Test and evaluation of exercise-enhanced preoxygenation in U-2 operations.

BACKGROUND: Preoxygenation to prevent decompression sickness (DCS) during U-2 reconnaissance flights requires considerable time and occasionally does not provide adequate protection. Increasing preoxygenation within a practical period of time provides marginally increased protection and is not always operationally feasible. Including exercise during preoxygenation to increase muscle tissue perfusion, cardiac output, and ventilation can improve the quality of the denitrogenation. METHODS: A pilot, who reported two cases of DCS during his first 25 U-2 high flights involving cabin altitudes of 29,000-30,000 ft, volunteered to test exercise-enhanced preoxygenation. He performed 10 min of strenuous upper and lower body exercise at the beginning of preoxygenation prior to subsequent high flights without increasing total preoxygenation time. RESULTS: The exercise was performed at 75% of maximal oxygen uptake based on the estimated maximal oxygen uptake determined during an Air Force aerobic fitness test and heart rate. The pilot's next 36 high flights, using exercise-enhanced preoxygenation, were completed with no reports of DCS. CONCLUSIONS: This statistically significant operational test reinforced the laboratory studies. Implementation of this procedure for reducing DCS in susceptible U-2 pilots and collecting additional data from the U-2 pilot population is recommended.

Lung function during moderate hypobaric hypoxia in normal subjects and patients with chronic obstructive pulmonary disease.

BACKGROUND: We sought to describe changes in spirometric variables and lung volume subdivisions in healthy subjects and patients with chronic obstructive pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during air travel. We further questioned whether changes in lung function may associate with reduced maximum ventilation or worsened arterial blood gases. METHODS: Ambulatory patients with COPD and healthy adults comprised the study populations (n = 27). We obtained baseline measurements of spirometry, lung volumes and arterial blood gases from each subject at sea level and repeated measurements during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had declines in FVC during altitude exposure greater than the 95% confidence interval (CI) for expected within day variability (p < 0.05). Average forced vital capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, -0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did not differ between groups (p > 0.05) and correlated with increasing residual volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p = 0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p < 0.05). Changes in spirometric variables for patients and controls did not explain significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some COPD patients and normal subjects greater than expected for within day variability. Spirometric changes correlated with changes in reduced maximum voluntary ventilation in the patients but not with changes in resting arterial blood gases.

Effects of hyperoxia and caffeine on the expression of fragile site at Xq27.3.

To enhance the cytogenetic expression of the fragile X chromosome, we studied the effects of hyperoxia and caffeine on the induction of fragile Xq27.3. A lymphoblastoid cell line (GM 06912) derived from a fragile X male proband was cultured in RPMI 1640 containing 16% dialyzed fetal calf serum. The cells were synchronously subjected to one of 3 different atmospheric oxygen tensions (21%, 21.3 kPa, normoxic; 40%, 40.5 kPa, hyperoxic; or 60%, 60.8 kPa, hyperoxic) during the last 24 hours of the 72 hour culture, immediately after the addition of 2'-deoxy-5-fluorouridine (FUdR) at 25 ng/ml. To study the enhancing effect of caffeine, with or without hyperoxia, a second set of cultures was additionally subjected to caffeine (2.5 mM) during the last 6 hours of the culture. When the fragility of hyperoxic cells (38.1 kPa dissolved oxygen) was compared to that of normoxic control cells (13.3 kPa dissolved oxygen), the difference was significant (P < 0.05). These data suggest that there is a mean increase in the fragile Xq27.3 expressivity as the dissolved oxygen tension increases. Additionally, we observed that caffeine, with or without hyperoxia, significantly (P < 0.05) suppressed the expression of the fragile X site in this lymphoblastoid cell line.

Effect of upright and supine posture on hypoxemia during air transport.

BACKGROUND: Change in body position can cause hypoxemia at sea level in patients with lung diseases. Because of concern for the added risk of hypoxemia during air transport, we investigated the effect of body position on arterial oxygen partial pressure (PaO2) in individuals with lung disease under conditions of hypobaric hypoxia. METHOD: The study groups consisted of 8 patients with chronic obstructive lung disease, 4 patients with interstitial lung disease, and 6 healthy subjects. We obtained samples from radial artery catheters at sea level (SL) and altitude (ALT) simulation of 8000 ft (2438 m) in a hypobaric chamber in supine and upright postures. RESULTS: Altitude exposure did not result in a significant change in mean supine minus mean upright PaO2 (dPaO2); however, some individuals had large changes at SL. Moreover, the variance for dPaO2 was significantly smaller at ALT compared to SL with all groups combined (F test, p < 0.05). We found no correlation between dPaO2 at SL vs. ALT (p = 0.293; r = 0.262; n = 18). At both SL and ALT, dPaCO2 correlated negatively with dpH. At SL, dPaO2 did not correlate with either dPaCO2 or dpH; at ALT dPaO2 correlated with dpH (p < 0.05) and correlated negatively with dPaCO2 (p < 0.01). CONCLUSION: We conclude that significantly less postural variation in PaO2 occurs at moderate ALT compared to SL. In our patients with diffuse bilateral pulmonary disease, postural change did not contribute significantly to hypoxemia experienced at ALT. We infer that greater ventilatory response to hypoxemia at ALT in either posture may explain this finding.

