Pulmonary Deposition of Aerosols in Microgravity

The intrapulmonary deposition of airborne particles (aerosol) in the size range of 0.5 to 5 microns is primarily due to gravitational sedimentation. In the microgravity (muG) environment, sedimentation is no longer active, and thus there should be marked changes in the amount and site of the deposition of these aerosol. We propose to study the total intrapulmonary deposition of aerosol spanning the range 0.5 to 5 microns in the KC-135 at both muG and at 1.8-G. This will be followed by using boli of 1.0 micron aerosol, inhaled at different points in a breath to study aerosol dispersion and deposition as a function of inspired depth. The results of these studies will have application in better understanding of pulmonary diseases related to inhaled particles (pneumoconioses), in studying drugs delivered by inhalation, and in understanding the consequence of long-term exposure to respirable aerosols in long-duration space flight

A Simulated Microgravity Environment Causes a Sustained Defect in Epithelial Barrier Function.

Intestinal epithelial cell (IEC) junctions constitute a robust barrier to invasion by viruses, bacteria and exposure to ingested agents. Previous studies showed that microgravity compromises the human immune system and increases enteropathogen virulence. However, the effects of microgravity on epithelial barrier function are poorly understood. The aims of this study were to identify if simulated microgravity alters intestinal epithelial barrier function (permeability), and susceptibility to barrier-disrupting agents. IECs (HT-29.cl19a) were cultured on microcarrier beads in simulated microgravity using a rotating wall vessel (RWV) for 18 days prior to seeding on semipermeable supports to measure ion flux (transepithelial electrical resistance (TER)) and FITC-dextran (FD4) permeability over 14 days. RWV cells showed delayed apical junction localization of the tight junction proteins, occludin and ZO-1. The alcohol metabolite, acetaldehyde, significantly decreased TER and reduced junctional ZO-1 localization, while increasing FD4 permeability in RWV cells compared with static, motion and flask control cells. In conclusion, simulated microgravity induced an underlying and sustained susceptibility to epithelial barrier disruption upon removal from the microgravity environment. This has implications for gastrointestinal homeostasis of astronauts in space, as well as their capability to withstand the effects of agents that compromise intestinal epithelial barrier function following return to Earth

In silico modeling of oxygen-enhanced MRI of specific ventilation.

Specific ventilation imaging (SVI) proposes that using oxygen-enhanced 1H MRI to capture signal change as subjects alternatively breathe room air and 100% O2 provides an estimate of specific ventilation distribution in the lung. How well this technique measures SV and the effect of currently adopted approaches of the technique on resulting SV measurement is open for further exploration. We investigated (1) How well does imaging a single sagittal lung slice represent whole lung SV? (2) What is the influence of pulmonary venous blood on the measured MRI signal and resultant SVI measure? and (3) How does inclusion of misaligned images affect SVI measurement? In this study, we utilized two patient-based in silico models of ventilation, perfusion, and gas exchange to address these questions for normal healthy lungs. Simulation results from the two healthy young subjects show that imaging a single slice is generally representative of whole lung SV distribution, with a calculated SV gradient within 90% of that calculated for whole lung distributions. Contribution of O2 from the venous circulation results in overestimation of SV at a regional level where major pulmonary veins cross the imaging plane, resulting in a 10% increase in SV gradient for the imaging slice. A worst-case scenario simulation of image misalignment increased the SV gradient by 11.4% for the imaged slice

Ventilation–perfusion heterogeneity measured by the multiple inert gas elimination technique is minimally affected by intermittent breathing of 100% O2

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion ((Formula presented.)) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2-dependent manner. Specific ventilation imaging data are acquired during five wash-in/wash-out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect (Formula presented.) heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases (Formula presented.) mismatch in nine patients with abnormal pulmonary gas exchange and increased (Formula presented.) mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated-SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus (Formula presented.) ratio, LogSD (Formula presented.), and perfusion versus (Formula presented.) ratio, LogSD (Formula presented.) were calculated. LogSD (Formula presented.) was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p =.84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p =.04). There was no significant difference in LogSD (Formula presented.) across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p =.54); Deadspace was not significantly different (p =.54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p =.052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter (Formula presented.) matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized

Ventilation-perfusion inequality in the human lung is not increased following no-decompression-stop hyperbaric exposure

