume [99Tcm]erythrocyte activity), was rapid and averaged 0.13 ml min-1 100 ml-1 soft tissue during the 10 min of LBNP exposure. In some subjects with symptoms and signs of pronounced circulatory stress fluid was transferred twice as fast. Separate experiments indicated that the rapid fluid flux was causally linked to the existence in the studied tissue of a large transcapillary hydraulic conductance. It is concluded that man possesses a surprisingly great capacity for compensatory circulatory refill via fluid transfer from tissue to blood. The data in fact suggest that in true states of hypovolaemia as much as 500 ml might be gained into the circulation in only 10 min.

Very rapid net transcapillary fluid absorption from skeletal muscle and skin in man during pronounced hypovolaemic circulatory stress.

High levels (110-120 cmH2O) of lower body negative pressure (LBNP) were used in male volunteers (n = 7) to produce pronounced hypovolaemic circulatory stress in an attempt to reveal the potential in man for compensatory absorption of extravascular fluid from skeletal muscle and skin as studied in the upper arm by plethysmographic technique. LBNP evoked clear-cut hypovolaemic symptoms or even accidental syncope as well as a marked tachycardiac response and a significant fall in systolic blood pressure. In the studied arm there was concomitantly a very rapid net transcapillary absorption of extravascular fluid into the circulation at an average rate of 0.35 ml min-1 100 ml-1 soft tissue during 5 min of LBNP exposure. These data demonstrate an amazingly great potential to increase plasma volume by 'autotransfusion' of fluid from tissue to blood, as may be visualized by extrapolation of the data from the arm to apply to the whole mass of skeletal muscle and skin in the body. The observed absorption rate would then correspond to a total fluid gain of no less than 700 ml within a period no longer than 5 min. At present, however, there is no evidence to indicate that such impressive fluid volumes can be rapidly transferred from the extra-to the intravascular space after actual blood loss.

Circulatory and respiratory responses to lower body negative pressure in man.

Circulatory and ventilatory responses to lower body negative pressure (LBNP) were simultaneously investigated in 8 healthy men before, during, and after the application of -20, -40, and -60 mmHg pressure. Minute ventilation (VE) decreased during LBNP due to a fall in respiratory frequency with sustained tidal volume. The cardiac output (Q) was reduced in proportion to the applied LBNP exposure, while VE decreased to almost the same level at all LBNP applications. In spite of decreased VE, end-tidal PO2 and PCO2 were increased and decreased, respectively, indicating a relative alveolar hyperventilation. The ventilation equivalent for O2 (VE/VO2) increased, while the cardiac output equivalent for O2 (Q/VO2) decreased. The relation between VE/VO2 and Q/VO2 showed a significant negative correlation (r = -0.93, p less than 0.01). The veno-arterial CO2 concentration difference (CvCO2--CaCO2) increased with LBNP, due to a fall in CaCO2 with constant CvCO2. The constant CvCO2 indicated a constant tissue acid-base balance. These observations suggest the existence of a ventilatory mechanism improving the efficiency of respiration in order to compensate for the sustained LBNP depression of Q at a given gas exchange.