Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 102: 1099-1104, 2007. First published November 9, 2006; doi:10.1152/japplphysiol.01539.2005
8750-7587/07 $8.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
102/3/1099    most recent
01539.2005v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dainer, H.
Right arrow Articles by Mahon, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dainer, H.
Right arrow Articles by Mahon, R.

Short oxygen prebreathing and intravenous perfluorocarbon emulsion reduces morbidity and mortality in a swine saturation model of decompression sickness

Hugh Dainer, John Nelson, Kathryn Brass, Elizabeth Montcalm-Smith, and Richard Mahon

Undersea Medicine Department, Naval Medical Research Center, Silver Spring, Maryland

Submitted 8 December 2005 ; accepted in final form 7 November 2006


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Disabled submarine (DISSUB) survivors will achieve inert gas tissue saturation within 24 h. Direct ascent to the surface when saturated carries a high risk of decompression sickness (DCS) and death, yet may be necessary during rescue or escape. O2 has demonstrated benefits in decreasing morbidity and mortality resulting from DCS by enhancing inert gas elimination. Perfluorocarbons (PFCs) also mitigate the effects of DCS by decreasing bubble formation and increasing O2 delivery. Our hypothesis is that combining O2 prebreathing (OPB) and PFC administration will reduce the incidence of DCS and death following saturation in an established 20-kg swine model. Yorkshire swine (20 ± 6.5 kg) were compressed to 5 atmospheres (ATA) in a dry chamber for 22 h before randomization into one of four groups: 1) air and saline, 2) OPB and saline, 3) OPB with PFC given at depth, 4) OPB with PFC given after surfacing. OPB animals received >90% O2 for 9 min at depth. All animals were returned to the surface (1 ATA) without decompression stops. The incidence of severe DCS < 2 h after surfacing was 96%, 63%, 82%, and 29% for groups 1, 2, 3, and 4, respectively. The incidence of death was 88%, 41%, 54%, and 5% for groups 1, 2, 3, and 4, respectively. OPB combined with PFC administration after surfacing provided the greatest reduction in DCS morbidity and mortality in a saturation swine model. O2-related seizure activity before reaching surface did not negatively affect outcome, but further safety studies are warranted.

disabled submarine; nitrogen

A DIVER'S BODY absorbs inert gases as a function of the depth and duration of dive, breathing mixture composition, individual diver characteristics, and environmental conditions (9, 19, 27). After remaining at depth for extended periods, a diver's body becomes saturated, with equal amounts of inert gas entering and leaving the body. Divers will achieve inert gas tissue saturation within 24 h at any given depth (5). Saturation diving operations permit divers to live and work at depth with a singular decompression obligation at the conclusion of the dive (25). However, decompression from saturation conditions is lengthy, an obligation in excess of 16 h when saturated at only 50 feet of seawater (fsw) (14). Direct ascent to the surface [1 atmosphere (ATA) of pressure] from saturation conditions carries a high risk of decompression sickness (DCS) and death (37) and yet may be necessary in certain situations such as commercial diving accidents, equipment malfunction, and disabled submarine (DISSUB) escape or rescue.

While there is no definitive etiology of DCS, bubbles are believed to form from inert gas exiting supersaturated tissues during rapid decompression (17). Bubbles may be directly responsible for DCS symptoms or may initiate a biochemical cascade with serious indirect effects, including leukocyte adhesion, platelet aggregation, and complement activation (13, 24, 28). In controlled environments, optimal decompression follows established schedules, allowing the time needed to slowly eliminate dissolved gas and minimize bubble formation (2, 35, 37). This is normally achieved by one of the following methods: 1) controlled ascent within the water column; or 2) after surfacing, rapid recompression in a hyperbaric chamber to the depth of saturation followed by slow measured decompression. However, operational scenarios, remote locations, or emergency situations may prohibit these options, and alternative means to prevent, attenuate, or treat DCS are required.