Visual performance with the Aviator Night Vision Imaging System (ANVIS) at a simulated altitude of 4300 meters.

This study determined if visual performance with Aviator Night Vision Imaging System (ANVIS) was degraded by the degree of hypoxia experienced at the maximum flight altitude currently authorized (U.S. Army regulations) without supplemental oxygen. Visual acuity and contrast sensitivity with ANVIS were tested under simulated starlight and full moonlight illumination in a hypobaric chamber: at ground level (93 m), 5 min and 30 min after ascent to 4300 m, and 10 min after return to ground level. Visual acuity was significantly (p < 0.05) degraded by a small amount (0.05 log minimal angle resolvable) after 30 min at 4300 m. Contrast sensitivity was not significantly degraded at any time. No significant difference between males (n = 11) and females (n = 6) on any measure of visual performance was detected. Females did have a significantly lower percent oxygen saturation of hemoglobin compared with males at altitude (72% versus 80% after 30 min). The results suggests that visual acuity ANVIS is degraded slightly after 30 min of exposure to 4300 m, although less than what would be expected with unaided night vision under these conditions.

Space shuttle flight (STS-45) of L8 myoblast cells results in the isolation of a nonfusing cell line variant.

Myoblast cell cultures have been widely employed in conventional (1g) studies of biological processes because characteristics of intact muscle can be readily observed in these cultured cells. We decided to investigate the effects of spaceflight on muscle by utilizing a well characterized myoblast cell line (L8 rat myoblasts) as cultured in the recently designed Space Tissue Loss Flight Module "A" (STL-A). The STL-A is a "state of the art," compact, fully contained, automated cell culture apparatus which replaces a single mid-deck locker on the Space Shuttle. The L8 cells were successfully flown in the STL-A on the Space Shuttle STS-45 mission. Upon return to earth, reculturing of these spaceflown L8 cells (L8SF) resulted in their unexpected failure to fuse and differentiate into myotubes. This inability of the L8SF cells to fuse was found to be a permanent phenotypic alteration. Scanning electron microscopic examination of L8SF cells growing at 1g on fibronectin-coated polypropylene fibers exhibited a strikingly different morphology as compared to control cells. In addition to their failure to fuse into myotubes, L8SF cells also piled up on top of each other. When assayed in fusion-promoting soft agar, L8SF cells gave rise to substantially more and larger colonies than did either preflight (L8AT) or ground control (L8GC) cells. All data to this point indicate that flying L8 rat myoblasts on the Space Shuttle for a duration of 7-10 d at subconfluent densities results in several permanent phenotypic alterations in these cells.

Evaluation of antimicrobials combined with hyperbaric oxygen in a mouse model of clostridial myonecrosis.

The efficacy of hyperbaric oxygen (HBO) alone and in combination with several antimicrobial agents was evaluated in a lethal model of gas gangrene in mice. Intraperitoneal administration of penicillin, imipenem, clindamycin, or metronidazole immediately followed inoculation of > 10(9) CFU of Clostridium perfringens type A in mice. Mice treated with hyperbaric oxygen were exposed twice a day to 100% oxygen at 303 kilopascals (kPa) pressure for 90 minutes. The total exposure time to HBO for surviving animals was 9 hours. Control (saline-injected) mice treated with HBO alone did not have an enhanced survival rate when compared with mice exposed to air at ambient pressure. Survival of infected mice treated with either clindamycin or metronidazole was significantly longer than that of groups treated with penicillin or imipenem (p < 0.05). Hyperbaric oxygen alone or in combination with the four antimicrobial agents evaluated did not statistically improve survival of mice infected with a lethal dose of C. perfringens.

Hyperbaric hyperoxia enhances the lethal effects of amphotericin B in Leishmania braziliensis panamensis.

