Lower Body Negative Pressure Level Research Articles

AI-Enabled Advanced Development for Assessing Low Circulating Blood Volume for Emergency Medical Care: Comparison of Compensatory Reserve Machine-Learning Algorithms.

The application of artificial intelligence (AI) has provided new capabilities to develop advanced medical monitoring sensors for detection of clinical conditions of low circulating blood volume such as hemorrhage. The purpose of this study was to compare for the first time the discriminative ability of two machine learning (ML) algorithms based on real-time feature analysis of arterial waveforms obtained from a non-invasive continuous blood pressure system (Finometer®) signal to predict the onset of decompensated shock: the compensatory reserve index (CRI) and the compensatory reserve metric (CRM). One hundred ninety-one healthy volunteers underwent progressive simulated hemorrhage using lower body negative pressure (LBNP). The least squares means and standard deviations for each measure were assessed by LBNP level and stratified by tolerance status (high vs. low tolerance to central hypovolemia). Generalized Linear Mixed Models were used to perform repeated measures logistic regression analysis by regressing the onset of decompensated shock on CRI and CRM. Sensitivity and specificity were assessed by calculation of receiver-operating characteristic (ROC) area under the curve (AUC) for CRI and CRM. Values for CRI and CRM were not distinguishable across levels of LBNP independent of LBNP tolerance classification, with CRM ROC AUC (0.9268) being statistically similar (p = 0.134) to CRI ROC AUC (0.9164). Both CRI and CRM ML algorithms displayed discriminative ability to predict decompensated shock to include individual subjects with varying levels of tolerance to central hypovolemia. Arterial waveform feature analysis provides a highly sensitive and specific monitoring approach for the detection of ongoing hemorrhage, particularly for those patients at greatest risk for early onset of decompensated shock and requirement for implementation of life-saving interventions.

Tolerance to Central Hypovolemia Is Greater Following Caffeinated Coffee Consumption in Habituated Users.

We investigated the influence of caffeinated coffee consumption on cardiovascular responses and tolerance to central hypovolemia in individuals habituated to caffeine. Thirteen participants completed three trials, consuming caffeinated coffee, decaffeinated coffee or water before exposure to central hypovolemia via lower body negative pressure (LBNP) to pre syncope. Tolerance to central hypovolemia was quantified as cumulative stress index (CSI: LBNP level multiplied by time; mmHg × min). Prior to the consumption of caffeinated coffee, decaffeinated coffee, and water, heart rate (HR: 62 ± 10, 63 ± 9 and 61 ± 8 BPM, respectively), stroke volume (SV: 103 ± 23, 103 ± 17 and 102 ± 18 mL/beat, respectively), and total peripheral resistance (TPR: 14.2 ± 3.0, 14.0 ± 3.0, and 14.3 ± 2.7 mmHg/L/min, respectively), were not different between trials (all P > 0.05). Mean arterial pressure (MAP) increased following consumption of all drinks (Post Drink) (Caffeinated coffee: from 86 ± 8 to 97 ± 7; Decaffeinated coffee: from 88 ± 10 to 94 ± 7; and Water: from 87 ± 10 to 96 ± 6 mmHg; all P = 0.0001) but was not different between trials (P = 0.247). During LBNP, HR increased (P = 0.000) while SV decreased (P = 0.000) relative to post drink values and TPR as unchanged (P = 0.109). HR, SV, and TPR were not different between trials (all P > 0.05). MAP decreased at pre syncope in all trials (60 ± 5, 60 ± 7, and 61 ± 6 mmHg; P < 0.001). LBNP tolerance was greater following caffeinated coffee (914 ± 309 mmHg × min) relative to decaffeinated coffee and water (723 ± 336 and 769 ± 337 mmHg × min, respectively, both P < 0.05). Tolerance to central hypovolemia was greater following consumption of caffeinated coffee in habituated users.

Differentiating compensatory mechanisms associated with low tolerance to central hypovolemia in women.

