Mineral distribution in rat skeletons after exposure to a microgravity model

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days show non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These findings are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.     

Gas exchange and intrapulmonary distribution of ventilation during continuous-flow ventilation

In 12 anesthetized paralyzed dogs, pulmonary gas exchange and intrapulmonary inspired gas distribution were compared between continuous-flow ventilation (CFV) and conventional mechanical ventilation (CMV). Nine dogs were studied while they were lying supine, and three dogs were studied while they were lying prone. A single-lumen catheter for tracheal insufflation and a double-lumen catheter for bilateral endobronchial insufflation [inspired O2 fraction = 0.4; inspired minute ventilation = 1.7 +/- 0.3 (SD) 1.kg-1.min-1] were evaluated. Intrapulmonary gas distribution was assessed from regional 133Xe clearances. In dogs lying supine, CO2 elimination was more efficient with endobronchial insufflation than with tracheal insufflation, but the alveolar-arterial O2 partial pressure difference was larger during CFV than during CMV, regardless of the type of insufflation. By contrast, endobronchial insufflation maintained both arterial PCO2 and alveolar-arterial O2 partial pressure difference at significantly lower levels in dogs lying prone than in dogs lying supine. In dogs lying supine, the dependent lung was preferentially ventilated during CMV but not during CFV. In dogs lying prone, gas distribution was uniform with both modes of ventilation. The alveolar-arterial O2 partial pressure difference during CFV in dogs lying supine was negatively correlated with the reduced ventilation of the dependent lung, which suggests that increased ventilation-perfusion mismatching was responsible for the increase in alveolar-arterial O2 partial pressure difference. The more efficient oxygenation during CFV in dogs lying prone suggests a more efficient matching of ventilation to perfusion, presumably because the distribution of blood flow is also nearly uniform.     

Effect of lung volume on ventilation distribution

To examine the effect of preinspiratory lung volume (PILV) on ventilation distribution, we performed multiple-breath N2 washouts (MBNW) in seven normal subjects breathing 1-liter tidal volumes over a wide range of PILV above closing capacity. We measured the following two independent indexes of ventilation distribution from the MBNW: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency during that portion of the washout where 80-90% of the lung N2 had been cleared. Three of the subjects also performed single-breath N2 washouts (SBNW) by inspiring 1-liter breaths and expiring to residual volume at PILV = functional residual capacity (FRC), FRC + 1.0, and FRC - 0.5, respectively. From the SBNW we measured the phase III slope over the expired volume ranges of 0.75-1.0, 1.0-1.6, and 1.6-2.2 liters (S0.75, S1.0, and S1.6, respectively). Between a PILV of 0.92 +/- 0.09 (SE) liter above FRC and a PILV of 1.17 +/- 0.43 liter below FRC, Snf decreased by 61% (P less than 0.001) and alveolar mixing efficiency increased from 80 to 85% (P = 0.05). In addition, Snf and alveolar mixing efficiency were negatively correlated (r = 0.74). In contrast, over a similar volume range, S1.0 and S1.6 were greater at lower PILV. We conclude that, during tidal breathing in normal subjects, ventilation distribution becomes progressively more inhomogeneous at higher lung volumes over a range of volumes above closing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of airway closure on ventilation distribution

We examined the effect of airway closure on ventilation distribution during tidal breathing in six normal subjects. Each subject performed multiple-breath N2 washouts (MBNW) at tidal volumes of 1 liter over a range of preinspiratory lung volumes (PILV) from functional residual capacity (FRC) to just above residual volume. All subjects performed washouts at PILV below their measured closing capacity. In addition five of the subjects performed MBNW at PILV below closing capacity with end-inspiratory breath holds of 2 or 5 s. We measured the following two independent indexes of ventilation maldistribution: 1) the normalized phase III slope of the final breaths of the washout (Snf) and 2) the alveolar mixing efficiency of those breaths of the washout where 80-90% of the initial N2 had been cleared. Between a mean PILV of 0.28 liter above closing capacity and that 0.31 liter below closing capacity, mean Snf increased by 132% (P less than 0.005). Over the same volume range, mean alveolar mixing efficiency decreased by 3.3% (P less than 0.05). Breath holding at PILV below closing capacity resulted in marked and consistent decreases in Snf and increases in alveolar mixing efficiency. Whereas inhomogeneity of ventilation decreases with lung volume when all airways are patent (J. Appl. Physiol. 66: 2502-2510, 1989), airway closure increases ventilation inequality, and this is substantially reduced by short end-inspiratory breath holds. These findings suggest that the predominant determinant of ventilation distribution below closing capacity is the inhomogeneous closure of airways subtending regions in the lung periphery that are close together.     

