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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Role of metabolic gases in bubble formation during hypobaric exposures

Our hypothesis is that metabolic gases play a role in the initial explosive growth phase of bubble formation during hypobaric exposures. Models that account for optimal internal tensions of dissolved gases to predict the probability of occurrence of venous gas emboli were statistically fitted to 426 hypobaric exposures from National Aeronautics and Space Administration tests. The presence of venous gas emboli in the pulmonary artery was detected with an ultrasound Doppler detector. The model fit and parameter estimation were done by using the statistical method of maximum likelihood. The analysis results were as follows. 1) For the model without an input of noninert dissolved gas tissue tension, the log likelihood (in absolute value) was 255.01. 2) When an additional parameter was added to the model to account for the dissolved noninert gas tissue tension, the log likelihood was 251.70. The significance of the additional parameter was established based on the likelihood ratio test (P < 0.012). 3) The parameter estimate for the dissolved noninert gas tissue tension participating in bubble formation was 19. 1 kPa (143 mmHg). 4) The additional gas tissue tension, supposedly due to noninert gases, did not show an exponential decay as a function of time during denitrogenation, but it remained constant. 5) The positive sign for this parameter term in the model is characteristic of an outward radial pressure of gases in the bubble. This analysis suggests that dissolved gases other than N2 in tissues may facilitate the initial explosive bubble-growth phase.

NASA Center JSC↗
NASA NTRS1997

Pulmonary function in space

The lung is exquisitely sensitive to gravity, and so it is of interest to know how its function is altered in the weightlessness of space. Studies on National Aeronautics and Space Administration (NASA) Spacelabs during the last 4 years have provided the first comprehensive data on the extensive changes in pulmonary function that occur in sustained microgravity. Measurements of pulmonary function were made on astronauts during space shuttle flights lasting 9 and 14 days and were compared with extensive ground-based measurements before and after the flights. Compared with preflight measurements, cardiac output increased by 18% during space flight, and stroke volume increased by 46%. Paradoxically, the increase in stroke volume occurred in the face of reductions in central venous pressure and circulating blood volume. Diffusing capacity increased by 28%, and the increase in the diffusing capacity of the alveolar membrane was unexpectedly large based on findings in normal gravity. The change in the alveolar membrane may reflect the effects of uniform filling of the pulmonary capillary bed. Distributions of blood flow and ventilation throughout the lung were more uniform in space, but some unevenness remained, indicating the importance of nongravitational factors. A surprising finding was that airway closing volume was approximately the same in microgravity and in normal gravity, emphasizing the importance of mechanical properties of the airways in determining whether they close. Residual volume was unexpectedly reduced by 18% in microgravity, possibly because of uniform alveolar expansion. The findings indicate that pulmonary function is greatly altered in microgravity, but none of the changes observed so far will apparently limit long-term space flight. In addition, the data help to clarify how gravity affects pulmonary function in the normal gravity environment on Earth.

short duration↗
NASA NTRS1992

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure

We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS).

Non-NASA Center↗
NASA NTRS2000

Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia

To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

Non-NASA Center↗
NASA NTRS1977

Mathematical modelling of a human external respiratory system

A closed system of algebraic and common differential equations solved by computer is investigated. It includes equations which describe the activity pattern of the respiratory center, the phrenic nerve, the thrust produced by the diaphragm as a function of the lung volume and discharge frequency of the phrenic nerve, as well as certain relations of the lung stretch receptors and chemoreceptors on various lung and blood characteristics, equations for lung biomechanics, pulmonary blood flow, alveolar gas exchange and capillary blood composition equations to determine various air and blood flow and gas exchange parameters, and various gas mixing and arterial and venous blood composition equations, to determine other blood, air and gas mixing characteristics. Data are presented by means of graphs and tables, and some advantages of this model over others are demonstrated by test results.

Source record↗
NASA NTRS1992

Ventilation-perfusion matching during exercise

In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.

Non-NASA Center↗
NASA NTRS1998

Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

Non-NASA Center↗
NASA NTRS2004

Investigations of Pulmonary Epithelial Cell Damage due to Air-Liquid Interfacial Stresses in a Microgravity Environment

Pulmonary airway closure is a potentially dangerous event that can occur in microgravity environments and may result in limited gas exchange for flight crew during long-term space flight. Repetitive airway collapse and reopening subjects the pulmonary epithelium to large, dynamic, and potentially injurious mechanical stresses. During ventilation at low lung volumes and pressures, airway instability leads to repetitive collapse and reopening. During reopening, air must progress through a collapsed airway, generating stresses on the airway walls, potentially damaging airway tissues. The normal lung can tolerate repetitive collapse and reopening. However, combined with insufficient or dysfunctional pulmonary surfactant, repetitive airway collapse and reopening produces severe lung injury. Particularly at risk is the pulmonary epithelium. As an important regulator of lung function and physiology, the degree of pulmonary epithelial damage influences the course and outcome of lung injury. In this paper we present experimental and computational studies to explore the hypothesis that the mechanical stresses associated with airway reopening inflict injury to the pulmonary epithelium.

Gaver, Donald P., III↗
NASA NTRS1999

Effect of furosemide on pulmonary blood flow distribution in resting and exercising horses

We determined the spatial distribution of pulmonary blood flow (PBF) with 15-micron fluorescent-labeled microspheres during rest and exercise in five Thoroughbred horses before and 4 h after furosemide administration (0.5 mg/kg iv). The primary finding of this study was that PBF redistribution occurred from rest to exercise, both with and without furosemide. However, there was less blood flow to the dorsal portion of the lung during exercise postfurosemide compared with prefurosemide. Furosemide did alter the resting perfusion distribution by increasing the flow to the ventral regions of the lung; however, that increase in flow was abated with exercise. Other findings included 1) unchanged gas exchange and cardiac output during rest and exercise after vs. before furosemide, 2) a decrease in pulmonary arterial pressure after furosemide, 3) an increase in the slope of the relationship of PBF vs. vertical height up the lung during exercise, both with and without furosemide, and 4) a decrease in blood flow to the dorsal region of the lung at rest after furosemide. Pulmonary perfusion variability within the lung may be a function of the anatomy of the pulmonary vessels that results in a predominantly fixed spatial pattern of flow distribution.

