Use Of Lower Body Negative Pressure Research Articles

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.

Experimental high thoracic spinal cord injury impairs the cardiac and cerebrovascular response to orthostatic challenge in rats.

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats (n = 34) were subjected to a sham or T3-SCI surgery and survived into the chronic period postinjury (i.e., 8 wk). Cardiac function was tracked via ultrasound pre- to post-SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not sham animals. In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared with sham (P < 0.034), whereas heart rate was increased in sham but decreased in SCI (P < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP (P < 0.033), implying impaired dynamic cerebral autoregulation. Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation.NEW & NOTEWORTHY This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.

Lower Body Negative Pressure: Physiological Effects, Applications, and Implementation.

This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249-1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.

Impact of environmental stressors on tolerance to hemorrhage in humans.

Hemorrhage is a leading cause of death in military and civilian settings, and ~85% of potentially survivable battlefield deaths are hemorrhage-related. Soldiers and civilians are exposed to a number of environmental and physiological conditions that have the potential to alter tolerance to a hemorrhagic insult. The objective of this review is to summarize the known impact of commonly encountered environmental and physiological conditions on tolerance to hemorrhagic insult, primarily in humans. The majority of the studies used lower body negative pressure (LBNP) to simulate a hemorrhagic insult, although some studies employed incremental blood withdrawal. This review addresses, first, the use of LBNP as a model of hemorrhage-induced central hypovolemia and, then, the effects of the following conditions on tolerance to LBNP: passive and exercise-induced heat stress with and without hypohydration/dehydration, exposure to hypothermia, and exposure to altitude/hypoxia. An understanding of the effects of these environmental and physiological conditions on responses to a hemorrhagic challenge, including tolerance, can enable development and implementation of targeted strategies and interventions to reduce the impact of such conditions on tolerance to a hemorrhagic insult and, ultimately, improve survival from blood loss injuries.

How to build a lower-body differential pressure chamber integrated on a tilt-table: A pedagogy tool to demonstrate the cardiovagal baroreflex

The cardiovagal baroreflex is an important physiological reflex that is commonly taught in health-related university physiology courses. This reflex is responsible for the rapid maintenance of blood pressure through dynamic changes in heart rate (HR) and vascular resistance. The use of lower-body negative pressure (LBNP) and lower-body positive pressure (LBPP) can manipulate these stretch sensitive baroreceptors. High performance and relatively inexpensive homemade LBNP and LBPP chambers can be easily constructed providing a valuable tool for both research and teaching purposes. There has been previous documentation of how to build a LBNP chamber; however, the information available usually lacks appropriate construction details, and there is currently no literature on how to build a chamber that can accommodate both LBNP and LBPP. In addition, a recently developed novel LBNP/LBPP chamber positioned on a 360° tilt-table provided the unique utility of superimposing both LBNP/LBPP and body position as independent or combined stressors to alter central blood volume. The primary purposes of this manuscript are to (1) provide step-by-step instructions on how to build a tilt-table LBNP/LBPP chamber, and (2) demonstrate the effectiveness of a tilt-table LBNP/LBPP chamber to facilitate undergraduate and graduate learning in the laboratory by effectively demonstrating the cardiovagal baroreflex.

Validation of lower body negative pressure as an experimental model of hemorrhage (859.5)

Lower body negative pressure (LBNP), a model of hemorrhage (Hem), shifts blood volume to the legs and elicits central hypovolemia. This study compared the effects of LBNP to actual Hem. Baboons (n=14) were instrumented to measure pulse pressure (PP), central venous pressure (CVP), and stroke volume (SV). Blood was removed in four steps: 6.25%,12.5%, 18.75%, and 25% of total blood volume. Four weeks after Hem, the same animals were subjected to four levels of LBNP which changed PP and CVP as seen during Hem. Blood sampled at baseline and maximum Hem or LBNP measured blood gases, hematocrit, hemoglobin, plasma renin activity (PRA), vasopressin (AVP), epinephrine (EPI) and norepinephrine (NE). Hemodynamic responses to Hem and LBNP were identical. Hem decreased hematocrit, hemoglobin, and central venous oxygen saturation (ScvO2). In contrast, LBNP increased hematocrit, and hemoglobin, while ScvO2 remained unchanged. Hem caused greater (p蠄0.01) elevations in AVP and NE than LBNP, while PRA and EPI did not differ between studies. Thus, stepwise Hem elicited hemodynamic changes which could be mimicked with distinct levels of LBNP, but loss of red blood cells during Hem may result in greater neurohumoral activation. We conclude that while LBNP does not elicit the same effect on blood cell loss as Hem, LBNP mimics the integrative cardiovascular response to Hem, and validates the use of LBNP as an experimental model of Hem. Grant Funding Source: Supported by US Army MRMC