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects within the pulmonary circulation. Two sets of healthy volunteers (n = 11, n = 12) were recruited to test this hypothesis with a single recreational ocean dive or a baro-equivalent dry hyperbaric dive. Pulmonary studies (intrabreath VA/Q (iV/Q), alveolar dead space, and FVC) were conducted at baseline and repeat 1- and 24-h after the exposure. Contrary to our hypothesis VA/Q mismatch was decreased 1-h post-SCUBA dive (iV/Q slope 0.023 ± 0.008 ml−1 at baseline vs. 0.010 ± 0.005 NS), and was significantly reduced 24-h post-SCUBA dive (0.000 ± 0.005, p < 0.05), with improved VA/Q homogeneity inversely correlated to dive severity. No changes in VA/Q mismatch were observed after the chamber dive. Alveolar dead space decreased 24-h post-SCUBA dive (78 ± 10 ml at baseline vs. 56 ± 5, p < 0.05), but not 1-h post dive. FVC rose 1-h post-SCUBA dive (5.01 ± 0.18 l vs. 5.21 ± 0.26, p < 0.05), remained elevated 24-h post SCUBA dive (5.06 ± 0.2, p < 0.05), but was decreased 1-hr after the chamber dive (4.96 ± 0.31 L to 4.87 ± 0.32, p < 0.05). The degree of VA/Q mismatch in the lung was decreased following recreational ocean dives, and was unchanged following an equivalent air chamber dive, arguing against an impact of VGE on the pulmonary circulation

A Method for the Analysis of Respiratory Sinus Arrhythmia Using Continuous Wavelet Transforms

Abstract-A continuous wavelet transform-based method is presented to study the nonstationary strength and phase delay of the respiratory sinus arrhythmia (RSA). The RSA is the cyclic variation of instantaneous heart rate at the breathing frequency. In studies of cardio-respiratory interaction during sleep, paced breathing or postural changes, low respiratory frequencies, and fast changes can occur. Comparison on synthetic data presented here shows that the proposed method outperforms traditional short-time Fourier-transform analysis in these conditions. On the one hand, wavelet analysis presents a sufficient frequency-resolution to handle low respiratory frequencies, for which time frames should be long in Fourier-based analysis. On the other hand, it is able to track fast variations of the signals in both amplitude and phase for which time frames should be short in Fourier-based analysis. Index Terms-Cardio-respiratory interaction, continuous wavelet transform (CWT), heart rate variability (HRV), respiratory sinus arrhythmia (RSA)

Toxicity of lunar dust

The formation, composition and physical properties of lunar dust are incompletely characterised with regard to human health. While the physical and chemical determinants of dust toxicity for materials such as asbestos, quartz, volcanic ashes and urban particulate matter have been the focus of substantial research efforts, lunar dust properties, and therefore lunar dust toxicity may differ substantially. In this contribution, past and ongoing work on dust toxicity is reviewed, and major knowledge gaps that prevent an accurate assessment of lunar dust toxicity are identified. Finally, a range of studies using ground-based, low-gravity, and in situ measurements is recommended to address the identified knowledge gaps. Because none of the curated lunar samples exist in a pristine state that preserves the surface reactive chemical aspects thought to be present on the lunar surface, studies using this material carry with them considerable uncertainty in terms of fidelity. As a consequence, in situ data on lunar dust properties will be required to provide ground truth for ground-based studies quantifying the toxicity of dust exposure and the associated health risks during future manned lunar missions.Comment: 62 pages, 9 figures, 2 tables, accepted for publication in Planetary and Space Scienc

A Model Analysis of Arterial Oxygen Desaturation during Apnea in Preterm Infants

Rapid arterial O2 desaturation during apnea in the preterm infant has obvious clinical implications but to date no adequate explanation for why it exists. Understanding the factors influencing the rate of arterial O2 desaturation during apnea () is complicated by the non-linear O2 dissociation curve, falling pulmonary O2 uptake, and by the fact that O2 desaturation is biphasic, exhibiting a rapid phase (stage 1) followed by a slower phase when severe desaturation develops (stage 2). Using a mathematical model incorporating pulmonary uptake dynamics, we found that elevated metabolic O2 consumption accelerates throughout the entire desaturation process. By contrast, the remaining factors have a restricted temporal influence: low pre-apneic alveolar causes an early onset of desaturation, but thereafter has little impact; reduced lung volume, hemoglobin content or cardiac output, accelerates during stage 1, and finally, total blood O2 capacity (blood volume and hemoglobin content) alone determines during stage 2. Preterm infants with elevated metabolic rate, respiratory depression, low lung volume, impaired cardiac reserve, anemia, or hypovolemia, are at risk for rapid and profound apneic hypoxemia. Our insights provide a basic physiological framework that may guide clinical interpretation and design of interventions for preventing sudden apneic hypoxemia

Ventilation distribution

A major breakthrough in the understanding of the distribution of ventilation was achieved in 1966 with the publication of three papers using radioactive gas techniques to measure regional pulmonary ventilation (1-3). Not only were the measurements more reliable than lobar spirometry, but quantitative data could also be obtained on a topographical basis, corresponding to, for example, the vertical distance from the top to the bottom of the lung. Since then, most of the information on regional ventilation distribution has been obtained with radioactive gases. However, these techniques have never been used in space, and most of the experiments used to study microgravity effects on the lung are indirect techniques such as single-and multiple-breath inert gas washouts (4,5). Predictions were made of the results of the experiments performed in microgravity (obtained in space or in aircraft during parabolic trajectories), and from the differences between predictions and observations we gained insight into the behavior of inhaled gas in the human lung. In this chapter we present a number of examples where studies in microgravity have provided insight into the basic physiology.SCOPUS: ch.binfo:eu-repo/semantics/publishe