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G Kim Prisk

Publications and source records attributed to G Kim Prisk.

18 recordsLinked to original sources

Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.

Adult↗

Vital capacity, respiratory muscle strength, and pulmonary gas exchange during long-duration exposure to microgravity.

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.

Adult↗

Aerosols in the study of convective acinar mixing.

Convective mixing (CM) refers to the different transport mechanisms except Brownian diffusion that irreversibly transfer inspired air into resident air and can be studied using aerosol bolus inhalations. This paper provides a review of the present understanding of how each of these mechanisms contributes to CM. Original data of the combined effect of stretch and fold and gravitational sedimentation on CM are also presented. Boli of 0.5 microm-diameter particles were inhaled at penetration volumes (V(p)) of 300 and 1200 ml in eight subjects. Inspiration was followed by a 10-s breath hold, during which small flow reversals (FR) were imposed, and expiration. There was no physiologically significant dependence in dispersion and deposition with increasing FR. The results were qualitatively similar to those obtained in a previous study in microgravity in which it was speculated that the phenomenon of stretch and fold occurred during the first breathing cycle without the need of any subsequent FR.

Adult↗

Airway closure in microgravity.

Recent single breath washout (SBW) studies in microgravity and on the ground have suggested an important effect of airway closure on gas mixing in the human lung, reflected particularly in the phase III slope of vital capacity SBW and bolus tests. In order to explore this effect, we designed a SBW in which subjects inspired 2-l from residual volume (RV) starting with a 150 ml bolus of He and SF6. In an attempt to vary the pattern of airways closure configuration before the test, the experiments were conducted in 1G and in microgravity during parabolic flight allowing the pre-test expiration to RV to be either in microgravity or at 1.8 G, with the actual test gas inhalation performed entirely in microgravity. Contrary to our expectations, the measured phase III slope and phase IV height and volume obtained from seven subjects in microgravity were essentially identical irrespective of the gravity level during the pre-test expiration to RV. The results suggest that airway closure configuration at RV before the test inspiration has no apparent impact on phases III and IV generation.

Closing Volume↗

Foreword.

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Animals↗

Pulmonary gas exchange is not impaired 24 h after extravehicular activity.

Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung.

Adaptation, Physiological↗

Inhomogeneity of ventilation leads to unpredictable errors in measured D(L)CO.

We evaluated the effects of inhomogeneity of ventilation on single-breath (SB), rebreathing (RB) and open circuit (OC) D(L)CO using a mathematical model consisting of two alveolar compartments and a common dead space. Inhomogeneity in ventilation was studied by altering inspired volume, initial alveolar volume and compartment size independently. When distribution of inspired volume between alveolar compartments was inhomogeneous (9:1), D(L)CO was underestimated by 35% for SB, 25% for RB, and 16% for OC, and there was an underestimation in V(A) of 9%, 15% and 9%, respectively. With inhomogeneity in initial alveolar volume there was an overestimation in D(L)CO of 13%, 7% and 11% for SB, RB and OC techniques and an underestimation of V(A) of 7%, 12% and 9%. Finally inhomogeneity of compartment size led to an underestimation of D(L)CO of 18%, 35% and 36% with no change in measured V(A). These results suggest D(L)CO measurements are sensitive to inhomogeneity of ventilation, and importantly, all techniques were at times, significantly in error.

Algorithms↗

The lung in space.

The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

Exercise↗

Effect of small flow reversals on aerosol mixing in the alveolar region of the human lung.

It has been suggested that irreversibility of alveolar flow combined with a stretched and folded pattern of streamlines can lead to a sudden increase in mixing in the lung. To determine whether this phenomenon is operative in the human lung in vivo, we performed a series of bolus studies with a protocol designed to induce complex folding patterns. Boli of 0.5- and 1-microm-diameter particles were inhaled at penetration volumes (V(p)) of 300 and 1,200 ml in eight subjects during short periods of microgravity aboard the National Aeronautics and Space Administration Microgravity Research Aircraft. Inspiration was from residual volume to 1 liter above 1 G functional residual capacity. This was followed by a 10-s breathhold, during which up to seven 100-ml flow reversals (FR) were imposed at V(p) = 300 ml and up to four 500-ml FR at V(p) = 1,200 ml, and by an expiration to residual volume. Bolus dispersion and deposition were calculated from aerosol concentration and flow rate continuously monitored at the mouth. There was no significant increase in dispersion and deposition with increasing FR except for dispersion between 0 and 7 FR at V(p) = 300 ml with 0.5-microm-diameter particles, and this increase was small. This suggested that either the phenomenon of stretch and fold did not occur within the number of FR we performed or that it had already occurred during the one breathing cycle included in the basic maneuver. We speculate that the phenomenon occurred during the basic maneuver, which is consistent with the high degree of dispersion and deposition observed previously in microgravity.

Adult↗

Effect of 60 degrees head-down tilt on peripheral gas mixing in the human lung.