Women generally display lower tolerance to acute central hypovolemia than men. The measurement of compensatory reserve (CRM) is a novel metric that provides information about the sum total of all mechanisms that together work to compensate for the relative blood volume deficit. Hemodynamic decompensation occurs with depletion of the CRM (i.e., 0% CRM). In the present study, we hypothesized that the lower tolerance to progressive central hypovolemia reported in women can be explained by a faster reduction rate in CRM compared with men rather than sex differences in absolute integrated compensatory responses. Continuous, noninvasive measures of CRM were collected from 208 healthy volunteers (107 men and 85 women) who underwent progressive stepwise central hypovolemia induced by lower body negative pressure to the point of presyncope. Comparisons revealed shorter ( P < 0.01) times in female participants compared with male participants to reach 30% and 0% CRM. Similarly, the lower body negative pressure level, represented by the cumulative stress index, was less at 30% and 0% CRM in women compared with men ( P < 0.01). Changes in hemodynamic responses and frequency-domain data (oscillations in cerebral blood flow velocity and mean arterial blood pressure) were similar between men and women at 0% CRM ( P > 0.05). We conclude that compensatory responses to central hypovolemia in women were similar to men but were depleted at a faster rate compared with men. The earlier depletion of the compensatory reserve in women appears to be influenced by failure to maintain adequate cerebral oxygen delivery. NEW & NOTEWORTHY We compared hemodynamic and metabolic responses in men and women to experimentally controlled reductions in central blood volume at physiologically equivalent levels of compensatory reserve. We corroborated previous findings that females have lower tolerance to central hypovolemia than males but demonstrated for the first time that compensatory responses are similar. Our findings suggest lower tolerance to central hypovolemia in women results from reaching critical cerebral delivery of oxygen faster than men.

Small reductions in skin temperature after onset of a simulated hemorrhagic challenge improve tolerance in exercise heat-stressed individuals.

We investigated whether small reductions in skin temperature 60 s after the onset of a simulated hemorrhagic challenge would improve tolerance to lower body negative pressure (LBNP) after exercise heat stress. Eleven healthy subjects completed two trials (High and Reduced). Subjects cycled at ~55% maximal oxygen uptake wearing a warm water-perfused suit until core temperatures increased by ~1.2°C before lying supine and undergoing LBNP to presyncope. LBNP tolerance was quantified as cumulative stress index (CSI; product of each LBNP level multiplied by time; mmHg·min). Skin temperature was similarly elevated from baseline before LBNP and remained elevated 60 s after the onset of LBNP in both High (37.72 ± 0.52°C) and Reduced (37.95 ± 0.54°C) trials (both P < 0.0001). At 60%CSI skin temperature remained elevated in the High trial (37.51 ± 0.56°C) but was reduced to 34.97 ± 0.72°C by the water-perfused suit in the Reduced trial ( P < 0.0001 between trials). Cutaneous vascular conductance was not different between trials [High: 1.57 ± 0.43 vs. Reduced: 1.39 ± 0.38 arbitrary units (AU)/mmHg; P = 0.367] before LBNP but decreased to 0.67 ± 0.19 AU/mmHg at 60%CSI in the Reduced trial while remaining unchanged in the High trial ( P = 0.002 between trials). CSI was higher in the Reduced (695 ± 386 mmHg·min) relative to the High (441 ± 290 mmHg·min; P = 0.023) trial. Mean arterial pressure was not different between trials at presyncope (High: 62 ± 10 vs. Reduced: 62 ± 9 mmHg; P = 0.958). Small reductions in skin temperature after the onset of a simulated hemorrhagic challenge improve LBNP tolerance after exercise heat stress. This may have important implications regarding treatment of an exercise heat-stressed individual (e.g., soldier) who has experienced a hemorrhagic injury.

