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Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and "Braslet-M" Occlusion Cuffs

Recent advances in remotely guided imaging techniques on ISS allow the acquisition of high quality ultrasound data using crewmember operators with no medical background and minimal training. However, ongoing efforts are required to develop and validate methodology for complex imaging protocols to ensure their repeatability, efficiency, and suitability for use aboard the ISS. This Station Developmental Test Objective (SDTO) tests a cardiovascular evaluation methodology that takes advantage of the ISS Ultrasound capability, the Braslet-M device, and modified respiratory maneuvers (Valsalva and Mueller), to broaden the spectrum of anatomical and functional information on human cardiovascular system during long-duration space missions. The proposed methodology optimizes and combines new and previously demonstrated methods, and is expected to benefit medically indicated assessments, operational research protocols, and data collections for science. Braslet-M is a current Russian operational countermeasure that compresses the upper thigh to impede the venous return from lower extremities. The goal of the SDTO is to establish and validate a repeatable ultrasound-based methodology for the assessment of a number of cardiovascular criteria in microgravity. Braslet-M device is used as a means to acutely alter volume distribution while focused ultrasound measurements are performed. Modified respiratory maneuvers are done upon volume manipulations to record commensurate changes in anatomical and functional parameters. The overall cardiovascular effects of the Braslet-M device are not completely understood, and although not a primary objective of this SDTO, this effort will provide pilot data regarding the suitability of Braslet-M for its intended purpose, effects, and the indications for its use.

Bogomolov, V. V.↗

Exploring Heart and Lung Function in Space: ARMS Experiments

The Advanced Respiratory Monitoring System (ARMS) is a suite of monitoring instruments and supplies used to study the heart, lungs, and metabolism. Many experiments sponsored by the European Space Agency (ESA) will be conducted using ARMS during STS-107. The near-weightless environment of space causes the body to undergo many physiological adaptations, and the regulation of blood pressure is no exception. Astronauts also experience a decrease in blood volume as an adaptation to microgravity. Reduced blood volume may not provide enough blood pressure to the head during entry or landing. As a result, astronauts often experience light-headedness, and sometimes even fainting, when they stand shortly after returning to Earth. To help regulate blood pressure and heart rate, baroreceptors, sensors located in artery walls in the neck and near the heart, control blood pressure by sending information to the brain and ensuring blood flow to organs. These mechanisms work properly in Earth's gravity but must adapt in the microgravity environment of space. However, upon return to Earth during entry and landing, the cardiovascular system must readjust itself to gravity, which can cause fluctuation in the control of blood pressure and heart rate. Although the system recovers in hours or days, these occurrences are not easily predicted or understood - a puzzle investigators will study with the ARMS equipment. In space, researchers can focus on aspects of the cardiovascular system normally masked by gravity. The STS-107 experiments using ARMS will provide data on how the heart and lungs function in space, as well as how the nervous system controls them. Exercise will also be combined with breath holding and straining (the Valsalva maneuver) to test how heart rate and blood pressure react to different stresses. This understanding will improve astronauts' cardiopulmonary function after return to Earth, and may well help Earthbound patients who experience similar effects after long-term bed rest.

Andre Kuipers↗

Anatomical and functional characteristics of carotid sinus stimulation in humans

Transmission characteristics of pneumatic pressure to the carotid sinus were evaluated in 19 subjects at rest and during exercise. Either a percutaneous fluid-filled (n = 12) or balloon-tipped catheter (n = 7) was placed at the carotid bifurcation to record internal transmission of external neck pressure/neck suction (NP/NS). Sustained, 5-s pulses, and rapid ramping pulse protocols (+40 to -80 Torr) were recorded. Transmission of pressure stimuli was less with the fluid-filled catheter compared with that of the balloon-tipped catheter (65% vs. 82% negative pressure, 83% vs. 89% positive pressure; P < 0.05). Anatomical location of the carotid sinus averaged 3.2 cm (left) and 3.6 cm (right) from the gonion of the mandible with a range of 0-7.5 cm. Transmission was not altered by exercise or Valsalva maneuver, but did vary depending on the position of the carotid sinus locus beneath the sealed chamber. These data indicate that transmission of external NP/NS was higher than previously recorded in humans, and anatomical variation of carotid sinus location and equipment design can affect transmission results.

