Effects of oral sodium nitrate on forearm blood flow, oxygenation and exercise performance during acute exposure to hypobaric hypoxia (4300 m).

A reduction in oxygen transport contributes to impaired exercise capacity at high altitude. Since blood flow is mediated, in part, by nitric oxide (NO), we hypothesized that sodium nitrate provided before forearm grip exercise performed at a simulated altitude of 4300 m (hypobaric hypoxia (HH)) would increase forearm blood flow and oxygenation, and decrease the decrement in grip performance. In a double-blind, randomized crossover study, 10 healthy subjects (9 males and 1 female) performed continuous (CGrip) and repeated rhythmic (RGrip) isometric forearm exercise until task failure in normobaric normoxia (NN), 2.5 h following consumption of placebo and sodium nitrate (15 mmol) in HH, and then again post-HH at sea-level pressure. Measurements included forearm blood flow (FBF) and anterior forearm tissue oxygenation (StO2), mean arterial blood pressure (MAP), arterial blood O2 saturation (SpO2), plasma NO reaction products (NOx) and nitrite, and exhaled NO (PENO). Compared to baseline testing in NN, performing CGrip and RGrip exercise in HH resulted in significant reductions in forearm blood flow, SaO2 and StO2, responses that were accompanied by significant performance decrements (∼10%) in both CGrip and RGrip exercise. In spite of a 10-fold increase in plasma NOx levels and a significant decrease in MAP during CGrip exercise following nitrate consumption, there were no significant main effects of treatment (placebo vs. sodium nitrate) for forearm blood flow, SpO2, StO2, or grip performance. PENO remained unchanged between NN, HH and post-HH conditions with placebo, but increased (∼24%) following nitrate supplementation in HH and post-HH. These data do not support a benefit in consuming a single dose of supplemental nitrate on forearm blood flow and isometric exercise in healthy adults at a simulated altitude of 4300 m.

Oxygen breathing accelerates decompression from saturation at 40 msw in 70-kg swine.

INTRODUCTION: Submarine disaster survivors can be transferred from a disabled submarine at a pressure of 40 meters of seawater (msw) to a new rescue vehicle; however, they face an inherently risky surface interval before recompression and an enormous decompression obligation due to a high likelihood of saturation. The goal was to design a safe decompression protocol using oxygen breathing and a trial-and-error methodology. We hypothesized that depth, timing, and duration of oxygen breathing during decompression from saturation play a role to mitigate decompression outcomes. METHODS: Yorkshire swine (67-75 kg), compressed to 40 msw for 22 h, underwent one of three accelerated decompression profiles: (1) 13.3 h staged air decompression to 18 msw, followed by 1 h oxygen breathing, then dropout; (2) direct decompression to 18 msw followed by 1 h oxygen breathing then dropout; and (3) 1 h oxygen prebreathe at 40 msw followed by 1 h mixed gas breathing at 26 msw, 1 h oxygen breathing at 18 msw, and 1 h ascent breathing oxygen. Animals underwent 2-h observation for signs of DCS. RESULTS: Profile 1 (14.3 h total) resulted in no deaths, no Type II DCS, and 20% Type I DCS. Profile 2 (2.1 h total) resulted in 13% death, 50% Type II DCS, and 75% Type I DCS. Profile 3 (4.5 h total) resulted in 14% death, 21% Type II DCS, and 57% Type I DCS. No oxygen associated seizures occurred. DISCUSSION: Profile 1 performed best, shortening decompression with no death or severe DCS, yet it may still exceed emergency operational utility in an actual submarine rescue.

Comparison of postnatal lung growth and development between C3H/HeJ and C57BL/6J mice.

Previous work by our group has demonstrated substantial differences in lung volume and morphometric parameters between inbred mice. Specifically, adult C3H/HeJ (C3) have a 50% larger lung volume and 30% greater mean linear intercept than C57BL/6J (B6) mice. Although much of lung development occurs postnatally in rodents, it is uncertain at what age the differences between these strains become manifest. In this study, we performed quasi-static pressure-volume curves and morphometric analysis on neonatal mice. Lungs from anesthetized mice were degassed in vivo using absorption of 100% O2. Pressure-volume curves were then recorded in situ. The lungs were then fixed by instillation of Zenker's solution at a constant transpulmonary pressure. The left lung from each animal was used for morphometric determination of mean air space chord length (Lma). We found that the lung volume of C3 mice was substantially greater than that of B6 mice at all ages. In contrast, there was no difference in Lma (62.7 microm in C3 and 58.5 microm in B6) of 3-day-old mice. With increasing age (8 days), there was a progressive decrease in the Lma of both strains, with the magnitude of the decrease in B6 Lma mice exceeding that of C3. C3 lung volume remained 50% larger. The combination of parenchymal architectural similarity with lung air volume differences and different rates of alveolar septation support the hypothesis that lung volume and alveolar dimensions are independently regulated.

