Distribution of pulmonary blood flow.
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Australia↗
Biomedical subjects
J B West
Publications and source records attributed to J B West.
Commuting to high altitude. Recent studies of oxygen enrichment.
Further studies have been carried out on the potential value of oxygen enrichment of room air for commuters to high altitude. Novel ways of providing oxygen-enriched spaces for working and sleeping are being tested at the California Institute of Technology where a radiotelescope is being designed for an altitude of 5,000 m in north Chile. The modules are containers such as those used on container ships, and they are fitted out in California and then sealed and transported to the telescope site in Chile. The result is a turnkey facility which shows promise for field studies. The oxygen is provided by oxygen concentrators, and different modules are used for sleeping, living, and laboratory quarters. Two extensive experiments on oxygen enrichment were carried out at the University of California White Mountain Research Station, altitude 3,800 m, in the summer of 1998. The first study was devoted to the mechanism for the increase in arterial oxygen saturation on the day after sleeping in an oxygen-enriched atmosphere compared with sleeping in ambient air (5). Possible mechanisms include less fluid accumulation in the lung associated with acute mountain sickness, or a change in the control of ventilation. A double blind study was therefore carried out of the effects of sleeping in oxygen enrichment on both the ventilatory response to hypoxia and to carbon dioxide. In a related study, subjects who had been at an altitude of 3,800 m for two days, and were therefore partially acclimatized, were studied at a simulated altitude of 5,000 both breathing ambient air and 27% oxygen. The studies were done at 3800 m altitude by enriching the atmosphere of the test room with appropriate amounts of nitrogen or oxygen. An extensive series of neuropsychological tests were carried out with the objective of determining which features of CNS function were improved by oxygen enrichment at an altitude of 5,000 m.
Altitude↗
Space medicine in peer-reviewed journals: reply.
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Aerospace Medicine↗
Room oxygen enrichment improves sleep and subsequent day-time performance at high altitude.
We carried out a randomized, double-blind trial at 3800 m altitude to test whether a small degree of room oxygen enrichment at night improves sleep quality, and performance and well-being the following day. Eighteen sea-level residents drove from sea level to 3800 m in one day, and then slept one night in ambient air, and another night in 24% oxygen, the order being randomized. With oxygen enrichment the subjects had fewer apneas (P < 0.01) and spent less time in periodic breathing with apneas (P < 0.01) than when they slept in ambient air. Subjective assessments of sleep quality were also significantly improved. There was a lower acute mountain sickness score during the morning after oxygen-enriched sleep (P < 0.01) and a greater increase in arterial oxygen saturation from evening to morning (P < 0.05). The larger increases in arterial oxygen saturation from evening to morning suggest that the control of breathing may have been altered. Installing an oxygen-enriched room at high altitude is relatively simple and inexpensive, and shows promise for improving well-being of both commuters and residents.
Adult↗
Predicting error in rigid-body point-based registration.
Guidance systems designed for neurosurgery, hip surgery, and spine surgery, and for approaches to other anatomy that is relatively rigid can use rigid-body transformations to accomplish image registration. These systems often rely on point-based registration to determine the transformation, and many such systems use attached fiducial markers to establish accurate fiducial points for the registration, the points being established by some fiducial localization process. Accuracy is important to these systems, as is knowledge of the level of that accuracy. An advantage of marker-based systems, particularly those in which the markers are bone-implanted, is that registration error depends only on the fiducial localization error (FLE) and is thus to a large extent independent of the particular object being registered. Thus, it should be possible to predict the clinical accuracy of marker-based systems on the basis of experimental measurements made with phantoms or previous patients. This paper presents two new expressions for estimating registration accuracy of such systems and points out a danger in using a traditional measure of registration accuracy. The new expressions represent fundamental theoretical results with regard to the relationship between localization error and registration error in rigid-body, point-based registration. Rigid-body, point-based registration is achieved by finding the rigid transformation that minimizes "fiducial registration error" (FRE), which is the root mean square distance between homologous fiducials after registration. Closed form solutions have been known since 1966. The expected value (FRE2) depends on the number N of fiducials and expected squared value of FLE, (FLE-2, but in 1979 it was shown that (FRE2) is approximately independent of the fiducial configuration C. The importance of this surprising result seems not yet to have been appreciated by the registration community: Poor registrations caused by poor fiducial configurations may appear to be good due to a small FRE value. A more critical and direct measure of registration error is the "target registration error" (TRE), which is the distance between homologous points other than the centroids of fiducials. Efforts to characterize its behavior have been made since 1989. Published numerical simulations have shown that (TRE2) is roughly proportional to (FLE2)/N and, unlike (FRE2), does depend in some way on C. Thus, FRE, which is often used as feedback to the surgeon using a point-based guidance system, is in fact an unreliable indicator of registration-accuracy. In this work we derive approximate expressions for (TRE2), and for the expected squared alignment error of an individual fiducial. We validate both approximations through numerical simulations. The former expression can be used to provide reliable feedback to the surgeon during surgery and to guide the placement of markers before surgery, or at least to warn the surgeon of potentially dangerous fiducial placements; the latter expression leads to a surprising conclusion: Expected registration accuracy (TRE) is worst near the fiducials that are most closely aligned! This revelation should be of particular concern to surgeons who may at present be relying on fiducial alignment as an indicator of the accuracy of their point-based guidance systems.