Randomized Controlled Trial↗

Cerebrovascular regulation in the postural orthostatic tachycardia syndrome (POTS)

Patients with the postural orthostatic tachycardia syndrome (POTS) have symptoms of orthostatic intolerance despite having a normal orthostatic blood pressure (BP), which suggests some impairment of cerebrovascular regulation. Cerebrovascular autoregulation refers to the maintenance of normal cerebral blood flow in spite of changing BP. Mechanisms of autoregulation include myogenic, metabolic and neurogenic vasoregulation. Beat-to-beat recording of blood-flow velocity (BFV) is possible using transcranial Doppler imaging. It is possible to evaluate autoregulation by regressing deltaBFV to deltaBP during head-up tilt. A number of dynamic methods, relating deltaBFV to deltaBP during sudden induced changes in BP by occluding then releasing peripheral arterial flow or by the Valsalva maneuver. The deltaBFV to deltaBP provides an index of autoregulation. In orthostatic hypotension, the autoregulated range is typically expanded. In contrast, paradoxical vasoconstriction occurs in POTS because of an increased depth of respiration, resulting in hypocapnic cerebrovascular constriction, and impaired autoregulation.

Review↗

The Incidence of Patent Foramen Ovale in 1,000 Consecutive Patients: A Contrast Transesophageal Echocardiography Study

Study objective: Patent foramen ovale (PFO) is present in 10 to 35% of people and has been reported to be an important risk factor for cardioembolic cerebrovascular accidents (CVAs) and transient ischemic attacks (TIAS), especially in younger patients. While contrast transthoracic echocardiography has been used to detect PFO, contrast transesophageal echocardiography (TEE) has a greater sensitivity. Prior studies reported the incidence of PFO in patients presenting with a CVA or TIA. Design: To determine the incidence of PFO in a more general population, we reviewed 1,000 consecutive TEES performed with contrast and color Doppler for the presence of PFO and other cardioembolic risk factors, including atrial septal aneurysm (ASA), aortic plaque, atrial fibrillation (AFib), and atrial thrombi. While imaging with monoplane or biplane TEE, multiple injections of agitated saline solution were injected during cough or Valsalva maneuver to detect flow through a PFO. Patients: There were 482 male and 518 female patients with mean age of 60 + 17 years (range 11 to 93 years). Results: Patent foramen ovale was found in 9.2% of all patients and, though seen in all age groups divided by decade, the incidence in patients aged 40 to 49 years was greater than those aged 70 to 79 years (12.96% vs 6.15%',, p=0.03). Contrast TEE had a much higher detection rate than color Doppler alone. Importantly, there was no greater incidence of PFO in patients with CVA vs thos~ without CVA, or in male vs female patients. Also, there was a very strong correlation between the presence of ASA and PFO (p<.001). Conclusion: Thus, PFO detected by TEE, frequently seen with ASA, is seen in all age groups and does not in itself present a risk factor for CVA. The association of PFO with peripheral thrombosis and CVA needs further study.

Fisher, Daniel C.↗

Transesophageal Echocardiography and Contrast-TCD in the Detection of a Patent Foramen Ovale: Experience with 111 Patients

Patent foramen ovale (PFO) is increasingly recognized in association with cryptogenic stroke. Using transesophageal echocardiography (TEE) and transcranial Doppler sonography with ultrasonic contrast medium contrast-(TCD), we evaluated the frequency of a PFO as the fundamental condition of paradoxical embolism in 111 patients after cerebral ischemia. There was a right-left shunt in 50 patients (45%) with TEE. In 31 of 40 patients with stroke of unknown etiology, a PFO was the only detectable finding associated with cerebral ischemia. Using TEE as he "gold standard," the sensitivity of contrast-TCD was 91.3%, specificity 93.8%, and the overall accuracy 92.8%. contrast-TCD failed to detect a right-left shunt in four patients, but there were four other patients with negative TEE and positive contrast-TCD. We conclude that contrast-TCD is a highly sensitive method for detecting a right-left shunt. Its advantages are low cost, its ability to detect single contrast-medium embolism, and control of the Valsalva maneuver by observing the decrease of cerebral blood flow. Evidence of PFO in cryptogenic stroke should prompt a search for a subclinical venous thrombosis as the embolic source.

