[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Full-text · Article · Jul 2010 · Aviation Space and Environmental Medicine
[Show abstract][Hide abstract] ABSTRACT: Disabled submarine (DISSUB) survivors are expected to achieve saturation with inert gas. However, rescue procedures may not accommodate staged decompression, raising the potential for severe decompression sickness (DCS). Alternatives to standard recompression therapy are needed. It has been demonstrated in humans that isobaric oxygen "prebreathing" (OPB) can accelerate decompression in a DISSUB scenario. In-70 kg swine saturated at 2.82 atm absolute (ATA), 1 h of OPB eliminated death and reduced severe DCS. We hypothesized that even shorter periods (<1 h) of OPB before no-stop decompression from saturation at 2.82 ATA could reduce the incidence of DCS in a large animal model. Catheterized Yorkshire swine (68.8 +/- 1.7 kg) in individual Plexiglas boxes within a large animal hyperbaric chamber were compressed to 2.82 ATA for 22 h. Following saturation and while still at depth, breathing gas was switched to >95% O(2) for 45 min (OPB(45)), 15 min (OPB(15)), or 5 min (OPB(05)) of OPB, or no OPB (control). The chamber was then decompressed without stops (0.91 ATA/min). Observers then entered the chamber and recorded signs of DCS for 2 h. All OPB periods significantly reduced the risk of developing type II DCS. OPB(45) eliminated severe DCS. Controls had a 2.5 times greater risk of developing type II DCS than OPB(05) (P = 0.016). OPB(45) and OPB(15) significantly reduced type I DCS compared with controls. These results support the potential of OPB as an alternative to staged decompression and that OPB could be expected to improve outcome in a DISSUB rescue scenario.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jun 2006 · Journal of Applied Physiology
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Jun 2004 · Respiratory Physiology & Neurobiology
[Show abstract][Hide abstract] ABSTRACT: Hyperoxia is an important factor in the development of bronchopulmonary dysplasia and is associated with growth arrest and impaired alveolar septal development in the neonatal lung. p21(Waf1/Cip1/Sdi1) (p21), a cyclin-dependent kinase inhibitor, acts as a checkpoint regulator in the cell cycle during periods of stress and is induced in neonatal lung during hyperoxia exposure. To determine if p21 protects against lung injury during neonatal lung development, we placed newborn p21 knockout (p21(-/-)) and p21 wild-type (p21(+/+)) mice in 85-90% O(2) for 4 d. We found that newborn p21(-/-) mice exposed to O(2) had decreased survival in hyperoxia compared with p21(+/+) mice (P < 0.01). At 2 and 6 wk after exposure to neonatal hyperoxia, p21(-/-) O(2) lung had significantly larger alveoli then p21(-/-) control lung, as assessed by mean alveolar size and mean linear intercept. Pulmonary function tests at 6 wk demonstrated increased lung volume in both p21(-/-) and p21(+/+) O(2) mice consistent with altered lung growth from neonatal exposure to hyperoxia. Antibodies to nitrotyrosine, a marker for oxidative stress revealed that at 2 and 6 wk of age, p21(-/-) O(2) lung had significantly more oxidative stress than p21(-/-) and p21(+/+) control and p21(+/+) O(2) lung. We therefore conclude that p21 confers some additional protection to the lung during exposure to neonatal hyperoxia. Furthermore, p21 may be important during recovery from lung injury because it is associated with lower levels of oxidative stress and increased oxidative stress may contribute to alveolar growth abnormalities in the p21(-/-) O(2) lung.
Full-text · Article · May 2004 · American Journal of Respiratory Cell and Molecular Biology
[Show abstract][Hide abstract] ABSTRACT: 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.
Preview · Article · May 2004 · Journal of Applied Physiology
[Show abstract][Hide abstract] ABSTRACT: 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.
Preview · Article · Oct 2003 · Journal of Applied Physiology
[Show abstract][Hide abstract] ABSTRACT: Insulin-dependent diabetes mellitus (IDDM) can lead to ventilatory depression and decreased sensitivity to hypercapnia. We examined relationships between ventilation, plasma insulin, leptin, ketones, and blood glucose levels in two mouse models of IDDM: (1) streptozotocin-induced diabetes in C57BL/6J mice on a regular diet or with induced obesity from a high fat diet; and (2) spontaneous diabetes mellitus in NOD-Ltj mice. In both mouse models, IDDM resulted in depression of the hypercapnic ventilatory response (HCVR). This ventilatory depression was not associated with decreases in plasma insulin or leptin levels. There was, however, a strong association between the duration of hyperglycemia, the decline in HCVR, and increased glycosylation of the diaphragm. Hyperventilation was observed in only six of 14 C57BL/6J obese wild-type mice, despite a significant degree of diabetic ketoacidosis (DKA) in all 14 animals. In mice with DKA, there was a significant correlation between the increase in baseline minute ventilation (V E) and hyperleptinemia (r = 0.77, p < 0.01). In leptin-deficient C57BL/6J-Lep(ob) mice, low levels of both V E and ketones were observed. These results suggest that: (1) depression of the HCVR in IDDM is associated with hyperglycemia and glycosylation of the diaphragm; and (2) the hyperventilation of DKA is leptin dependent.
Full-text · Article · Mar 2001 · American Journal of Respiratory and Critical Care Medicine
[Show abstract][Hide abstract] ABSTRACT: Appointing physiological function to specific genetic determinants requires a systems physiologist to consider ways of assessing precise phenotypic mechanisms. The integration of ventilation, metabolism and thermoregulation, for example, is very complex and may differ among small and large mammalian species. This challenge is particularly applicable to the study of short- and long-term adaptation of these systems to hypoxic exposure associated with high altitude. Our laboratory has initiated a research effort to dissect the complexity of hypoxic adaptation using traditional quantitative genetic analysis and contemporary DNA genotyping techniques. Although the current evidence in murine models demonstrates that specific genes influence control of hypoxic ventilatory responses (HVR), the relevance of these determinants to human adaptation to altitude remains open to exploration. Our review discusses the progress and uncertainties associated with assigning a genetic basis to variation in acute and chronic HVR.
No preview · Article · Feb 2001 · High Altitude Medicine & Biology