Humans↗
Multiple-breath washin of helium and sulfur hexafluoride in sustained microgravity.
We performed multiple-breath washouts of N2 and simultaneous washins of He and SF6 with fixed tidal volume (approximately 1,250 ml) and preinspiratory lung volume (approximately the subject's functional residual capacity in the standing position) in four normal subjects (mean age 40 yr) standing and supine in normal gravity (1 G) and during exposure to sustained microgravity (microG). The primary objective was to examine the influence of diffusive processes on the residual, nongravitational ventilatory inhomogeneity in the lung in microG. We calculated several indexes of convective ventilatory inhomogeneity from each gas species. A normal degree of ventilatory inhomogeneity was seen in the standing position at 1 G that was largely unaltered in the supine position. When we compared the standing position in 1 G with microG, there were reductions in phase III slope in all gases, consistent with a reduction in convection-dependent inhomogeneity in the lung in microG, although considerable convective inhomogeneity persisted in microG. The reductions in the indexes of convection-dependent inhomogeneity were greater for He than for SF6, suggesting that the distances between remaining nonuniformly ventilated compartments in microG were short enough for diffusion of He to be an effective mechanism to reduce gas concentration differences between them.
Adult↗
Cardiogenic oscillation phase relationships during single-breath tests performed in microgravity.
We studied the phase relationships of the cardiogenic oscillations in the phase III portion of single-breath washouts (SBW) in normal gravity (1 G) and in sustained microgravity (microG). The SBW consisted of a vital capacity inspiration of 5% He-1.25% sulfurhexafluoride-balance O2, preceded at residual volume by a 150-ml Ar bolus. Pairs of gas signals, all of which still showed cardiogenic oscillations, were cross-correlated, and their phase difference was expressed as an angle. Phase relationships between inspired gases (e.g., He) and resident gas (n2) showed no change from 1 G (211 +/- 9 degrees) to microG (163 +/- 7 degrees). Ar bolus and He were unaltered between 1 G (173 +/- 15 degrees) and microG (211 +/- 25 degrees), showing that airway closure in microG remains in regions of high specific ventilation and suggesting that airway closure results from lung regions reaching low regional volume near residual volume. In contrast, CO2 reversed phase with He between 1 G (332 +/- 6 degrees) and microG (263 +/- 27 degrees), strongly suggesting that, in microG, areas of high ventilation are associated with high ventilation-perfusion ratio (VA/Q). This widening of the range of VA/Q in microG may explain previous measurements (G.K. Prisk, A.R. Elliott, H.J.B. Guy, J.M. Kosonen, and J.B. West J. Appl. Physiol. 79: 1290-1298, 1995) of an overall unaltered range of VA/Q in microG, despite more homogeneous distributions of both ventilation and perfusion.
Adult↗
Sustained submaximal exercise does not alter the integrity of the lung blood-gas barrier in elite athletes.
The extreme thinness of the pulmonary blood-gas barrier results in high mechanical stresses in the capillary wall when the capillary pressure rises during exercise. We have previously shown that, in elite cyclists, 6-8 min of maximal exercise increase blood-gas barrier permeability and result in higher concentrations of red blood cells, total protein, and leukotriene B4 in bronchoalveolar lavage (BAL) fluid compared with results in sedentary controls. To test the hypothesis that stress failure of the barrier only occurs at the highest level of exercise, we performed BAL in six healthy athletes after 1 h of exercise at 77% of maximal O2 consumption. Controls were eight normal nonathletes who did not exercise before BAL. In contrast with our previous study, we did not find higher concentrations of red blood cells, total protein, and leukotriene B4 in the exercising athletes compared with control subjects. However, higher concentrations of surfactant apoprotein A and a higher surfactant apoprotein A-to-phospholipid ratio were observed in the athletes performing prolonged exercise, compared with both the controls and the athletes from our previous study. These results suggest that, in elite athletes, the integrity of the blood-gas barrier is altered only at extreme levels of exercise.
Adult↗
Deposition and dispersion of 1-micrometer aerosol boluses in the human lung: effect of micro- and hypergravity.
We performed bolus inhalations of 1-micrometer particles in four subjects on the ground (1 G) and during parabolic flights both in microgravity (microG) and in approximately 1.6 G. Boluses of approximately 70 ml were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 200 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The deposition, dispersion, and position of the bolus in the expired gas were calculated from these data. For Vp >/=400 ml, both deposition and dispersion increased with Vp and were strongly gravity dependent, with the greatest deposition and dispersion occurring for the largest G level. At Vp = 800 ml, deposition and dispersion increased from 33.9% and 319 ml in microG to 56.9% and 573 ml at approximately 1.6 G, respectively (P < 0.05). At each G level, the bolus was expired at a smaller volume than Vp, and this volume became smaller with increasing Vp. Although dispersion was lower in microG than in 1 G and approximately 1.6 G, it still increased steadily with increasing Vp, showing that nongravitational ventilatory inhomogeneity is partly responsible for dispersion in the human lung.
