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Biomedical subjects

J B West

Publications and source records attributed to J B West.

At least 73 records · Page 4Linked to original sources

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity.

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Blood Gas Analysis↗

High vascular and airway pressures increase interstitial protein mRNA expression in isolated rat lungs.

We hypothesized that wall stresses produced by high peak airway (Paw) and venous (Ppv) pressures would increase mRNA levels for structural proteins of the interstitial matrix in isolated rat lungs. Groups of lungs (n = 6) were perfused for 4 h at a peak Paw of 35 cmH2O (HiPaw), cyclical peak Ppv of 28 cmH2O (HiPv), or baseline vascular and airway pressures (LoPress). In two separate groups, comparable peak pressures increased capillary filtration coefficient fourfold in each group. Northern blots were probed for mRNA of alpha 1(I), alpha 1(III), and alpha 2(IV) procollagen chains, laminin B chain, fibronectin, and transforming growth factor-beta 1, and densities were normalized to 18S rRNA. mRNA was significantly higher in the HiPv group for type I (4.3-fold) and type III (3.8-fold) procollagen and laminin B chain (4.8-fold) and in the HiPaw group for type I (2.4-fold) and type IV (4.5-fold) procollagen and laminin B chain (2.3-fold) than in the LoPress group. Only fibronectin mRNA was significantly increased (3.9-fold) in the LoPress group relative to unperfused lungs. Estimated wall stresses were highest for alveolar septa in the HiPaw group and for capillaries in the HiPv group. The different patterns of mRNA expression are attributed to different regional stresses or extent of injury.

Air Pressure↗

Effect of microgravity and hypergravity on deposition of 0.5- to 3-micron-diameter aerosol in the human lung.

We measured intrapulmonary deposition of 0. 5-, 1-, 2-, and 3-micron-diameter particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and at approximately 1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidal volume (0.75 liter). At 1 G and approximately 1.6 G, deposition increased with increasing particle size. In microG, differences in deposition as a function of particle size were almost abolished. Deposition was a nearly linear function of the G level for 2- and 3-micron-diameter particles, whereas for 0.5- and 1.0-micron-diameter particles, deposition increased less between microG and 1 G than between 1 G and approximately 1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-micron-diameter particles at 1 and approximately 1.6 G, whereas the model consistently underestimated deposition in microG. The higher deposition observed in microG compared with model predictions might be explained by a larger deposition by diffusion because of a higher alveolar concentration of aerosol in microG and to the nonreversibility of the flow, causing additional mixing of the aerosols.

Adult↗

Intense exercise impairs the integrity of the pulmonary blood-gas barrier in elite athletes.

The blood-gas barrier must be very thin to allow gas exchange and it is therefore subjected to high mechanical stresses when the capillary pressure rises. In some animals, such as the thoroughbred race-horse during intense exercise, the stresses are so large that the capillaries fail and bleeding occurs. We tested the hypothesis that, in elite human athletes, the high capillary pressure that occurs during severe exercise alters the structure and function of the blood-gas barrier. We performed bronchoalveolar lavage (BAL) in six healthy athletes, who had a history suggestive of lung bleeding, 1 h after a 7-min cycling race simulation and four normal sedentary control subjects who did not exercise before BAL. The athletes had higher (p < 0.05) concentrations of red blood cells (0.51 x 10(5) versus 0.01 x 10(5).ml-1), total protein (128.0 versus 94.1 micrograms/ml), albumin (65.6 versus 53.0 micrograms/ml), and leukotriene B4 (LTB4) (243 versus 0 pg/ml) in BAL fluid than control subjects. The proportion of neutrophils was similar in athletes and control subjects but the proportion of lymphocytes in BAL fluid was reduced (p < 0.05). There were no differences in levels of surfactant apoprotein A, tumor necrosis factor bioactivity, lipopolysaccharide, or interleukin-8 (IL-8) between groups. These results show that brief intense exercise in athletes with a history suggestive of lung bleeding alters blood-gas barrier function resulting in higher concentrations of red cells and protein in BAL fluid. The lack of activation of proinflammatory pathways (except LTB4) in the airspaces supports the hypothesis that the mechanism for altered blood-gas barrier function is mechanical stress.

Adult↗

Fire hazard in oxygen-enriched atmospheres at low barometric pressures.

Pilot studies are presently being carried out to determine the efficacy of raising the oxygen concentration in the room air of commercial and scientific facilities at altitudes of 4000-5500 m. This is a remarkably effective way of relieving hypoxia. For example, oxygen enrichment by only 5% (i.e., raising the oxygen concentration from 21 to 26%) reduces the equivalent altitude by 1500 m. However, concern has been expressed about the possibility of fire hazard. In this article, existing data from various sources have been analyzed to determine the burning rate of materials such as paper and cotton clothing at various altitudes when the PO2 in the air is increased to 110 mmHg to give an equivalent altitude of 3000 m. The analysis shows that in spite of the increase in oxygen concentration, the burning rate is much less than at sea level primarily because the PO2 is so much lower even with oxygen enrichment.