The Effect of Aging and Rapid Saline Infusion on Compensatory Reserve during Whole‐Body Passive Heat Stress

The compensatory reserve is defined as the physiological capacity to compensate for reductions in central blood volume. It is measured by a machine learning algorithm, called CRI, which analyzes continuous changes in the features of a photoplethysmographic signal obtained by finger pulse oximetry. The purpose of this study was 2‐fold. First, we examined the effect of healthy aging on compensatory reserve during normothermic and heat stress conditions. Second, we examined the effect of rapid saline infusion during heat stress on compensatory reserve. Eleven young (6 males/5 females; mean ± SD: age, 25 ± 4 years; height, 165 ± 6 cm; weight, 63 ± 9 kg) and ten aged (4 males/6 females; age, 69 ± 4 years; height, 165 ± 9 cm; weight, 68 ± 9 kg) adults were exposed to central hypovolemia via 15 and 30 mmHg of lower‐body negative pressure (LBNP) under normothermic and heat stress (increase in core temperature of 1.5°C) conditions. Approximately 10 min after the heat stress LBNP challenge, warm saline was rapidly infused (15 ml/kg in ~6 min) while subjects remained hyperthermic. Absolute CRI values (Table) range between 0 and 1, where 0 represents little to no reserve for cardiovascular compensation and 1 represents maximal physiological reserve to compensate for central hypovolemia. Under normothermic conditions, an age × LBNP level interaction was observed (P&lt;0.01). Relative to baseline, CRI was reduced during 15 mmHg LBNP in young (P&lt;0.01) but not aged (P=0.21) adults. During 30 mmHg LBNP, CRI was reduced in both groups (P≤0.01). During whole‐body passive heat stress, CRI was lower relative to normothermic baseline in both groups (P&lt;0.01). During subsequent LBNP, CRI was further reduced in young adults during 15 and 30 mmHg (P&lt;0.01). In aged adults, CRI was further reduced at 30 mmHg during heating (P=0.06), but not at 15mmHg (P=0.27). Relative to heat stress, rapid saline infusion did not affect CRI in young (P=0.47) or aged (P=0.99) adults. These results demonstrate that CRI responses at low levels of central hypovolemia (i.e. 15 mmHg ≈ 250 ml) differ between young and aged adults under normothermic and heat stress conditions. Furthermore, CRI is unaffected by rapid saline infusion performed under heat stress conditions in both young and aged adults.Support or Funding InformationFunded by the Department of Defense (W81XWH‐12‐1‐0152). CRI responses in young and aged adults. Normothermic baseline LBNP15 LBNP30 Heat stress LBNP15 LBNP30 Infusion Young 0.88±0.06 0.77±0.11* 0.53±0.17* 0.43±0.27* 0.31±0.20† 0.18±0.13† 0.40±0.18 Aged 0.84±0.20 0.79±0.21 0.67±0.24* 0.45±0.20* 0.40±0.20 0.35±0.23† 0.41±0.15 Values are mean ± SD. different from baseline at P≤0.05; different from heat stress at P≤0.06.

Hemodynamic responses to cooling and warming during a continuous simulated hemorrhage ramp

One in 10 deaths worldwide is caused by traumatic injury, and 30–40% of those trauma‐related deaths are due to hemorrhage. Currently, warming a hemorrhaging victim is the standard of care due to the adverse effects of combined hemorrhage and hypothermia on survival. However, heating can be detrimental to the maintenance of arterial pressure and cerebral perfusion during a continuous hypotensive challenge.PURPOSETo test the hypothesis that warming a normothermic individual during a continuous simulated hemorrhage ramp is harmful to the maintenance of arterial pressure and cerebral perfusion, while skin surface cooling is beneficial.METHODSTwelve men (mean ± SD: age, 29 ± 8 y; weight, 82 ± 16 kg) underwent a randomized crossover study performed over 3 separate days. Following 15 min of supine rest, 10 min of 30 mmHg of lower body negative pressure (LBNP) was applied to simulate a mild hemorrhagic challenge. With LBNP continuing, subjects were then exposed to mild whole‐body warming (WARM; mean skin temperature (Tsk): 36.4 ± 0.5°C), skin surface cooling (COOL; Tsk: 30.5 ± 0.9°C), or remained thermoneutral (NEUT; Tsk: 33.9 ± 0.6°C). Five min after the thermal provocation, a continuous LBNP ramp was applied at a rate of 5 mmHg·min−1 until pre‐syncope. Hemodynamic and thermal variables were measured continuously.RESULTSNeither average time to pre‐syncope (P = 0.14) nor the LBNP level at pre‐syncope (P = 0.09) were different between thermal conditions. However, mean arterial blood pressure was elevated (92 ± 11 mmHg; P = 0.01) during COOL across the LBNP period, relative to NEUT (83 ± 9 mmHg) and WARM (79 ± 11 mmHg) trials. Middle cerebral artery blood velocity decreased (26 ± 1 cm·sec−1; P &lt; 0.001) to a similar extent from baseline to pre‐syncope, regardless of the thermal conditions applied.CONCLUSIONSContrary to our hypothesis, WARM did not impair LBNP tolerance or cerebral blood flow velocity. Although COOL increased blood pressure during the LBNP ramp, LBNP tolerance and cerebral perfusion were not different relative to the NEUT or WARM trials. These data indicate that mild whole‐body warming of a continuously hemorrhaging victim is not detrimental to hemodynamic stability.Support or Funding InformationProject funded by DOD‐W81XWH‐12‐1‐0152.