At-sea trial of 24-h-based submarine watchstanding schedules with high and low correlated color temperature light sources.

United States Navy submariners have historically lived with circadian disruption while at sea due to 18-h-based watchschedules. Previous research demonstrated that circadian entrainment improved with 24-h-based watchschedules. Twenty-nine male crew members participated in the study, which took place on an actual submarine patrol. The crew were exposed, first, to experimental high correlated color temperature (CCT = 13,500 K) fluorescent light sources and then to standard-issue fluorescent light sources (CCT = 4100 K). A variety of outcome measures were employed to determine if higher levels of circadian-effective light during on-watch times would further promote behavioral alignment to 24-h-based watchschedules. The high CCT light source produced significantly higher circadian light exposures than the low CCT light source, which was associated with significantly greater 24-h behavioral alignment with work schedules using phasor analysis, greater levels of sleep efficiency measured with wrist actigraphy, lower levels of subjective sleepiness measured with the Karolinska Sleepiness Scale, and higher nighttime melatonin concentrations measured by morning urinary 6-sulfatoxymelatonin/creatinine ratios. Unlike these diverse outcome measures, performance scores were significantly worse under the high CCT light source than under the low CCT light source, due to practice effects. As hypothesized, with the exception of the performance scores, all of the data converge to suggest that high CCT light sources, combined with 24-h watchschedules, promote better behavioral alignment with work schedules and greater sleep quality on submarines. Since the order and the type of light sources were confounded in this field study, the results should only be considered as consistent with our theoretical understanding of how regular, 24-h light-dark exposures combined with high circadian light exposures can promote greater behavioral alignment with work schedules and with sleep.

On defining total lung capacity in the mouse.

Maximal lung volume or total lung capacity in experimental animals is dependent on the pressure to which the lungs are inflated. Although 25-30 cm H2O are nominally used for such inflations, mouse pressure-volume (P-V) curves show little flattening on inflation to those pressures. In the present study, we examined P-V relations and mean alveolar chord length in three strains (C3H/HeJ, A/J, and C57BL/6J) at multiple inflation pressures. Mice were anesthetized, and their lungs were degassed in vivo by absorption of 100% O2. P-V curves were then recorded in situ with increasing peak inflation pressure in 10-cm H2O increments up to 90 cm H2O. Lungs were quickly frozen at specific pressures for morphometric analysis. The inflation limbs never showed the appearance of a plateau, with lung volume increasing 40-60% as inflation pressure was increased from 30 to 60 cm H2O. In contrast, parallel flat deflation limbs were always observed, regardless of the inflation pressure, indicating that the presence of a flat deflation curve cannot be used to justify measurement of total lung capacity in mice. Alveolar size increased monotonically with increasing pressure in all strains, and there was no evidence of irreversible lung damage from these inflations to high pressures. These results suggest that the mouse lung never reaches a maximal volume, even up to nonphysiological pressures >80 cm H2O.

Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice.

Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly (P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant (P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.

Differences in alveolar size in inbred mouse strains.

In this paper we examined structural differences in alveolar size among inbred mouse strains which are known to have significant differences in lung pressure-volume relations. Accordingly, we assessed whether the relative size or number of alveoli in the C3H/HeJ, C57BL/6J, and A/J strains are related to these lung volume differences. Lungs from each of these strains were fixed in situ and then excised for quantitative morphometric analysis of airspace chord lengths. Mean chord lengths (in microm) were significantly different (P < 0.0001) among the three strains, with the largest alveoli found in the C3H/HeJ mice (45 +/- 5), the smallest in the C57BL/6J mice (35 +/- 3), and intermediate in the A/J strain (38 +/- 2). These findings provide clear evidence that there are significant genetic differences in the lung structure among different mouse strains. However, since the A/J and C57BL/6J mice had similar lung volumes, there does not yet seem to be a clear link between the macroscopic manifestations of the microscopic structure. We speculate that these structural differences might have significant influence on several mouse models of lung disease, especially those involving the development of emphysema.