NASA Discipline Cardiopulmonary↗
NASA NTRS1975

Fluctuations in O2 stores and gas exchange with passive changes in posture

The purpose of the present study is to determine the effects of changes in posture on oxygen transfer at the mouth and pulmonary capillary membrane and to observe concomitant subtle changes in ventilation under specified assumptions. Breath-by-breath calculations are carried out with a box-balloon spirometer and mass spectrometer. Measurements are made before, during, and after passive tilt to 60 deg and on return to recumbency after 10 min erect. It is found that from supine to upright oxygen stores in the lung increases rapidly and oxygen stores in the blood drops slowly, creating a net deficit in oxygen transfer at the mouth of 130 ml in 10 min. Changes in oxygen stores in the blood result from shifts in blood volume and flow more than from changes in cardiac output. Refilling of oxygen stores in the blood is found to cause transient hypoxia with substantial hyperpnea.

Loeppky, J. A.↗
NASA NTRS1991

Pathophysiology of spontaneous venous gas embolism

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Lambertsen, C. J.↗
NASA NTRS1992

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗
NASA NTRS1972

Effect of stratified inequality of blood flow on gas exchange in liquid-filled lungs.

This investigation set out to answer two questions: (1) are the distal alveoli in the terminal lung units less well perfused than the proximal alveoli, i.e., is there stratification of blood flow; and (2) if so, does this enhance gas exchange in the presence of stratified inequality of ventilation. Excised dog lungs were ventilated with saline and perfused with blood. Following single inspirations of xenon 133 in saline and various periods of breath holding, the expired xenon concentration against volume was measured and it confirmed marked stratified inequality of ventilation under these conditions. By measuring the rate of depletion of xenon from alveoli during a period of blood flow, we showed that the alveoli which emptied at the end of expiration had 16% less blood flow than those exhaling earlier. However, by measuring the xenon concentration in pulmonary venous blood, we found that about 10% less tracer was transferred from the alveoli into the blood when the inspired xenon was stratified within the respiratory zone. Thus while stratification of blood flow was confirmed, it was shown to impair rather than enhance the efficiency of gas transfer.

West, J. B.↗
NASA NTRS1972

Effects of diffusion impairment on O2 and CO2 time courses in pulmonary capillaries.

Simultaneous time courses for O2 and CO2 exchange along the capillary have been calculated for homogeneous lungs, allowing for O2-CO2 interactions, dissolved O2, and chemical reaction rates. As diffusing capacity (Dl) was reduced, the transfer of CO2 and O2 was impaired by similar amounts, in spite of the 20-fold greater diffusing capacity for CO2. The reason why CO2 is affected so much is that the slope of the content against partial pressure is so much greater in blood than tissue for this gas. Because of the shapes of their respective dissociation curves, O2 transfer was most affected at normal ventilation-perfusion ratios, whereas CO2 was most affected at high ratios. Exercise exaggerated the impairment of transfer of both gases.

Wagner, P. D.↗
NASA NTRS1986

An analysis of estimation of pulmonary blood flow by the single-breath method

The single-breath method represents a simple noninvasive technique for the assessment of capillary blood flow across the lung. However, this method has not gained widespread acceptance, because its accuracy is still being questioned. A rigorous procedure is described for estimating pulmonary blood flow (PBF) using data obtained with the aid of the single-breath method. Attention is given to the minimization of data-processing errors in the presence of measurement errors and to questions regarding a correction for possible loss of CO2 in the lung tissue. It is pointed out that the estimations are based on the exact solution of the underlying differential equations which describe the dynamics of gas exchange in the lung. The reported study demonstrates the feasibility of obtaining highly reliable estimates of PBF from expiratory data in the presence of random measurement errors.

Srinivasan, R.↗
NASA NTRS2018

Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight.

Portable Pulmonary Function System (PPFS)↗
NASA NTRS2003

Validation of measurements of ventilation-to-perfusion ratio inequality in the lung from expired gas

The analysis of the gas in a single expirate has long been used to estimate the degree of ventilation-perfusion (Va/Q) inequality in the lung. To further validate this estimate, we examined three measures of Va/Q inhomogeneity calculated from a single full exhalation in nine anesthetized mongrel dogs under control conditions and after exposure to aerosolized methacholine. These measurements were then compared with arterial blood gases and with measurements of Va/Q inhomogeneity obtained using the multiple inert gas elimination technique. The slope of the instantaneous respiratory exchange ratio (R slope) vs. expired volume was poorly correlated with independent measures, probably because of the curvilinear nature of the relationship due to continuing gas exchange. When R was converted to the intrabreath Va/Q (iV/Q), the best index was the slope of iV/Q vs. volume over phase III (iV/Q slope). This was strongly correlated with independent measures, especially those relating to inhomogeneity of perfusion. The correlations for iV/Q slope and R slope considerably improved when only the first half of phase III was considered. We conclude that a useful noninvasive measurement of Va/Q inhomogeneity can be derived from the intrabreath respiratory exchange ratio.

NASA Discipline Cardiopulmonary↗
NASA NTRS1997

Hypergravity Alters the Susceptibility of Cells to Anoxia-Reoxygenation Injury

Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?

McCloud, Henry↗