Normothermic central hypovolemia tolerance reflects hyperthermic tolerance

To test the hypothesis that those who are highly tolerant to lower body negative pressure (LBNP) while normothermic are also highly tolerant to this challenge while hyperthermic. Sixty pairs of normothermic and hyperthermic LBNP tests to pre-syncope were evaluated. LBNP tolerance was quantified via the cumulative stress index (CSI), which is calculated as the sum of the product of the LBNP level and the duration of each level until test termination (i.e., 20mmHg×3min+30mmHg×3min, etc.). CSI was compared between normothermic and hyperthermic trials. Internal and skin temperatures, heart rate, and arterial pressure were measured throughout. Hyperthermia reduced (P<0.001) CSI from 997±437 to 303±213mmHgmin. There was a positive correlation between normothermic and hyperthermic LBNP tolerance (R (2)=0.38; P<0.001). As a secondary analysis, the 20 trials with the highest LBNP tolerance while normothermic were identified (indicated as the HIGH group; CSI 1,467±356mmHgmin), as were the 20 trials with the lowest normothermic tolerance (indicated as the LOW group; CSI 565±166mmHgmin; P<0.001 between groups). While hyperthermia unanimously reduced CSI in both HIGH and LOW groups, in this hyperthermic condition CSI was ~threefold higher in the HIGH group (474±226mmHgmin) relative to the LOW group (160±115mmHgmin; P<0.001). LBNP tolerance while hyperthermic is related to normothermic tolerance and, associated with this finding, those who have a high LBNP tolerance while normothermic remain relatively tolerant when hyperthermic.

Copeptin and norepinephrine during graded hypovolemic stress in women prone to vasovagal syncope (858.6)

Objective: Vasovagal syncope is the most common form of syncope in young individuals, with increased incidence in women. Despite being common, the aetiology is not elucidated. The aim was to study various biomarkers involved in blood pressure homeostasis in women prone to vasovagal syncope.Design and Methods: Graded lower body negative pressure (LBNP) to presyncope was used determine LBNP tolerance index (LTI) in 13 young women prone to vasovagal syncope (VVS) and 15 matched controls (C). Plasma levels of Norepinephrine (P‐NE), Copeptin, a surrogate marker of vasopressin (Cop) and midregion proadenomedullin (MR‐ProADM) was measured before and during graded LBNP.Results: LTI was lower in VVS (163±8) compared to controls (235±8) (P &lt; 0.0001). VVS presented with increased levels of P‐NE at rest as well as LBNP of 30 mmHg, with similar levels at presyncope. P‐NE increase from rest to presyncope was smaller in VVS than in C (P = 0.01). Cop was greater in VVS during LBNP of 30 mmHg, but similar during presyncope. MR‐ProADM was unaffected by graded hypovolemia.Conclusions: Women prone to VVS present with increased levels of P‐NE and Cop during early LBNP, but with similar levels at presyncope, possibly as a result of greater hypovolemic stress at a given LBNP level. To elucidate its role in VVS, these data must be interpreted together with other data during hypovolemia.