Altitude↗

T.H. Ravenhill and his contributions to mountain sickness.

Thomas Holmes Ravenhill (1881-1952) was an important pioneer in high-altitude medicine but almost nothing has been published about him. He wrote a landmark paper in 1913 that included the classification of high-altitude sickness that is still in use, and it also contained the first accurate descriptions of high-altitude pulmonary edema and high-altitude cerebral edema, although he used different terms. The work was done while he was medical officer at the Collahuasi and Poderosa mines in northern Chile at altitudes he gave as 4,690-4,940 m. Remarkably, the paper was then forgotten until it was rediscovered over 50 yr later, but it is now cited in any comprehensive study of high-altitude illness. Ravenhill graduated in medicine from the University of Birmingham, Birmingham, UK, in 1905 and 4 yr later went to the mines where he spent 2 yr. Subsequently, he served in the Royal Army Medical Corps in the 1914-1918 war and was awarded the Military Cross. He returned to general practice but after a few years gave up medicine altogether. He then made important contributions to archeology and spent the last third of his life in London as a painter, mainly in watercolors. It is unclear to what extent his war experiences brought about his dramatic career change.

Altitude Sickness↗

Anomalous behavior of helium and sulfur hexafluoride during single-breath tests in sustained microgravity.

We performed single-breath wash-in tests for He and SF6 in four subjects exposed to 14 days of microgravity (microG) during the Spacelab flight Spacelab Life Sciences-2. Subjects inspired a vital capacity breath of 5% He-1.25% SF6-balance O2 and then exhaled to residual volume at 0.5l/s. The tests were also performed with a 10-s breath hold at the end of inspiration. Measurements were also made with the subjects standing and supine in 1 G. Phase III slope was measured after the dead-space washout and before the onset of airway closure. In all subjects in 1 G, whether standing or supine, phase III slope for SF6 was significantly steeper than that for He. However, in microG, the slopes became the same. Furthermore, after breath holding in microG, the SF6 slopes were significantly flatter than those for He. On return to 1 G, the changes were reversed, and there was no difference between preflight and postflight values. Because most of the phase III slope reflects events occurring in the acinar regions of the lung, the results suggest that microG causes conformational changes in the acini or changes in cardiogenic mixing in the lung periphery, but in either case the mechanism is unclear.

Adult↗

Forced expirations and maximum expiratory flow-volume curves during sustained microgravity on SLS-1.

Gravity is known to influence the mechanical behavior of the lung and chest wall. However, the effect of sustained microgravity (microG) on forced expirations has not previously been reported. Tests were carried out by four subjects in both the standing and supine postures during each of seven preflight and four postflight data-collection sessions and four times during the 9 days of microG exposure on Spacelab Life Sciences-1. Compared with preflight standing values, peak expiratory flow rate (PEFR) was significantly reduced by 12.5% on flight day 2 (FD2), 11.6% on FD4, and 5.0% on FD5 but returned to standing values by FD9. The supine posture caused a 9% reduction in PEFR. Forced vital capacity and forced expired volume in 1 s were slightly reduced (approximately 3-4%) on FD2 but returned to preflight standing values on FD4 and FD5, and by FD9 both values were slightly but significantly greater than standing values. Forced vital capacity and forced expiratory volume in 1 s were both reduced in the supine posture (approximately 8-10%). Forced expiratory flows at 50% and between 25 and 75% of vital capacity did not change during microG but were reduced in the supine posture. Analysis of the maximum expiratory flow-volume curve showed that microG caused no consistent change in the curve configuration when individual in-flight days were compared with preflight standing curves, although two subjects did show a slight reduction in flows at low lung volumes from FD2 to FD9. The interpretation of the lack of change in curve configuration must be made cautiously because the lung volumes varied from day to day in flight. Therefore, the flows at absolute lung volumes in microG and preflight standing are not being compared. The supine curves showed a subtle but consistent reduction in flows at low lung volumes. The mechanism responsible for the reduction in PEFR is not clear. It could be due to a lack of physical stabilization when performing the maneuver in the absence of gravity or a transient reduction in respiratory muscle strength.

Adult↗

Prediction of barometric pressures at high altitude with the use of model atmospheres.