Klotzsch, Christof↗

In-suit CO2 Washout Test System (ICWTS) for CO2 Washout Verification in Spacesuits

Since the time of Mercury, Gemini, and Apollo, NASA has been performing CO 2 washout verification of spacesuits with Human in the Loop (HITL) test methods. Classically, the only instrumentation both with the accuracy and response time necessary was that of external mass spectrometers or medical gas analyzers fed by a long capillary line from the oro-nasal region within the suit. The helmet CO 2 washout configuration including the challenges posed by variation of a suited human subject frequently created difficulty in capturing adequate breath by breath data. For example, a nasal cannula could be worn with reasonable comfort however it posed the following challenges: (1) impeded the test subject’s ability to do a proper Valsalva maneuver; (2) frequently provided a corrupted waveform with relative movement; (3) precluded the ability to evaluate the Flow Weighted Average (FWA) at subject interface. A mouthpiece could be used in lieu of a cannula but posed challenges as well: (1) created potential disturbances of the flow field; (2) precluded the test subject from speaking during usage; and (3) presented comfort issues limiting the duration of test points. These challenges made it impractical to use a mouthpiece for anything other than short lab ambient environment tests. Technology development and NASA investment have afforded new capabilities to address some of these measurements providing improved data collection and are implemented in the In-suit CO 2 Washout Test System (ICWTS) which provides suit inlet/outlet pressure, temperature, relative humidity, partial pressure of oxygen, partial pressure of CO 2 , and flow measurement coupled with the acquisition of the inspired PPCO 2 including the ability for FWA measurement. This test system, coupled with use of the In-suit Respiration Mannequin Assembly (IRMA) and Computational Fluid Dynamics (CFD) combine to provide a full picture of the in-suit oro-nasal flow field and effectiveness of CO 2 washout in a spacesuit design.

Colin Campbell↗

In-suit CO 2 Washout Test System (ICWTS) for CO 2 Washout Verification in Spacesuits

Since the time of Mercury, Gemini, and Apollo, NASA has been performing CO 2 washout verification of spacesuits with Human in the Loop (HITL) test methods. Classically, the only instrumentation both with the accuracy and response time necessary was that of external mass spectrometers or medical gas analyzers fed by a long capillary line from the oro-nasal region within the suit. The helmet CO 2 washout configuration including the challenges posed by variation of a suited human subject frequently created difficulty in capturing adequate breath by breath data. For example, a nasal cannula could be worn with reasonable comfort however it posed the following challenges: (1) impeded the test subject’s ability to do a proper Valsalva maneuver; (2) frequently provided a corrupted waveform with relative movement; (3) precluded the ability to evaluate the Flow Weighted Average (FWA) at subject interface. A mouthpiece could be used in lieu of a cannula but posed challenges as well: (1) created potential disturbances of the flow field; (2) precluded the test subject from speaking during usage; and (3) presented comfort issues limiting the duration of test points. These challenges made it impractical to use a mouthpiece for anything other than short lab ambient environment tests. Technology development and NASA investment have afforded new capabilities to address some of these measurements providing improved data collection and are implemented in the In-suit CO 2 Washout Test System (ICWTS) which provides suit inlet/outlet pressure, temperature, relative humidity, partial pressure of oxygen, partial pressure of CO 2 , and flow measurement coupled with the acquisition of the inspired PPCO 2 including the ability for FWA measurement. This test system, coupled with use of the In-suit Respiration Mannequin Assembly (IRMA) and Computational Fluid Dynamics (CFD) combine to provide a full picture of the in-suit oro-nasal flow field and effectiveness of CO 2 washout in a spacesuit design.

Colin Campbell↗

The autonomic laboratory

The autonomic nervous system can now be studied quantitatively, noninvasively, and reproducibly in a clinical autonomic laboratory. The approach at the Mayo Clinic is to study the postganglionic sympathetic nerve fibers of peripheral nerve (using the quantitative sudomotor axon reflex test [QSART]), the parasympathetic nerves to the heart (cardiovagal tests), and the regulation of blood pressure by the baroreflexes (adrenergic tests). Patient preparation is extremely important, since the state of the patient influences the results of autonomic function tests. The autonomic technologist in this evolving field needs to have a solid core of knowledge of autonomic physiology and autonomic function tests, followed by training in the performance of these tests in a standardized fashion. The range and utilization of tests of autonomic function will likely continue to evolve.