Are you bleeding? Validation of a machine-learning algorithm for determination of blood volume status: application to remote triage

Due to limited remote triage monitoring capabilities, combat medics cannot currently distinguish bleeding soldiers from those engaged in combat unless they have physical access to them. The purpose of this study was to test the hypothesis that low-level physiological signals can be used to develop a machine-learning algorithm for tracking changes in central blood volume that will subsequently distinguish central hypovolemia from physical activity. Twenty-four subjects underwent central hypovolemia via lower body negative pressure (LBNP), and a supine-cycle exercise protocol. Exercise workloads were determined by matching heart rate responses from each LBNP level. Heart rate and stroke volume (SV) were measured via Finometer. ECG, heat flux, skin temperature, galvanic skin response, and two-axis acceleration were obtained from an armband (SenseWear Pro2) and used to develop a machine-learning algorithm to predict changes in SV as an index of central blood volume under both conditions. The algorithm SV was retrospectively compared against Finometer SV. A model was developed to determine whether unknown data points could be correctly classified into these two conditions using leave-one-out cross-validation. Algorithm vs. Finometer SV values were strongly correlated for LBNP in individual subjects (mean r = 0.92; range 0.75-0.98), but only moderately correlated for exercise (mean r = 0.50; range -0.23-0.87). From the first level of LBNP/exercise, the machine-learning algorithm was able to distinguish between LBNP and exercise with high accuracy, sensitivity, and specificity (all ≥90%). In conclusion, a machine-learning algorithm developed from low-level physiological signals could reliably distinguish central hypovolemia from exercise, indicating that this device could provide battlefield remote triage capabilities.

Left ventricular longitudinal strain and strain rate are preload dependent

2D‐speckle tracking echocardiography (STE) derived strain and strain rate measurements have been proposed as potential non‐invasive measures of myocardial deformation and function. However, the effects of left ventricular (LV) loading conditions on 2D‐STE derived LV longitudinal strain and strain rate have not been elucidated. The aim of this study was to determine whether acute preload reduction by Lower Body Negative Pressure (LBNP) would alter 2D‐STE derived LV longitudinal strain and strain rate. LBNP varied between 0, −10, −20, −30, −40 and −50 mmHg (3 min/level) as strain and strain rate were assessed in 12 healthy individuals (26±1 yrs, 6 females and 6 males). Systolic peak strain (%), systolic (S‐Sr), early and late diastolic strain rate (E‐Sr and A‐Sr) were measured from standard LV apical views at each LBNP level. Compared to baseline, LBNP caused significant decreases in LV end‐diastolic volume (P&lt;0.05) and stroke volume (P&lt;0.01) while heart rate increased (P&lt;0.01). LV longitudinal strain and strain rate decreased at LBNP ≥ −40 mmHg. Our results indicate that 2D STE‐derived longitudinal strain and strain rate are sensitive to acute preload changes. Thus, the effects of preload should be considered when strain and strain rate are used as indices of systolic and diastolic function.Supported by P01 HL096570 (LIS); UL1 RR033184 (LIS).

Use of Advanced Machine-Learning Techniques for Noninvasive Monitoring of Hemorrhage

Hemorrhagic shock is a leading cause of death in both civilian and battlefield trauma. Currently available medical monitors provide measures of standard vital signs that are insensitive and nonspecific. More important, hypotension and other signs and symptoms of shock can appear when it may be too late to apply effective life-saving interventions. The resulting challenge is that early diagnosis is difficult because hemorrhagic shock is first recognized by late-responding vital signs and symptoms. The purpose of these experiments was to test the hypothesis that state-of-the-art machine-learning techniques, when integrated with novel non-invasive monitoring technologies, could detect early indicators of blood volume loss and impending circulatory failure in conscious, healthy humans who experience reduced central blood volume. Humans were exposed to progressive reductions in central blood volume using lower body negative pressure as a model of hemorrhage until the onset of hemodynamic decompensation. Continuous, noninvasively measured hemodynamic signals were used for the development of machine-learning algorithms. Accuracy estimates were obtained by building models using signals from all but one subject and testing on that subject. This process was repeated, each time using a different subject. The model was 96.5% accurate in predicting the estimated amount of reduced central blood volume, and the correlation between predicted and actual lower body negative pressure level for hemodynamic decompensation was 0.89. Machine modeling can accurately identify reduced central blood volume and predict impending hemodynamic decompensation (shock onset) in individuals. Such a capability can provide decision support for earlier intervention.