The phase III slope of sulfur hexafluoride (SF6) in a single-breath washout (SBW) is greater than that of helium (He) under normal gravity (i.e., 1G), thus resulting in a positive SF6-He slope difference. In microgravity (microG), SF6-He slope difference is smaller because of a greater fall in the phase III slope of SF6 than He. We sought to determine whether increasing thoracic fluid volume using 60 degrees head-down tilt (HDT) in 1G would produce a similar effect to microG on phase III slopes of SF6 and He. Single-breath vital capacity (SBW) and multiple-breath washout (MBW) tests were performed before, during, and 60 min after 1 h of HDT. Compared with baseline (SF6 1.050 +/- 0.182%/l, He 0.670 +/- 0.172%/l), the SBW phase III slopes for both SF6 and He tended to decrease during HDT, reaching nadir at 30 min (SF6 0.609 +/- 0.211%/l, He 0.248 +/- 0.138%/l; P = 0.08 and P = 0.06, respectively). In contrast to microG, the magnitude of the phase III slope decrease was similar for both SF6 and He; therefore, no change in SF6-He slope difference was observed. MBW analysis revealed a decrease in normalized phase III slopes at all time points during HDT, for both SF6 (P < 0.01) and He (P < 0.01). This decrease was due to changes in the acinar, and not the conductive, component of the normalized phase III slope. These findings support the notion that changes in thoracic fluid volume alter ventilation distribution in the lung periphery but also demonstrate that the effect during HDT does not wholly mimic that observed in microG.

Adaptation, Physiological↗

Aerosol deposition in the human respiratory tract breathing air and 80:20 heliox.

Aerosol mixing resulting from turbulent flows is thought to be an important mechanism of deposition in the upper respiratory tract (URT). Since turbulence levels are a function of gas density, the use of a low density carrier gas would be expected to reduce deposition in the URT. We measured aerosol deposition in the respiratory tract of 8 healthy subjects using both air and heliox, a low density gas mixture containing 80% helium and 20% oxygen, as the carrier gas. The subjects breathed 0.5, 1, and 2 microm-diameter monodisperse polystyrene latex particles from a reservoir at a constant flow rate (approximately 450 mL/sec) and tidal volume (approximately 900 mL). Aerosol concentration and flow rate were measured at the mouth using a photometer and a pneumotachograph, respectively. Deposition was 17.0%, 20.3%, and 38.9% in air and 16.8%, 18.5%, and 36.9% in heliox for 0.5; 1, and 2 microm-diameter particles, respectively. There was a small but statistically significant decrease in deposition when using heliox compared to air for 1 and 2 microm-diameter particles (p < 0.05). While it could not be directly measured from these data, it is likely that when breathing heliox instead of air, deposition is reduced in the URT and increased in the small airways and alveoli.

Adult↗

Microgravity alters respiratory sinus arrhythmia and short-term heart rate variability in humans.

We studied heart rate (HR), heart rate variability (HRV), and respiratory sinus arrhythmia (RSA) in four male subjects before, during, and after 16 days of spaceflight. The electrocardiogram and respiration were recorded during two periods of 4 min controlled breathing at 7.5 and 15 breaths/min in standing and supine postures on the ground and in microgravity. Low (LF)- and high (HF)-frequency components of the short-term HRV (< or =3 min) were computed through Fourier spectral analysis of the R-R intervals. Early in microgravity, HR was decreased compared with both standing and supine positions and had returned to the supine value by the end of the flight. In microgravity, overall variability, the LF-to-HF ratio, and RSA amplitude and phase were similar to preflight supine values. Immediately postflight, HR increased by approximately 15% and remained elevated 15 days after landing. LF/HF was increased, suggesting an increased sympathetic control of HR standing. The overall variability and RSA amplitude in supine decreased postflight, suggesting that vagal tone decreased, which coupled with the decrease in RSA phase shift suggests that this was the result of an adaptation of autonomic control of HR to microgravity. In addition, these alterations persisted for at least 15 days after return to normal gravity (1G).

Adult↗

Effect of gravitational sedimentation on simulated aerosol dispersion in the human acinus.

We studied the effect of gravitational sedimentation on the dispersion of 0.5 and 1 micrometer-diameter particle boluses within a two-dimensional symmetric six-generation model of the human acinus. Boluses were introduced at the beginning of a 2-s inspiration immediately followed by a 4-s expiration, in normal gravity (1 G) and in the absence of gravity (0 G). The flow corresponded to a flow rate at the mouth of 500 ml/s. In 0 G, simulated dispersion (Hsim) was 16 ml for both particle sizes. In 1 G, Hsim was 71 and 242 ml for 0.5 and 1 micrometer-diameter particles, respectively, showing the effect of gravitational sedimentation. The difference between experimental data (J. Appl. Physiol. 86 (1999) 1402) and simulations was independent of particle size. This suggests that the residual dispersion was independent of the intrinsic properties of the particles and was more likely due to other mechanisms such as ventilation inhomogeneities, cardiogenic oscillations and alveolar wall motion.

Aerosols↗

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.