Leishmania braziliensis panamensis promastigotes were exposed in vitro to amphotericin B (AmB), menadione, or phenazine methosulfate under normoxic conditions. Promastigotes were also exposed to hyperoxia alone (100% O2 at total pressures of 101.3 or 253.3 kPa), or combined with drugs. After incubation for 24 h at 27 degrees C, viable promastigotes were stained with fluorescein diacetate and counted using epifluorescence microscopy. Hyperbaric hyperoxia alone (PO2 = 229.3 kPa) was as effective as AmB alone (0.2 microM); both reduced the number of viable promastigotes to approximately 13% of the original inoculum. In addition, AmB in a hyperbaric hyperoxic environment killed more promastigotes (97% of the original inoculum) than AmB in normoxic (PO2 = 21.1 kPa) or hyperoxic conditions (PO2 = 91.7 kPa). Finally, AmB in hyperbaric hyperoxia killed significantly more (75%) promastigotes than hyperbaric hyperoxia alone. High oxygen tensions did not significantly alter the lethal effects of either menadione or phenazine methosulfate. In conclusion, the lethal effects of low dose AmB in Leishmania promastigotes were augmented by hyperbaric hyperoxia in vitro, but only at oxygen doses too high to be tolerated by human patients.

Oxygen supplementation during air travel in patients with chronic obstructive lung disease.

The objective of this study was to quantitate the effects of O2 supplementation by nasal cannula (NC) and Venturi mask (VM) on PaO2 in patients with chronic obstructive pulmonary disease (COPD) during acute hypobaric exposure, simulating a commercial jet aircraft cabin. We conducted a crossover intervention trial in which subjects served as their own controls in an ambulatory outpatient pulmonary disease service of a tertiary care military medical center and a hypobaric research facility. The subjects were a volunteer sample of 18 men with stable severe COPD, not requiring long-term O2 therapy, and uncomplicated by hypercapnea or cardiac disease. Mean age was 68 years, and mean FEV1 was 0.97 L (31.3 percent predicted). We exposed patients to conditions equivalent to 8,000 feet in a hypobaric chamber. Radial artery catheters provided blood samples at ground level and 8,000 feet. O2 was sequentially administered at 8,000 feet by NC at 4 L/min and 24 percent or 28 percent VM. We describe changes in blood gas data from baseline values and between interventions. O2 at 4 L/min NC flow at 8,000 feet caused PaO2 to increase from 47.4 +/- 6.3 mm Hg to 82.3 +/- 14 mm Hg (n = 18), an increase of 34.9 +/- 14.8 mm Hg. Supplementation of O2 by 24 percent VM caused PaO2 at 8,000 feet to increase by 12.7 +/- 3.8 mm Hg. Twenty-eight percent VM caused PaO2 at 8,000 feet to increase by 19.7 +/- 8.2 mm Hg. Changes in PaO2 with 4 L/min NC were greater than those with either VM. The increase with 28 percent VM was greater than that caused by 24 percent VM (p less than 0.05). Compared with ground level, 4 L/min NC increased mean PaO2 by 9.9 +/- 12.6 mm Hg; 24 percent and 28 percent VM did not cause mean PaO2 to increase above ground level values. We describe a range of capability of familiar O2 therapy devices to increase PaO2 to levels that will maintain tissue oxygenation of patients during acute altitude exposure.

Accuracy of oxyhemoglobin saturation monitors during simulated altitude exposure of men with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are at risk for hypoxemia during air travel. We assessed the comparative performance of oxyhemoglobin saturation (%O2Hb) monitors on these patients during hypobaric exposure. We measured %O2Hb by arterial catheter blood co-oximetry (COOX) and compared these values to those from a transmittance ear oximeter and a reusable digital pulse oximeter. Additionally, we examined the effect of oxygen supplementation (4 L/min) on %O2Hb. A total of 18 ambulatory males with severe COPD were exposed to 8,000 ft (565 mm Hg) in a hypobaric chamber. Multiple measures of %O2Hb were made with each monitor at sea level and at 8,000 ft, with and without supplemental oxygen. By COOX, %O2Hb fell at altitude to clinically significant levels, and was subsequently corrected with supplemental oxygen. Saturations measured by the transmittance ear oximeter were very close to the COOX, underestimating the true value by only 0.6% at altitude (p less than 0.05), while the reusable digital pulse oximeter over-estimated %O2Hb alinearly by a mean of 3.8% at altitude.

Modification of an automated vascular diagnostic system for hyperbaric use.

Modifications of an automated, noninvasive vascular diagnostic system (VASCULAB, MedaSonics, Inc.) for measuring blood pressure and plethysmographic blood flow responses to normobaric and hyperbaric oxygenation are described. The system consisted of a pump for inflating and deflating blood pressure cuffs and a microprocessor program controller (VSC21) with ultrasound Doppler, strain-gauge plethysmograph, and chart recorder. Inclusion of the VSC21 controller in the chamber was required for performance of procedures that could not be controlled from outside the chamber. All other components were outside the chamber. For fire prevention the VSC21 controller was nitrogen-purged in an acrylic case mounted on a mobile cart. Pressure-cuff tubes were attached via adapted fittings and connectors in the cart to connector ports in the controller's front panel. Electrical power cables and instrument signal wires were routed through chamber penetrations to an electrical power source and other VASCULAB components, respectively, outside the chamber. Initially, compression of the chamber to pressures in excess of 1.68 bar disabled the VSC21, requiring removal of its front membrane panel and ventilation of its pressure-sensitive keypad switches. This allowed automated assessment of blood pressure and calf blood flow at test pressures of 1.97 and 2.96 bar.

