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At least 217 records · Page 12

Storing Blood Cells

The National Cancer Institute worked with Goddard Space Flight Center to propose a solution to the blood-cell freezing problem. White blood cells and bone marrow are stored for future use by leukemia patients as a result of Goddard and Jet Propulsion Laboratory expertise in electronics and cryogenics. White blood cell and bone marrow bank established using freezing unit. Freezing unit monitors temperature of cells themselves. Thermocouple placed against polyethylene container relays temperature signals to an electronic system which controls small heaters located outside container. Heaters allow liquid nitrogen to circulate at constant temperature and maintain consistent freezing rate. Ability to freeze, store, and thaw white cells and bone marrow without damage is important in leukemia treatment.

Source record↗

Effects of exposure to simulated microgravity on neuronal catecholamine release and blood pressure responses to norepinephrine and angiotensin

We tested the hypothesis that exposure to microgravity reduces the neuronal release of catecholamines and blood pressure responses to norepinephrine and angiotensin. Eight men underwent 30 days of 6 degrees head-down tilt (HDT) bedrest to simulate exposure to microgravity. Plasma norepinephrine and mean arterial blood pressure (MAP) were measured before and after a cold pressor test (CPT) and graded norepinephrine infusion (8, 16 and 32 ng/kg/min) on day 6 of a baseline control period (C6) and on days 14 and 27 of HDT. MAP and plasma angiotensin II (Ang-II) were measured during graded Ang-II infusion (1, 2 and 4 ng/kg/min) on C8 and days 16 and 29 of HDT. Baseline total circulating norepinephrine was reduced from 1017ng during the baseline control period to 610 ng at day 14 and 673ng at day 27 of HDT, confirming a hypoadrenergic state. An elevation of norepinephrine (+178 ng) to the CPT during the baseline control period was eliminated by HDT days 14 and 27. During norepinephrine infusion, similar elevations in plasma norepinephrine (7.7 pg/ml/ng/kg/min) caused similar elevations in MAP (0.12 mmHg/ng/kg/min) across all test days. Ang-II infusion produced higher levels of plasma Ang-II during HDT (47.3 pg/ml) than during baseline control (35.5 pg/ml), while producing similar corresponding elevations in blood pressure. While vascular responsiveness to norepinephrine appears unaffected, impaired neuronal release of norepinephrine and reduced vascular responsiveness to Ang-II might contribute to the lessened capacity to vasoconstrict after spaceflight. The time course of alterations indicates effects that occur within two weeks of exposure.

NASA Center HQS↗

Application of acute maximal exercise to protect orthostatic tolerance after simulated microgravity

We tested the hypothesis that one bout of maximal exercise performed at the conclusion of prolonged simulated microgravity would improve blood pressure stability during an orthostatic challenge. Heart rate (HR), mean arterial blood pressure (MAP), norepinephrine (NE), epinephrine (E), arginine vasopressin (AVP), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cardiac output (Q), forearm vascular resistance (FVR), and changes in leg volume were measured during lower body negative pressure (LBNP) to presyncope in seven subjects immediately prior to reambulation from 16 days of 6 degrees head-down tilt (HDT) under two experimental conditions: 1) after maximal supine cycle ergometry performed 24 h before returning to the upright posture (exercise) and 2) without exercise (control). After HDT, the reduction of LBNP tolerance time from pre-HDT levels was greater (P = 0.041) in the control condition (-2.0 +/- 0.2 min) compared with the exercise condition (-0.4 +/- 0.2 min). At presyncope after HDT, FVR and NE were higher (P < 0.05) after exercise compared with control, whereas MAP, HR, E, AVP, PRA, ANP, and leg volume were similar in both conditions. Plasma volume (PV) and carotid-cardiac baroreflex sensitivity were reduced after control HDT, but were restored by the exercise treatment. Maintenance of orthostatic tolerance by application of acute intense exercise after 16 days of simulated microgravity was associated with greater circulating levels of NE, vasoconstriction, Q, baroreflex sensitivity, and PV.

NASA Discipline Cardiopulmonary↗

Cardiovascular studies in the rhesus monkey

Criteria are given for selecting the macaca mulatta as the analogue of the human in the study of cerebral circulation, particularly the control of the cerebral vascular bed during normal and stressful conditions. Topics discussed include surgical preparation of subject; responses to changes in arterial pressure, oxygen, and carbon dioxide; innervation of cerebral vessels; cerebral flow response to acceleration; and cerebral blood flow and cerebellar stimulation.