Tissue Doppler of Early Mitral Filling Correlates With Simulated Volume Loss in Healthy Subjects

The accurate noninvasive assessment of preload in emergency department (ED) patients remains elusive. Point-of-care ultrasound (US) imaging, particularly evaluation of the inferior vena cava (IVC), has been shown to be qualitatively helpful. Doppler and tissue Doppler are now routinely available on ED US equipment, but few studies have looked at the correlation of dynamic changes in these parameters in a controlled model of hypovolemia. Our objective was to examine the correlation of Doppler parameters to simulated volume loss in healthy subjects using a lower-body negative pressure (LBNP) model and to compare these measurements to commonly used IVC measurements of preload. Twelve paid volunteers with no known cardiovascular disease between the ages of 23 and 31 years old (mean ± SD = 25.5 ± 2.5 years old) were recruited. Hypovolemia was simulated using graduated LBNP levels with measurements taken at 0, -30, and -60 mm Hg and lower pressures as tolerated. Vital signs were monitored in all patients. US measurements recorded at each negative pressure level included IVC maximum (IVC(max)) and minimum (IVC(min)) dimensions; early (E) and late (A) transmitral filling velocities using pulsed-wave spectral Doppler; and early (E') and late (A') tissue Doppler velocities at the septal ((sep)) and lateral ((lat)) mitral annulus, using pulsed-wave tissue Doppler. Lower-body negative pressure correlated significantly and positively within subjects for all US parameters except for the A filling wave. E'(lat) and E'(sep) showed the strongest correlation with R² values of 0.749 (95% confidence interval [CI] = 0.577 to 0.854) and 0.738 (95% CI = 0.579 to 0.875) respectively, followed by A'(sep) 0.674 (95% CI = 0.416 to 0.845), IVC(max) 0.638 (95% CI = 0.425 to 0.806), A'(lat) 0.547 (95% CI = 0.280 to 0.802), IVC(min) 0.512 (95% CI = 0.192 to 0.777), and E 0.478 (95% CI = 0.187 to 0.762). Ratios correlated only moderately with LBNP level, including E/ E'(lat) R² of 0.430 (95% CI = 0.131 to 0.706), E/ E'(sep) 0.416 (95% CI = 0.183 to 0.686), and IVC collapsibility index (IVC(CI)) 0.201 (95% CI = 0.003 to 0.681). Vital signs, including heart rate and blood pressure, did not vary significantly with LBNP levels. In this pilot study of healthy subjects, tissue Doppler assessment of early diastolic filling correlated most strongly with simulated hypovolemia.

