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We measured pulmonary diffusing capacity (DL), diffusing capacity per unit lung volume, pulmonary capillary blood volume (Vc), membrane diffusing capacity (Dm), pulmonary capillary blood flow or cardiac output (Qc), and cardiac stroke volume (SV) in four subjects exposed to 9 days of microgravity (weightlessness, 0 G). The same subjects were studied standing and supine numerous times preflight and in the week immediately after return from space. DL in microgravity was elevated (28%) compared with preflight standing values and was higher than preflight supine because of the elevation of both Vc (28%) and Dm (27%). The elevation in Vc was comparable to that measured supine in 1 G, but the increase in Dm was in sharp contrast to the supine value (which was unchanged). We postulate that, in 0 G, pulmonary capillary blood is evenly distributed throughout the lung, providing for uniform capillary filling, leading to an increase in the surface area available for diffusion. By contrast, in the supine 1-G state, the capillaries are less evenly filled, and although a similar increase in blood volume is observed, the corresponding increase in surface area does not occur. DL and its subdivisions showed no adaptive changes from the first measurement 24 h after the start of 0 G to 8 days later. Similarly, there were no trends in the postflight data, suggesting that the principal mechanism of these changes was gravitational. The increase in Dm suggests that subclinical pulmonary edema did not result from exposure to 0 G. Qc was modestly increased (18%) inflight and decreased (9%) post-flight compared with preflight standing. Compared with preflight standing, SV was increased 46% inflight and decreased 14% in the 1st wk postflight. There were temporal changes in Qc and SV during 0 G, with the highest values recorded at the first measurement, 24 h into the flight. The lowest values of Qc and SV occurred on the day of return.

Gravity is known to cause inhomogeneity of ventilation. Nongravitational factors are also recognized, but their relative contribution is not understood. We therefore studied ventilatory inhomogeneity during sustained microgravity during the 9-day flight of Spacelab SLS-1. All seven crew members performed single-breath nitrogen washouts. They inspired a vital capacity breath of 100% oxygen with a bolus of argon at the start of inspiration, and the inspiratory and expiratory flow rates were controlled at 0.5 l/s. Control measurements in normal gravity (1 G) were made pre- and postflight in the standing and supine position. Compared with the standing 1-G measurements, there was a marked decrease in ventilatory inhomogeneity during microgravity, as evidenced by the significant reductions in cardiogenic oscillations, slope of phase III, and height of phase IV for nitrogen and argon. However, argon phase IV volume was not reduced, and considerable ventilatory inhomogeneity remained. For example, the heights of the cardiogenic oscillations during microgravity for nitrogen and argon were 44 and 24%, respectively, of their values at 1 G, whereas the slopes of phase III for nitrogen and argon were 78 and 29%, respectively, of those at 1 G. The presence of a phase IV in microgravity is strong evidence that airway closure still occurs in the absence of gravity. The results were qualitatively similar to those found previously during short periods of 0 G in parabolic flight.

Simultaneous determination of the accuracy and precision of closed-circuit cardiac output rebreathing techniques. J Appl Physiol 103: [867][868][869][870][871][872][873][874] 2007. First published June 7, 2007; doi:10.1152/japplphysiol.01106.2006.-Foreign and soluble gas rebreathing methods are attractive for determining cardiac output (Q c) because they incur less risk than traditional invasive methods such as direct Fick and thermodilution. We compared simultaneously obtained Q c measurements during rest and exercise to assess the accuracy and precision of several rebreathing methods. Q c measurements were obtained during rest (supine and standing) and stationary cycling (submaximal and maximal) in 13 men and 1 woman (age: 24 Ϯ 7 yr; height: 178 Ϯ 5 cm; weight: 78 Ϯ 13 kg; V O2max: 45.1 Ϯ 9.4 ml⅐kg Ϫ1 ⅐min Ϫ1; mean Ϯ SD) using one-N 2O, four-C2H2, one-CO2 (single-step) rebreathing technique, and two criterion methods (direct Fick and thermodilution). CO 2 rebreathing overestimated Q c compared with the criterion methods (supine: 8.1 Ϯ 2.0 vs. 6.4 Ϯ 1.6 and 7.2 Ϯ 1.2 l/min, respectively; maximal exercise: 27.0 Ϯ 6.0 vs. 24.0 Ϯ 3.9 and 23.3 Ϯ 3.8 l/min). C 2H2 and N2O rebreathing techniques tended to underestimate Q c (range: 6.6 -7.3 l/min for supine rest; range: 16.0 -19.1 l/min for maximal exercise). Bartlett's test indicated variance heterogeneity among the methods (P Ͻ 0.05), where CO 2 rebreathing consistently demonstrated larger variance. At rest, most means from the noninvasive techniques were Ϯ10% of direct Fick and thermodilution. During exercise, all methods fell outside the Ϯ10% range, except for CO 2 rebreathing. Thus the CO2 rebreathing method was accurate over a wider range (rest through maximal exercise), but was less precise. We conclude that foreign gas rebreathing can provide reasonable Q c estimates with fewer repeat trials during resting conditions. During exercise, these methods remain precise but tend to underestimate Q c. Single-step CO 2 rebreathing may be successfully employed over a wider range but with more measurements needed to overcome the larger variability.foreign gas rebreathing; physiological gas rebreathing; direct Fick; thermodilution CARDIAC OUTPUT (Q c ), the volume of blood pumped by the heart each minute, can be measured several ways, both invasively and noninvasively. Each technique has advantages and limitations that may restrict its application during exercise. The direct Fick method has been implemented in humans in clinical environments since 1940 (21); together with the thermodilution method, they are considered "gold standard" Q c techniques. These methods, however, are expensive, require medical expertise, and are invasive, limiting their widespread utility (44). For instance, occasional reported complications associated with these gold standards include arrhythmias and pulmonary artery or right ventricle perforation (30, 40).Rebreathing techniques, employing foreign or physiological tracers, are attractive alternatives because their relative risk is considerably...