NASA Discipline Cardiopulmonary↗

Orthostatic intolerance and motion sickness after parabolic flight

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

NASA Center JSC↗

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using Ultrasound and Braslet-M Occlusion Cuffs

The objective of this joint U.S. - Russian project was the development and validation of an in-flight methodology to assess a number of cardiac and vascular parameters associated with circulating volume and its manipulation in long-duration space flight. Responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound (US) before, during, and after temporary volume reduction by means of Braslet-M thigh occlusion cuffs (Russia). Materials and Methods: The study protocol was conducted in 14 sessions on 9 ISS crewmembers, with an average exposure to microgravity of 122 days. Baseline cardiovascular measurements were taken by echocardiography in multiple modes (including tissue Doppler of both ventricles) and femoral and jugular vein imaging on the International Space Station (ISS). The Braslet devices were then applied and measurements were repeated after >10 minutes. The cuffs were then released and the hemodynamic recovery process was monitored. Modified Valsalva and Mueller maneuvers were used throughout the protocol. All US data were acquired by the HDI-5000 ultrasound system aboard the ISS (ATL/Philips, USA) during remotely guided sessions. The study protocol, including the use of Braslet-M for this purpose, was approved by the ISS Human Research Multilateral Review Board (HRMRB). Results: The effects of fluid sequestration on a number of echocardiographic and vascular parameters were readily detectable by in-flight US, as were responses to respiratory maneuvers. The overall volume status assessment methodology appears to be valid and practical, with a decrease in left heart lateral E (tissue Doppler) as one of the most reliable measures. Increase in the femoral vein cross-sectional areas was consistently observed with Braslet application. Other significant differences and trends within the extensive cardiovascular data were also observed. (Decreased - RV and LV preload indices, Cardiac Output, LV E all maneuvers, LV Stroke Volume). Conclusions: This Study: 1) Addressed specific aspects of operational space medicine and space physiology, including assessment of circulating volume disturbances 2) Expanded the applications of diagnostic ultrasound imaging and Doppler techniques in microgravity. 3) Used respiratory maneuvers against the background of acute circulating volume manipulations which appear to enhance our ability to noninvasively detect volume-dependency in a number of cardiac and vascular parameters. 4) Determined that Tei index is not clinically changed therefore contractility not altered in the face of reduced preload. 5) Determined that increased Femoral Vein Area indicating blood being sequestered in lower extremities correlates with reduced preload and cardiac output. 6) That Braslet may be the only feasible means of acutely treating high pressure pulmonary edema in reduced gravity environments.

Hamilton, Douglas↗

Cardiac and Vascular Responses to Thigh Cuffs and Respiratory Maneuvers on Crewmembers of the International Space Station

The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, and a decrease in leg diameter. This experiment examined the responses to modified Valsalva and Mueller maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady state and during preload reduction introduced with thigh occlusion cuffs used as a counter-measure device (Braslet cuffs) measured by cardiac and vascular ultrasound examinations. Methods: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 +/- 46.days after launch (mean +/- SD; 33 - 185). Twenty Seven cardiac and vascular parameters were obtained with/without respiratory maneuvers before and after tightening of the Braslet cuffs. Results: Non-physicians performed diagnostic-quality cardiac and vascular ultrasound examinations using remote guidance. Three of 27 combinations of maneuvers and Braslet or Braslet alone were identified as being significant changed when compared to baseline. Eleven of 81 differences between combinations of Mueller, Valsalva or baseline were significant and related to cardiac preload reduction or increase in lower extremity venous volume. Conclusions: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts commensurate measurable effects on cardiac performance in microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an invaluable tool in determining the volume status of the cardiac patient at the 'microgravity bedside'.