Fractal nature of regional ventilation distribution.

High-resolution measurements of pulmonary perfusion reveal substantial spatial heterogeneity that is fractally distributed. This observation led to the hypothesis that the vascular tree is the principal determinant of regional blood flow. Recent studies using aerosol deposition show similar ventilation heterogeneity that is closely correlated with perfusion. We hypothesize that ventilation has fractal characteristics similar to blood flow. We measured regional ventilation and perfusion with aerosolized and injected fluorescent microspheres in six anesthetized, mechanically ventilated pigs in both prone and supine postures. Adjacent regions were clustered into progressively larger groups. Coefficients of variation were calculated for each cluster size to determine fractal dimensions. At the smallest size lung piece, local ventilation and perfusion are highly correlated, with no significant difference between ventilation and perfusion heterogeneity. On average, the fractal dimension of ventilation is 1.16 in the prone posture and 1. 09 in the supine posture. Ventilation has fractal properties similar to perfusion. Efficient gas exchange is preserved, despite ventilation and perfusion heterogeneity, through close correlation. One potential explanation is the similar geometry of bronchial and vascular structures.     

Physiology in microgravity.

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.     

Otoliths developed in microgravity

Little is known about mechanisms that regulate the development of the otoliths in the gravity-sensing organs. Several reported experiments suggest that the growth of the otoliths is adjusted to produce a test mass of the appropriate weight. If this is the case, larger than normal otoliths would be expected in animals reared in reduced gravity and a reduced mass, relative to 1-g controls, would be expected in animals reared at elevated g. In gastropod mollusks, the gravity-sensing organ is the statocyst, a spherical organ whose wall is made largely of sensory receptor cells with motile cilia facing the lumen. Dense statoconia in the cyst lumen interact with cilia of receptor cells at the bottom of the cyst and action potentials in their axons carry information on direction and magnitude of gravity and linear acceleration. In the marine mollusk, Aplysia californica, larvae reared at 2 to 5-g, the volume of statoconia was reduced in a graded manner, compared to 1-g control animals. In the statocyst of the fresh-water pond snail, Biomphalaria glabrata, reared in space in the Closed Equilibrated Biological Aquatic System (CEBAS), the number and total volume of statoconia was increased approximately 50%, relative to ground-reared controls. Lychakov found the utricular otolith to be 30% larger in space-reared Xenopus, whereas we found the saccular otolith to be significantly larger in newt larvae reared in space. In cichlid fish reared on a centrifuge, the saccular otolith was smaller than in 1-g controls. Here, we demonstrate that the otoliths of late-stage embryos of the swordtail fish, Xiphophorus helleri, reared in space on STS-89 and STS-90 (Neurolab) were significantly larger than those of ground-controls reared in functionally identical hardware.     

Pulmonary blood flow distribution during partial liquid ventilation

Regionalpulmonary blood flow was investigated with radiolabeled microspheres infour supine lambs during the transition from conventional mechanicalventilation (CMV) to partial liquid ventilation (PLV) and withincremental dosing of perfluorocarbon liquid to a cumulative dose of 30 ml/kg. Four lambs supported with CMV served as controls.Formalin-fixed, air-dried lungs were sectioned according to a grid;activity was quantitated with a multichannel scintillation counter,corrected for weight, and normalized to mean flow. During CMV, flow inapical and hilar regions favored dependent lung(P < 0.001), with no gradient acrosstransverse planes from apex to diaphragm. During PLV the gradientwithin transverse planes found during CMV reversed, most notably in thehilar region, favoring nondependent lung(P = 0.03). Also during PLV, flow wasprofoundly reduced near the diaphragm(P < 0.001), and across transverse planes from apex to diaphragm a dose-augmented flow gradient developed favoring apical lung (P < 0.01). Weconclude that regional flow patterns during PLV partially reverse thosenoted during CMV and vary dramatically within the lung from apex todiaphragm.