TRACKING CENTRAL HYPOVOLEMIA WITH ECG IN HUMANS

Heart period variability (HPV) metrics have been suggested for use in medical monitoring of trauma patients. This study sought to ascertain the use of various HPV metrics in tracking central blood volume during simulated hemorrhage in individual humans. One hundred one healthy nonsmoking volunteers (58 men, 43 women) were instrumented for continuous measurement of electrocardiogram and beat-by-beat finger arterial blood pressure. Stroke volume (SV) was estimated from the arterial pulse wave and used to reflect central blood volume. Progressive lower body negative pressure (LBNP) was applied in 5-min stages until the onset of impending hemodynamic decompensation (systolic blood pressure <70 mmHg and/or presyncopal symptoms). HPV was assessed with analysis of R-to-R intervals using both linear (time and frequency domains) and nonlinear (e.g., complexity, fractality) methods. Application of increasing LBNP caused progressive reductions of SV, whereas arterial pressures changed only minimally and late. Group LBNP stage means for each HPV metric changed progressively and were strongly correlated with the mean decrease in SV (|r| > or = 0.87). To ascertain the utility of the HPV metrics to track individual responses to central hypovolemia, the difference scores for each HPV metric were correlated at each successive LBNP level, with percentage change in SV at the subject level. This cross-correlation of difference scores revealed that none of the HPV metrics showed strong and consistent correlations (|r| < or = 0.49) with percentage change in SV across successive LBNP levels. Although aggregate group mean values for HPV metrics are well correlated with SV changes during central hypovolemia, these metrics are less reliable when tracking individual reductions in central volume during LBNP. HPV metrics, therefore, may not be useful in monitoring hemorrhagic injuries in individual patients.

Bleeding Or Active? Validation Of A Machine-learning Algorithm For Remote Determination Of Blood Volume Status

Due to the lack of remote monitoring capabilities, combat medics cannot currently distinguish a wounded and bleeding soldier from a soldier who is engaged in combat unless they have physical access to them. We have previously shown that traditionally measured vital signs may not provide the specificity required to distinguish between a bleeding or physically active soldier, but a measure of volume status (e.g., pulse pressure (PP)), may be able to achieve this purpose. PURPOSE: To assess whether a machine-learning algorithm programmed within a wearable, non-invasive armband can track changes in PP and therefore distinguish between the conditions of central hypovolemia and exercise. METHODS: Twenty five human subjects underwent progressive central hypovolemia via lower body negative pressure (LBNP); 8 of these subjects also participated in a supine cycle exercise protocol (≥5 weeks later). Exercise workloads were determined by matching heart rate (HR) responses at each LBNP level. HR (via ECG) and arterial blood pressure (via Finometer®) were measured continuously. Subjects wore a SenseWear® Pro2 Armband that measured heat flux, HR, skin temperature, galvanic skin response, and 3-axis acceleration. These measurements were used to develop a machine-learning algorithm to predict changes in PP as an index of central blood volume under both conditions; these predictions were retrospectively compared against actual PP values obtained from the Finometer®. An additional model was created to determine if the accuracy, sensitivity, and specificity of unknown data points could be correctly classified into these two conditions (N = 8). RESULTS: Predicted versus actual PP values were highly correlated for both LBNP (r = 0.84; n = 25) and exercise (r = 0.86; n = 8). The machine learning algorithm was able to distinguish between LBNP and exercise with high accuracy (94%), sensitivity (95%), and specificity (92%). CONCLUSIONS: These results demonstrate that a wearable armband with a machine-learning algorithm was able to reliably track changes in PP during both central hypovolemia and exercise. This device could provide remote triage capabilities for future battlefield use.

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.

Validation of a computational platform for the analysis of the physiologic mechanisms of a human experimental model of hemorrhage

Computational models of integrative physiology may serve as a framework for understanding the complex adaptive responses essential for homeostasis in critical illness and resuscitation and may provide insights for design of diagnostics and therapeutics. In this study a computer model of human physiology was compared to results obtained from experiments using Lower Body Negative Pressure (LBNP) analog model of human hemorrhage. LBNP has been demonstrated to produce physiologic changes in humans consistent with hemorrhage. The computer model contains over 4000 parameters that describe the detailed integration of physiology based upon basic physical principles and established biologic interactions. The LBNP protocol consisted of a 5 min rest period (0 mmHg) followed by 5 min of chamber decompression of the lower body to −15, −30, −45, and −60 mmHg and additional increments of −10 mmHg every 5 min until the onset of hemodynamic decompensation ( n = 20). Physiologic parameters recorded include mean arterial pressure (MAP), cardiac output (CO), and venous oxygen saturation (SVO 2; from peripheral venous blood), during the last 30 s at each LBNP level. The computer model analytic procedure recreates the investigational protocol for a virtual individual in an In Silico environment. After baseline normalization, the model predicted measurements for MAP, CO, and SVO 2 were compared to those observed through the entire range of LBNP. Differences were evaluated using standard statistical performance error measurements (median performance error (PE) <5%). The simulation results closely tracked the average changes observed during LBNP. The predicted MAP fell outside the standard error measurement for the experimental data at only LBNP −30 mmHg while CO was more variable. The predicted SVO 2 fell outside the standard error measurement for the experimental data only during the post-LBNP recovery point. However, the statistical median PE measurement was found to be within the 5% objective error measure (1.3% for MAP, −3.5% for CO, and 3.95% for SVO 2). The computer model was found to accurately predict the experimental results observed using LBNP. The model should be explored as a platform for studying concepts and physiologic mechanisms of hemorrhage including its diagnosis and treatment.