Administration, Inhalation↗
Alveolar hypoxia increases gene expression of extracellular matrix proteins and platelet-derived growth factor-B in lung parenchyma.
The walls of pulmonary capillaries are extremely thin, and wall stress increases greatly when capillary pressure rises. Alveolar hypoxia causes pulmonary vasoconstriction and hypertension, and if this is uneven, some capillaries may be exposed to high transmural pressure and develop stress failure. There is evidence that increased wall stress causes capillary remodeling. In this study we exposed Madison strain Sprague-Dawley rats to normobaric hypoxia (10% oxygen) for 6 h or 3 d (short-term group), and for 3 d or 10 d (long-term group). Peripheral lung tissue was then collected and messenger RNA (mRNA) levels were determined for extracellular matrix (ECM) proteins and growth factors. Collagen content (hydroxyproline) was also measured. Levels of mRNA for alpha2(IV) procollagen increased sixfold after 6 h of hypoxia and sevenfold after 3 d of hypoxia, and then decreased after 10 d exposure. Levels of mRNA for platelet-derived growth factor-B (PDGF-B) doubled after 6 h of hypoxia but returned to control values after 3 d. mRNA levels for alpha1(I) and alpha1(III) procollagens and fibronectin were increased after 3 d of hypoxia (by seven- to 12-fold, 1.6- to eightfold, and 12-fold, respectively), then decreased toward control values after 10 d. In contrast, neither levels of mRNA for vascular endothelial growth factor (VEGF) nor collagen content changed. These results suggest that alveolar hypoxia causes vascular remodeling in lung parenchyma, and are consistent with capillary wall remodeling in response to increased wall stress.
Analysis of Variance↗
Left ventricular filling pressures during exercise: a cardiological blind spot?
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Animals↗
Yandell Henderson: April 23, 1873-February 18, 1944.
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Cardiology↗
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.
Humans↗
Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravity.
During single-breath washouts in normal gravity (1 G), the phase III slope of sulfur hexafluoride (SF6) is steeper than that of helium (He). Two mechanisms can account for this: 1) the higher diffusivity of He enhances its homogeneous distribution; and 2) the lower diffusivity of SF6 results in a more peripheral location of the diffusion front, where airway asymmetry is larger. These mechanisms were thought to be gravity independent. However, we showed during the Spacelab Life Sciences-2 spaceflight that in sustained microgravity (microG) the SF6-to-He slope difference is abolished. We repeated the protocol during short periods (27 s) of microG (parabolic flights). The subjects performed a vital-capacity inspiration and expiration of a gas containing 5% He-1.25% SF6-balance O2. As in sustained microG, the phase III slopes of He and SF6 decreased. However, during short-term microG, the SF6-to-He slope difference increased from 0.17 +/- 0.03%/l in 1 G to 0.29 +/- 0.06%/l in microG, respectively. This is contrary to sustained microG, in which the SF6-to-He slope difference decreased from 0.25 +/- 0.03%/l in 1 G to -0.01 +/- 0.06%/l in microG. The increase in phase III slope difference in short-term microG was caused by a larger decrease of He phase III slope compared with that in sustained microG. This suggests that changes in peripheral gas mixing seen in sustained microG are mainly due to alterations in the diffusive-convective inhomogeneity of He that require > 27 s of microG to occur. Changes in pulmonary blood volume distribution or cardiogenic mixing may explain the differences between the results found in short-term and sustained microG.
Adult↗
Very high pressures are required to cause stress failure of pulmonary capillaries in thoroughbred racehorses.
Thoroughbred horses develop extremely high pulmonary vascular pressures during galloping, all horses in training develop exercise-induced pulmonary hemorrhage, and we have shown that this is caused by stress failure of pulmonary capillaries. It is known that the capillary transmural pressure (Ptm) necessary for stress failure is higher in dogs than in rabbits. The present study was designed to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values (midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed, and samples (dorsal and ventral, from caudal region) were examined by electron microscopy. Few disruptions of capillary endothelium were observed at Ptm < or = 75 mmHg, and 5.3 +/- 2.2 and 4.3 +/- 0.7 breaks/mm endothelium were found at 100 and 150 mmHg Ptm, respectively. Blood-gas barrier thickness did not change with Ptm. At low Ptm, interstitial thickness was greater than previously found in rabbits but not in dogs. We conclude that the Ptm required to cause stress failure of pulmonary capillaries is between 75 and 100 mmHg and is greater in Thoroughbred horses than in both rabbits and dogs.
Animals↗
High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma.
Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH2O positive end-expiratory pressure (PEEP) on one lung and 1-cmH2O PEEP on the other (High-PEEP group), or with 2-cmH2O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for alpha1(III) and alpha2(IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor-beta1. In contrast, alpha2(I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma.
Animals↗