It would be valuable to have model atmospheres that allow barometric pressures (PB) to be predicted at high altitudes. Attempts to do this in the past using the International Civil Aviation Organizations or United States Standard Atmosphere model have brought such models into disrepute because the predicted pressures at high altitudes are usually much too low. However, other model atmospheres have been developed by geophysicists. The critical variable is the change of air temperature with altitude, and, therefore, model atmospheres have been constructed for different latitudes and seasons of the year. These different models give a large range of pressures at a given altitude. For example, the maximum difference of pressure at an altitude of 9 km is from 206 to 248 Torr, i.e., approximately 20%. However, the mean of the model atmospheres for latitude of 15 degrees (in all seasons) and 30 degrees (in the summer) predicts PB at many locations of interest at high altitude very well, with predictions within 1%. The equation is PB (Torr) = exp (6.63268 - 0.1112 h - 0.00149 h2), were h is the altitude in kilometers. The predictions are good because many high mountain sites are within 30 degrees of the equator and also many studies are made during the summer. Other models should be used for latitudes of 45 degrees and above. Model atmospheres have considerable value in predicting PB at high altitude if proper account is take of latitude and season of the year.

Altitude↗

High altitude medicine and physiology in the former Soviet Union.

The countries of the former Soviet Union have a long history of studies in high-altitude medicine and physiology, but much of the information is difficult to obtain in the West because of the inaccessibility of the journals and the lack of familiarity with the language. The purpose of present review is to improve this situation. In the 1880's, Ivan Sechenov (1829-1905), one of the founders of the Russian school of physiology, introduced the notion of the "inner altitude," that is, how the alveolar Po2 changes with barometric pressure. Later in the 19th century, Russian army physicians made extensive studies of the fitness of soldiers at high altitude and of procedures for improving acclimatization. With the birth of Soviet mountaineering in 1923, a large series of expeditions went to high altitude, first in the Alps, and later in the Caucasus. Nikolay N. Sirotinin (1896-1977) led 9 pre-war research expeditions to Mt. Elbrus and other areas, and, because he thought the alkalosis was partly responsible for mountain sickness, he introduced acid mixtures to be taken orally. Zoia I. Barbashova (1910-1980) made extensive studies of tissue adaptation, especially enzyme activities, in animals exposed to hypoxia. More recently Oleg G. Gazenko (1918-) and his colleagues have carried out extensive studies associated with aviation medicine and the selection of cosmonauts for the Soviet space program. Among many topics, one is the study of how adaptation to one type of physiologic stress (e.g., hypoxia) can improve tolerance to another stress (e.g., acceleration).

Altitude↗

Vulnerability of pulmonary capillaries in heart disease.

The pulmonary blood-gas barrier presents a dilemma. It must be extremely thin for efficient gas exchange. However, it also needs to be immensely strong because the stresses in the pulmonary capillary wall become extremely high when the capillary pressure rises. Stress failure of the capillaries occurs in several pathological conditions. It causes high-permeability edema as in neurogenic pulmonary edema or high-altitude pulmonary edema; alveolar hemorrhage, which occurs in all galloping racehorses; or a combination of the two as in severe congestive heart failure. The vulnerability of the capillary wall to increased mechanical stress has not previously been sufficiently appreciated.

Animals↗

Effect of increased duration of high perfusion pressure on stress failure of pulmonary capillaries.

We have previously shown that raising the capillary transmural pressure (Ptm) in rabbit lung causes disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers of the wall. In those studies the lungs were perfused with autologous blood (1 min), then saline/dextran (3 min), followed by glutaraldehyde fixative (10 min), all at the same pressure. The present study was designed to determine whether increasing the time of exposure of the capillaries to the increased pressure altered the frequency of stress failure. The procedure was identical to that of the previous study except that the duration of the blood perfusion was extended from 1 to 10 and 100 min. We chose a Ptm of 32.5 cm H2O because our previous studies showed that this caused only a few disruptions per millimeter endothelial and epithelial boundary length (0.7 +/- 0.4 and 0.9 +/- 0.6 (SE), respectively). Ten New Zealand white rabbit lungs were perfused with autologous blood plus homologous blood from additional rabbits for 10 and 100 min. After 100 min of blood perfusion the number of disruptions per millimeter endothelial and epithelial boundary length (0.66 +/- 0.4 and 0.52 +/- 0.33 (SE), respectively) was not significantly different from the earlier study. Thus, increasing the duration of the increased Ptm during blood perfusion by 100-fold did not alter the incidence of stress failure. These results indicated that any viscoelastic behavior resulting in further strain and ultimately failure of the capillary walls is insignificant over a wide range of exposure times to increased pressure under the conditions of this study.

Animals↗

Stress failure of pulmonary capillaries as a limiting factor for maximal exercise.