Combat Stress or Hemorrhage? Evidence for a Decision-Assist Algorithm for Remote Triage

In the setting of remote military triage, when physical access to the patient is not possible, traditional physiological measurements available to a combat medic may not differentiate between a wounded soldier and an active soldier. We tested the hypothesis that changes in high-frequency R-R interval spectral power (RRI HF) and pulse pressure (PP) would differ between progressive central hypovolemia (simulated hemorrhage) and exercise to evaluate their potential for remotely distinguishing active from bleeding soldiers. The RRI HF and PP were used because of their ability to track central hypovolemia. There were 12 (8 female/4 male) healthy, normotensive, nonsmoking subjects (age 27 +/- 2 yr; height 169 +/- 3 cm; weight 68 +/- 5 kg) who were exposed to progressive lower body negative pressure (LBNP) and a supine cycle ergometer protocol. ECG and blood pressure were measured continuously. Exercise workloads were determined by matching the heart rate (HR) responses to each LBNP level. Data were analyzed in time and frequency domains. HR increased from 67 +/- 3 bpm at rest to 101 +/- 4 bpm by -60 mmHg LBNP and was matched within 5% during exercise. By the final stage, RRI HF decreased by a similar magnitude during both LBNP (-78 +/- 7%) and exercise (-85 +/- 6%). PP decreased by 30 +/- 4% with LBNP compared with an increase of 20 +/- 6% during exercise. Monitoring PP in combination with RRI HF would distinguish a bleeding from an active soldier. Technologies that incorporate telemetry to track these derived vital signs would provide a combat medic with remote decision support to assess soldier status on the battlefield.

Human muscle sympathetic action potential patterns during graded lower body negative pressure

This study assessed baroreflex modulation of within‐burst neural action potential (spike) discharge in muscle sympathetic nerve activity (MSNA). Spike rate and inter‐spike interval were exposed from raw MSNA recorded from 6 healthy individuals during graded lower body negative pressure (LBNP) (baseline, −10, −40, −60 mmHg). The first 30s raw MSNA of the 4th min for each LBNP level was analyzed after applying a spike detection method (Autonomic neuroscience: Basic &amp; Clinical 143(2007) 92–105). Spikes/30 sec increased progressively with LBNP beginning at −10 mmHg (P&lt;0.05), with a doubling of spike rate (range = 40 – 290%) at −60 mmHg. Mean inter‐spike interval decreased progressively from 0.175±0.045 s at Baseline to 0.087±0.028 s at −60 LBNP (P&lt;0.05) reflecting increases in average discharge frequencies from 5 to 10 Hz. In probability distributions, progressive increases in the proportion of spikes occurred only within the shortest inter‐spike interval bin (ranging 0.04 (25 Hz) – 0.1 (10 Hz) s across participants). Thus, the increment in MSNA with baroreceptor unloading is focused at high‐frequency discharge patterns and reflects progressive increments in action potential content with evidence for a doubling of neurons recruited between baseline and high levels of orthostatic stress.Supported by NSERC‐CHRP

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.

Effects of Lower Body Negative Pressure on Cardiac and Vascular Responses to Carotid Baroreflex Stimulation.

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29±4 years) we applied sinusoidal neck suction (0 to –30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to –50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (–10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at –10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.