The toxic or therapeutic effect of an inhaled aerosol is highly dependent upon the site and extent of deposition in the lung. A novel MRI-based method was used to quantify the spatial distribution of particles in the rat lung. Rats were exposed to 0.95 μm-diameter iron oxide particles in a controlled manner (N=6) or to particle-free air (N=6). Lungs were fixed in 3 % glutaraldehyde by vascular perfusion, excised and imaged in a 3T scanner using a gradient-echo imaging protocol. The signal decay rate, R2∗, was measured in each voxel of the entire left lung (1 mm thick slices). R2∗ was significantly higher in exposed animals (0.0065 ± 0.0006 msec−1) than in controls (0.0050 ± 0.0003 msec−1, p<0.001). A calibration curve between R2∗ and concentration of deposited particles (Cpart) was obtained by imaging gel samples with known particle concentrations. Regional deposition was assessed by comparing Cpart between the outer (Cpart,peripheral) and inner (Cpart,central) areas on each transaxial slice, and expressed as the cp ratio. Cpart,peripheral (1.54 ± 0.70 μgml) was significantly, higher than Cpart,central ml (1.00 ± 0.39 μgml, p<0.05), resulting in a cp ratio of 0.65. This method may be used in future studies to quantify spatial distribution of deposited particles in healthy and diseased lungs.

Extended exposure to microgravity (microG) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short- duration exposure to microG reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O2 uptake, ventilation, or end-tidal partial pressures. Accordingly we measured VC, maximum inspiratory and expiratory pressures, and indexes of pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39-52 yr) who lived on the International Space Station for 130-196 days in a normoxic, normobaric atmosphere. Subjects were studied four times in the standing and supine postures preflight at sea level at 1 G, approximately monthly in microG, and multiple times postflight. VC in microG was essentially unchanged compared with preflight standing [5.28 +/- 0.08 liters (mean +/- SE), n = 187; 5.24 +/- 0.09, n = 117, respectively; P = 0.03] and considerably greater than that measured supine in 1G (4.96 +/- 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after the first 2 mo of microG, but there were no changes postflight. Maximum respiratory pressures in microG were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in microG. O2 uptake and CO2 production were reduced (approximately 12%) in extended microG, but inhomogeneity in the lung was not different compared with short-duration exposure to microG. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to microG, and metabolic rate is reduced.

Mass spectrometers produce distorted measurements of gas concentrations because of the time delays and rise times inherent in their responses. Three techniques for numerically correcting such distortion were applied to the acetylene step responses of a Perkin-Elmer MGA1100 mass spectrometer and to simulated data. The techniques investigated were 1) a simple time-delay correction, 2) an exponential model method that assumes a biexponential form for the peak of the impulse response, and 3) a Fourier transform method of deconvolution known as Wiener filtering. The time-delay correction produced an order of magnitude reduction in measurement error. The exponential model method improved on the time-delay correction, and the Wiener filter gave the most accurate corrections in all cases examined.

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.