Validation of lower body negative pressure as an experimental model of hemorrhage

Lower body negative pressure (LBNP), a model of hemorrhage (Hem), shifts blood to the legs and elicits central hypovolemia. This study compared responses to LBNP and actual Hem in sedated baboons. Arterial pressure, pulse pressure (PP), central venous pressure (CVP), heart rate, stroke volume (SV), and +dP/dt were measured. Hem steps were 6.25%, 12.5%, 18.75%, and 25% of total estimated blood volume. Shed blood was returned, and 4 wk after Hem, the same animals were subjected to four LBNP levels which elicited equivalent changes in PP and CVP observed during Hem. Blood gases, hematocrit (Hct), hemoglobin (Hb), plasma renin activity (PRA), vasopressin (AVP), epinephrine (EPI), and norepinephrine (NE) were measured at baseline and maximum Hem or LBNP. LBNP levels matched with 6.25%, 12.5%, 18.75%, and 25% hemorrhage were -22 ± 6, -41 ± 7, -54 ± 10, and -71 ± 7 mmHg, respectively (mean ± SD). Hemodynamic responses to Hem and LBNP were similar. SV decreased linearly such that 25% Hem and matching LBNP caused a 50% reduction in SV. Hem caused a decrease in Hct, Hb, and central venous oxygen saturation (ScvO2). In contrast, LBNP increased Hct and Hb, while ScvO2 remained unchanged. Hem caused greater elevations in AVP and NE than LBNP, while PRA, EPI, and other hematologic indexes did not differ between studies. These results indicate that while LBNP does not elicit the same effect on blood cell loss as Hem, LBNP mimics the integrative cardiovascular response to Hem, and validates the use of LBNP as an experimental model of central hypovolemia associated with Hem.

Hemodynamic response to lower body negative pressure in children: A pilot study

Although head-up tilt and upright standing are common methods used to induce orthostatic stress, lower body negative pressure (LBNP) is another safe and easy technique that induces orthostatic stress independently of gravity. However, the use of LBNP in children has never been investigated. The purpose of this pilot study was to determine whether LBNP was capable of inducing hemodynamic adaptations in pre-pubertal boys. Ten healthy pre-pubertal boys (9 ± 1 years) were recruited and randomly exposed to 3 levels of LBNP (15, 20 and 25 mm Hg). Heart rate, manual and beat-by-beat systolic (SBP), diastolic and mean arterial blood pressure were monitored continuously. Aortic diameter was measured at rest and peak aortic blood velocity was recorded continuously for at least 1 min during each condition. R–R interval (RRI), heart rate, stroke volume (SV), cardiac output ( Q), total peripheral resistance (TPR), low frequency (LF) and high frequency (HF) baroreceptor sensitivity (BRS), as well as LF/HF RRI ratio were calculated. With increasing LBNP TPR increased while SBP decreased ( P ≤ 0.05). As well, a trend towards a decrease in SV ( P = 0.054) and Q ( P = 0.06) was found. However, LF and HF BRS, and LF/HF RRI ratio did not significantly change from baseline to LBNP 15, 20 or 25 mm Hg. In conclusion, the results of this pilot study suggest that low levels of LBNP are capable of inducing hemodynamic adaptations in children that are to be expected when undergoing an orthostatic stress. As well, LBNP is a safe and effective method of inducing orthostatic stress in children.

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.