Algorithms↗

Tidal volume single-breath washin of SF6 and CH4 in transient microgravity.

We performed tidal volume single-breath washins (SBW) by using tracers of different diffusivity and varied the time spent in microgravity (microG) before the start of the tests to look for time-dependent effects. SF(6) and CH(4) phase III slopes decreased by 35 and 26%, respectively, in microG compared with 1 G (P < 0.05), and the slope difference between gases disappeared. There was no effect of time in microG, suggesting that neither the hypergravity period preceding microG nor the time spent in microG affected gas mixing at volumes near functional residual capacity. In previous studies using SF(6) and He (Lauzon A-M, Prisk GK, Elliott AR, Verbanck S, Paiva M, and West JB. J Appl Physiol 82: 859-865, 1997), the vital capacity SBW showed an increase in slope difference between gases in transient microG, the opposite of the decrease in sustained microG. In contrast, tidal volume SBW showed a decrease in slope difference in both microG conditions. Because it is only the behavior of the more diffusive gas that differed between maneuvers and microG conditions, we speculate that, in the previous vital capacity SBW, the hypergravity period preceding the test in transient microG provoked conformational changes at low lung volumes near the acinar entrance.

Adult↗

Techniques for measurement of thoracoabdominal asynchrony.

Respiratory motion measured by respiratory inductance plethysmography often deviates from the sinusoidal pattern assumed in the traditional Lissajous figure (loop) analysis used to determine thoraco-abdominal asynchrony, or phase angle phi. We investigated six different time-domain methods of measuring phi, using simulated data with sinusoidal and triangular waveforms, phase shifts of 0-135 degrees, and 10% noise. The techniques were then used on data from 11 lightly anesthetized rhesus monkeys (Macaca mulatta; 7.6 +/- 0.8 kg; 5.7 +/- 0.5 years old), instrumented with a respiratory inductive plethysmograph, and subjected to increasing levels of inspiratory resistive loading ranging from 5-1,000 cmH(2)O. L(-1). sec(-1). The best results were obtained from cross-correlation and maximum linear correlation, with errors less than approximately 5 degrees from the actual phase angle in the simulated data. The worst performance was produced by the loop analysis, which in some cases was in error by more than 30 degrees. Compared to correlation, other analysis techniques performed at an intermediate level. Maximum linear correlation and cross-correlation produced similar results on the data collected from monkeys (SD of the difference, 4.1 degrees ) but all other techniques had a high SD of the difference compared to the correlation techniques. We conclude that phase angles are best measured using cross-correlation or maximum linear correlation, techniques that are independent of waveform shape, and robust in the presence of noise.

Airway Obstruction↗

Mode shift of an inhaled aerosol bolus is correlated with flow sequencing in the human lung.

We studied the effects on aerosol bolus inhalations of small changes in convective inhomogeneity induced by posture change from upright to supine in nine normal subjects. Vital capacity single-breath nitrogen washout tests were used to determine ventilatory inhomogeneity change between postures. Relative to upright, supine phase III slope was increased 33 +/- 11% (mean +/- SE, P < 0.05) and phase IV height increased 25 +/- 11% (P < 0.05), consistent with an increase in convective inhomogeneity likely due to increases in flow sequencing. Subjects also performed 0.5-microm-particle bolus inhalations to penetration volumes (V(p)) between 150 and 1,200 ml during a standardized inhalation from residual volume to 1 liter above upright functional residual capacity. Mode shift (MS) in supine posture was more mouthward than upright at all V(p), changing by 11.6 ml at V(p) = 150 ml (P < 0.05) and 38.4 ml at V(p) = 1,200 ml (P < 0.05). MS and phase III slope changes correlated positively at deeper V(p). Deposition did not change at any V(p), suggesting that deposition did not cause the MS change. We propose that the MS change results from increased sequencing in supine vs. upright posture.

Adult↗

Effect of 6 degrees head-down tilt on cardiopulmonary function: comparison with microgravity.

BACKGROUND: Head-down tilt (HDT) of 6 degrees is a commonly used model of weightlessness, but there are few comparisons with actual microgravity. HYPOTHESIS: Our study was designed to prove that the changes in cardiopulmonary function seen in HDT would be similar to those seen in microgravity. METHODS: We compared measurements of cardiovascular and pulmonary function from three separate spaceflights of 14 to 17 d duration, with data collected during a 17-d period of HDT. RESULTS: HDT proved a good model of the cardiovascular response to microgravity, resulting in increases in cardiac output and stroke volume of a similar magnitude to those seen in microgravity, with a concomitant reduction in heart rate. By contrast, HDT was a poor model of the effects of microgravity on pulmonary ventilation and gas exchange. CONCLUSION: Pulmonary function in HDT approximated the changes seen in the 1-G supine posture, while in microgravity this was much closer to that seen in the 1-G upright position. The differences probably reflect the fact that changes in cardiovascular function result primarily from fluid shifts within the entire body, whereas changes in pulmonary ventilation are primarily a result of mechanical influences on the lung and chest and abdominal wall.

Adult↗