Hypoxemia during air travel in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To quantitate and identify determinants of the severity of hypoxemia during air travel in patients with chronic obstructive pulmonary disease. DESIGN: Prospective study of physiologic variables before and during intervention. SETTING: Referral-based pulmonary disease clinic at a U.S. Army medical center. PATIENTS: Eighteen ambulatory retired servicemen (age 68 +/- 6 [SD] years) with severe chronic obstructive pulmonary disease (forced expiratory volume in the first second [FEV1] 31% +/- 10% of predicted). INTERVENTION: Altitude simulation equivalent to 2438 meters (8000 feet) above sea level in a hypobaric chamber. MEASUREMENTS AND MAIN RESULTS: Radial artery catheter blood oxygen tension in the patients declined from a ground value (PaO2G) at sea level of 72.4 +/- 9 mm Hg to an altitude value (PaO2Alt) of 47.4 +/- 6 mm Hg after 45 minutes of steady state hypobaric exposure. The PaO2G correlated with PaO2Alt (r = 0.587; P less than 0.01). Multiple regression analysis revealed that the preflight FEV1 reduced the variability in PaO2Alt not explained by PaO2G in the equation: PaO2Alt = 0.453 [PaO2G] + 0.386 [FEV1% predicted] + 2.440 (r = 0.847; P less than 0.001). Residuals from two previously published formulas using PaO2G also correlated with FEV1 (r greater than or equal to 0.765; P less than 0.001). CONCLUSIONS: Arterial blood oxygen tension declined to clinically significant levels in most patients during hypobaric exposure. When combined with the preflight arterial PO2 at ground level (PaO2G), the measurement of the preflight FEV1 improved prediction of PaO2 at altitude (PaO2Alt) in patients with severe chronic obstructive pulmonary disease.

Potential applications for digital image processing at the Armed Forces Institute of Pathology.

Digital image processing systems are fast becoming valuable tools in the quantitative study of visual images. These systems not only enhance image features, but provide the investigator with information about those features expressed in numeric form. Now, statistical analyses can be performed on information that was formerly only qualitative. At the Armed Forces Institute of Pathology (AFIP), we are studying the potential applications of digital image processing systems to a variety of problems including morphological analysis of cell, tissue, and organ samples; reconstruction and enhancement of photographic images; three-dimensional reconstruction of organ systems; analysis of terrain, material, and human remains involved in aircraft accidents; and the archiving of histological images and pathological records. This report outlines the basic characteristics of image processing systems and discusses their potential applications in pathological studies at the AFIP. Information was collected from interviews with the AFIP professional staff.

A photometric analysis of free alveolar macrophages (FAMs) in smoking and nonsmoking firefighters.

The effects of cigarette smoking and chronic smoke inhalation were evaluated in free alveolar macrophages (FAMs) in firefighters and police officers from the city of Denver, CO. Evaluation was accomplished by comparing statistical morphometric and photometric data taken from digital images of FAMs generated by the microscope photometer. Although our results failed to show significant differences between occupations and smoking status in FAM size, degree of size variability, or nuclear/cytoplasmic area ratios, they did demonstrate a significant difference in the degree of nuclear and cytoplasmic optical density (O.D.) between both occupation and smoking status. Firefighters consistently showed significantly greater O.D. values than police officers while smokers demonstrated a significantly greater O.D. than nonsmokers. While the meaning of these findings remains illusive, they do, however, present quantitative data supporting the biological response of the FAM to occupational and cigarette smoke inhalation.

Topical effects of molten salt on rat integument: a histological and photometric assessment.

The topical effects of the molten salt 1-methyl-3-ethylimidazolium tetrachloroaluminate (melt) and its organic component, the organic salt 1-methyl-3-ethylimidazolium chloride were tested on rat integument. Evaluation was accomplished using standard histological techniques supplemented with digital analysis using the microscope photometer. Two groups of animals were treated with 1.5 ml of either the melt or the organic salt for 10 consecutive days. A third group treated with the melt had the treated area flushed with running water 5 min after each application (wash). Significant treatment effects were observed in rats treated with the melt and wash preparations while the effects of the organic salt were unremarkable. The melt induced an ulcerative dermatitis with acanthosis while the wash produced only mild acanthosis and dermatitis. This damage appears to result from the penetration of aluminum chloride in the melt through the skin and its toxic effects on the cells of the dermis and epidermis.