Stone, H. L.↗

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethys-mography of supine health male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n equals 6) and during placebo infusion (n equals 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 plus or minus 4 to 2,568 plus or minus 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion; mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3 percent respectively, relative to pre-infusion baseline values (p is less than 0.05). Mean calf filtration, however was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20 percent with ANP infusion, wheras blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, phamacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchic sites or both, while having the opposite effect in the leg.

Watenpaugh, Donald E.↗

Antiorthostatic hypokinesia and circulation in the rat

Circulatory mechanisms that occur during exposure to head-down hypokinesia as well as during readaptation to control conditions were studied on unanesthetized unrestrained Sprague-Dawley rats exposed to hypokinesia for seven days. The heart rate was slightly elevated, and the right atrial pressure increased to 4 mm Hg, but returned to 0 mm Hg after three days of exposure. Mean arterial blood pressure decreased from 118 to 100 mm Hg during early exposure to antiorthostatic hypokinesia. Cardiac output and stroke volume of resting rats increased during early exposure to hypokinesia but decreased continuously during the next seven days. The results indicate that antiorthostatic hypokinesia induces circulatory changes similar to those seen in astronauts after several days of exposure to 0 g forces.

Popovic, V.↗

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

vascular↗

Pharmacologic Atrial Natriuretic Peptide Reduces Human Leg Capillary Filtration

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma (ANP) from 30 +/- 4 to 2,568 +/- 595 pmol/L. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p less than 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/ arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.

Watenpaugh, Donald E.↗

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

NASA Discipline Cardiopulmonary↗

Neocytolysis: physiological down-regulator of red-cell mass

It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

Review, Tutorial↗

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.

Non-NASA Center↗

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↗

Development of a hydraulic model of the human systemic circulation

Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

NASA Program Biomedical Research and Countermeasur↗

Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous micro- circulation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, 0 deg, -6 deg (HDT), -12 deg, -6 deg, 0 deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P < 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar-X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

Breit, Gregory A.↗

Effects of the oral contraceptive pill cycle on physiological responses to hypoxic exercise

To test whether the oral contraceptive pill cycle affects endocrine and metabolic responses to hypoxic (fraction of inspired oxygen = 13%, P(IO2): 95 mmHg; H) versus normoxic (P(IO2):153 mmHg; N) exercise, we examined eight women (28 +/- 1.2 yr) during the third (PILL) and placebo (PLA) weeks of their monthly oral contraceptive pill cycle. Cardiopulmonary, metabolic, and neuroendocrine measurements were taken before, during, and after three 5-min consecutive workloads at 30%, 45%, and 60% of normoxic V(O2peak) in H and N trials. Heart rate response to exercise was greater in H versus N, but was not different between PILL and PLA. Lactate levels were significantly greater during exercise, and both lactate and glucose levels were significantly greater for 30 min after exercise in H versus N (p < 0.0001). When expressed relative to baseline, lactate levels were lower in PILL versus PLA, but glucose was greater in PILL versus PLA (p < 0.001). Cortisol levels were also significantly greater in PILL versus PLA (p < 0.001). Norepinephrine levels were significantly increased during exercise (p < 0.0001) and in H versus N (p < 0.0001). However, epinephrine levels were not different over time or with trial. Thus, the presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.

Non-NASA Center↗

Age, splanchnic vasoconstriction, and heat stress during tilting

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

NASA Discipline Cardiopulmonary↗

Design of evaporator of spacelab refrigerator/freezer

An Evaporator has been designed for NASA-Johnson Space Center Life Sciences to conduct experiments in Spacelab mission SLS-1 using different samples such as blood, urine, human tissues etc. Two units will fly - one as a Refrigerator (4 C) and the other as a Freezer (-22 C). The evaporator tube is dip brazed on a grooved flat plate. Aluminum heat sink is dip brazed on the other side of the plate. Freon R5O2 is pumped through the tube and air is circulated over the finned surface to transfer heat. As freon 5O2 is considered toxic, the whole freon tube is covered with an evaporator cover to contain any freon leakage to avoid exposure to crew members. This containment is under vacuum and this pressure is monitored along with the freon pressure to determine freon leakage so that necessary steps can be taken to stop contamination of the spacelab air. An stress analysis has been done and it is found to have adequate safety margin to meet the requirements of NASA safety and reliability standards.

Hye, A.↗