The pulmonary blood-gas barrier has a basic physiological dilemma. On the one hand it needs to be extremely thin for efficient gas exchange. On the other hand it also needs to be immensely strong because the stresses on the pulmonary capillary wall become extremely high when the capillary pressure rises on exercise. Maximal hydrostatic pressures in human pulmonary capillaries during exercise are not accurately known but must exceed 30 mmHg. In some animals, for example thoroughbred horses, the capillary pressure rises to about 100 mmHg. These pressures cause stresses in the capillary wall of 5-10 x 10(4) N.m-2 (50-100 kPa) which approach the breaking strength of collagen. The strength of the capillary wall on the thin side of the blood-gas barrier can be attributed to the type IV collagen of the extracellular matrix. Raising the capillary pressure to similar levels in experimental preparations causes ultrastructural changes in the wall including disruption of the capillary endothelium, alveolar epithelium, and basement membrane in the interstitium. Essentially all thoroughbred racehorses bleed into their lungs during exercise because they break their capillaries, and some elite human athletes apparently do the same. Avoiding stress failure of pulmonary capillaries poses a challenging problem for some species. Stress failure is a hitherto overlooked factor limiting maximal exercise.

Animals↗

Oxygen enrichment of room air to relieve the hypoxia of high altitude.

Recently there has been increasing commercial activity at altitudes of 3500-6000 m. Examples include new mines in northern Chile at altitudes of about 4500 m. Because the workers come from sea level, intolerance of the high altitude is a major problem. This degree of hypoxia reduces work capacity, mental efficiency and sleep quality. One novel solution is to raise the PO2 of the room air by adding oxygen to the room ventilation. This is remarkably effective. For example, at altitudes of 4000-5000 m, increasing the O2 concentration by 1% (e.g. from 21 to 22%) reduces the equivalent altitude by about 300 m. Thus raising the O2 concentration by 5% at the new mines reduces the equivalent altitude to 3000 m which is easily tolerated. The introduction of oxygen concentrators (molecular sieve) which require only electrical power makes O2 enrichment feasible. The fire hazard is less than in air at sea level. Everybody now expects that the ventilation of a room will provide a comfortable temperature and humidity. Control of the oxygen concentration can be regarded as a further logical step in man's control of his environment.

Altitude↗

Ventilatory inhomogeneity determined from multiple-breath washouts during sustained microgravity on Spacelab SLS-1.

We used multiple-breath N2 washouts (MBNW) to study the inhomogeneity of ventilation in four normal humans (mean age 42.5 yr) before, during, and after 9 days of exposure to microgravity on Spacelab Life Sciences-1. Subjects performed 20-breath MBNW at tidal volumes of approximately 700 ml and 12-breath MBNW at tidal volumes of approximately 1,250 ml. Six indexes of ventilatory inhomogeneity were derived from data from 1) distribution of specific ventilation (SV) from mixed-expired and 2) end-tidal N2, 3) change of slope of N2 washout (semilog plot) with time, 4) change of slope of normalized phase III of successive breaths, 5) anatomic dead space, and 6) Bohr dead space. Significant ventilatory inhomogeneity was seen in the standing position at normal gravity (1 G). When we compared standing 1 G with microgravity, the distributions of SV became slightly narrower, but the difference was not significant. Also, there were no significant changes in the change of slope of the N2 washout, change of normalized phase III slopes, or the anatomic and Bohr dead spaces. By contrast, transition from the standing to supine position in 1 G resulted in significantly broader distributions of SV (P < 0.05) and significantly greater changes in the changes in slope of the N2 washouts (P < 0.001), indicating more ventilatory inhomogeneity in that posture. Thus these techniques can detect relatively small changes in ventilatory inhomogeneity. We conclude that the primary determinants of ventilatory inhomogeneity during tidal breathing in the upright posture are not gravitational in origin.

Adult↗

Pulmonary capillaries are more resistant to stress failure in dogs than in rabbits.

We previously showed that stress failure of pulmonary capillaries occurs at transmural pressures of approximately 50 cmH2O (40 mmHg) and above in rabbit lung. In this study, we examined whether pulmonary capillaries are more resistant to failure in dogs than in rabbits. This might be expected because of the greater athletic ability of dogs and therefore their presumably greater tolerance to large cardiac outputs and higher pulmonary vascular pressures. The lungs of 12 anesthetized mongrel dogs [22.1 +/- 5.2 (SD) kg] were perfused in situ with autologous blood and then with saline-dextran (5 min) and glutaraldehyde solution (10 min), all three perfusions at the same preset transmural pressure of 32.5, 72.5, 92.5, or 112.5 cmH2O. In dogs, the stress failure curves relating break number per millimeter of epithelium and endothelium were right shifted by approximately 40 cmH2O compared with rabbits. Blood-gas barrier thickness was significantly greater than in rabbits at 32.5 cmH2O, and unlike in rabbits, neither total nor interstitial thickness increased significantly with increasing pressure. These results indicate that pulmonary capillaries are more resistant to stress failure in dogs than rabbits.

Animals↗