Hamilton, Douglas↗

Acute Modifications of Circulating Volume and Respiratory Maneuvers in the Cardiovascular Assessment of Long-Duration Crewmembers

This U.S. - Russian project is aimed at improved assessment of cardiac and vascular parameters associated with circulating volume and its distribution in long-duration space flight. Objective responses to modified Valsalva and Mueller maneuvers were measured by cardiac and vascular ultrasound before, during, and after temporary volume redistribution by means of Braslet-M thigh occlusion cuffs (Russia). Braslet-M cuffs are custom fitted to each crewmember prior to launch on the Soyuz as a Russian countermeasure for space adaptation fluid shifts

Bogomolov, V. V.↗

Validation of On-Orbit Methodology for the Assessment of Cardiac Function and Changes in the Circulating Volume Using "Braslet-M" Occlusion Cuffs

BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients in the vascular system. The resulting fluid redistribution commonly manifests as facial edema, engorgement of the external neck veins, nasal congestion, and headache. This experiment examined the responses to modified Valsalva and Mueller maneuvers as measured by cardiac and vascular ultrasound in a baseline microgravity steady state, and under the influence of thigh occlusion cuffs (Braslet cuffs). METHODS: Nine International Space Station crewmember subjects (Expeditions 16 - 20) were examined in 15 experiment sessions 101 46 days after launch (mean SD; 33 - 185). 27 cardiac and vascular parameters were obtained under three respiratory conditions (baseline, Valsalva, and Mueller) before and after tightening of the Braslet cuffs for a total of 162 data points per session. The quality of cardiac and vascular ultrasound examinations was assured through remote monitoring and guidance by Investigators from the NASA Telescience Center in Houston, TX, USA. RESULTS: Fourteen of the 81 measured conditions were significantly different with Braslet application and were apparently related to cardiac preload reduction or increase in the venous volume sequestered in the lower extremity. These changes represented 10 of the 27 parameters measured. In secondary analysis, 7 of the 27 parameters were found to respond differently to respiratory maneuvers depending on the presence or absence of thigh compression, with a total of 11 differences. CONCLUSIONS: Acute application of Braslet occlusion cuffs causes lower extremity fluid sequestration and exerts proportionate measurable effects on cardiac performance in microgravity. Ultrasound techniques measuring the hemodynamic effects of thigh cuffs in combination with respiratory maneuvers may serve as an effective tool in determining the volume status of a cardiac or hemodynamically compromised patient in microgravity.

Hamilton, D. R.↗

Right Ventricular Tissue Doppler Assessment in Space During Circulating Volume Modification using the Braslet-M Device

This joint U.S. - Russian work aims to establish a methodology for assessing cardiac function in microgravity in association with manipulation of central circulating volume. Russian Braslet-M occlusion cuffs were used to temporarily increase the volume of blood in the lower extremities, which effectively reduces the volume returning to the heart in the central circulation. A novel methodology was tested on the International Space Station (ISS) to assess the volume status of crewmembers by evaluating the responses to application and release of the Braslet-on-occlusion cuffs, as well as to modified Valsalva and Mueller maneuvers. Baseline echocardiographic tissue Doppler imaging (TDI) of the right ventricular free wall with no Braslet applied shows early diastolic E' (16 cm/sec), late diastolic A' (14 cm/sec), and systolic (12 cm/sec) velocities compatible with normal subjects on Earth. TDI of the RV free wall with Braslet applied shows that early diastolic E' decreased by 50% (8 cm/sec), late diastolic A' increased by 45%, and systolic S' remains unchanged. TDI of the RV free wall approximately 8 beats after the Braslet was released shows early diastolic E' (8 cm/sec), late diastolic A' (12 cm/sec), and systolic S' (13 cm/sec) velocities. During this portion of the release, early diastolic E' did not recover to baseline values but late diastolic A' and systolic S' recovered to pre-Braslet values. The pre-systolic cross-sectional area of the internal jugular vein with Braslet off was 1.07 cm(sup 2) and 1.13 cm(sup 2) 10 min after the Braslet was applied. The presystolic cross-sectional area of the common femoral vein with Braslet off was 0.50 cm(sup 2), and was 0.54 cm(sup 2) 10 min after the Braslet was applied. The right ventricular myocardial performance Tei index also was calculated for comparison with typical values found in healthy subjects on Earth. Baseline and Braslet-on values for Tei index were 0.25 and 0.22 respectively. Braslet Tei indices are within normal ranges found in healthy subjects and temporarily become greater than 0.4 during the dynamic Braslet release portion of this study. Tissue Doppler imaging of the right ventricle revealed that the Braslet influenced cardiac preload and that fluid was sequestered in the lower-extremity interstitial and vascular space after only 10 minutes of application. This report demonstrates that Braslet application affects right ventricular physiology in long-duration space flight based on TDI and that this effect is in part due to venous hemodynamics.

Hamilton, D. R.↗