The known ability of oxygen (O2) to reduce DCS morbidity and mortality has been attributed to enhanced elimination of dissolved inert gas and improved tissue oxygenation (3). Hyperbaric O2 (HBO) has been shown to decrease leukocyte adhesion, decrease platelet aggregation, and affect complement activation (8, 33). Therefore, the use of O2 at depth holds the promise for benefits beyond inert gas elimination that may further improve outcomes in situations of rapid ascent from saturation to 1 ATA.

Another means to mitigate the effects of DCS may be the use of perfluorocarbons (PFCs). PFCs are synthetic straight-chain and aromatic hydrophobic hydrocarbons first developed for industrial use but later adapted for biological use through combination with organic emulsification agents (10, 11, 20). PFCs dissolve more N2 and O2 than plasma and therefore may decrease inert gas bubble formation and enhance tissue O2 delivery (4, 36). In this experiment, we report the findings of a short O2 prebreathing (OPB), both with and without intravenous PFC emulsion, in a 20-kg swine model saturated at 132 fsw for 22 h before direct ascent to surface pressure.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The experiments reported were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, National Academy Press (1996). Before commencing, our Institutional Animal Care and Use Committee reviewed and approved all aspects of this protocol. The institutional animal care facility is fully AALAC accredited, and staff members are familiar with our swine saturation model (7).

Subjects.   All animals were neutered male Yorkshire swine (20 ± 6.5 kg). On receipt, each was examined by a veterinarian, fitted with an adjustable chest harness, and housed in individual runs with freely available water. Daily feedings consisted of 2% by body weight of laboratory animal feed (Harlan Teklad, Madison, WI). The animals remained in the care facility for a minimum of 72 h, adjusting to their new surroundings before any experiments.

Predive preparation.   Animals were moved in plastic transport kennels to the surgical suite of the animal housing facility, placed in a Panepinto sling, and anesthetized by intramuscular injection of 20 mg/kg ketamine and 1 mg/kg xylazine. Under sterile conditions, eight-gauge catheters were placed into the left exterior jugular vein and tied in place. All animals received a dose of chloramphenicol (25 mg/kg) intravenously to prevent infection. Following anesthetic recovery, animals were returned to the housing facility and received no further interventions that day.

Dive protocol.   Three animals were compressed during each saturation test dive. The morning after intravenous catheterization, animals were transported to the chamber building, weighed, and placed into clear Plexiglas observation crates modified to allow gas switching at depth. Intravenous lines were connected through hull penetrators to pumps outside the chamber, allowing the administration of medications at depth. Drinking water was available ad libitum while at depth.

The chamber was progressively compressed to 132 fsw (5 ATA) equivalent with air. Compression began at a rate of 0.15 ATA/min. If no animal showed distress or other evidence of middle ear barotraumas at 2 ATA, the descent rate was increased to 0.30 ATA/min to 4 ATA, and then further increased to a rate of 0.45 ATA/min until reaching test pressure. During the dive, animals were monitored and recorded via closed-circuit television cameras through observation ports. Atmospheric samples in all boxes and in the chamber were continuously monitored and recorded. Temperature was maintained between 26.7 and 29.4°C, humidity between 50 and 75%, and CO2 concentration <0.3% (Abbeon certified hygrometer and temperature indicator, model HTAB169B, Abbeon Cal, Santa Barbara, CA).

The experiments in this study used Oxygent, an intravenous PFC emulsion (60% weight per volume perflubron-based emulsion, Alliance Pharmaceutical, San Diego, CA). Oxygent is a second-generation emulsion with good safety and tolerability (18, 26). After 22 h at depth, animals were randomized to receive one of four breathing mixtures and intravenous infusion treatments: 1) air and normal saline (Air); 2) O2 and saline (OPB); 3) O2 and 6 ml/kg PFC administered at depth (B-PFC); and 4) O2 at depth with 6 ml/kg PFC given on surface after decompression (S-PFC). All saline infusions were equal in volume to PFC infusions, and each group was held to the same timeline of events (Fig. 1). The pressure required to pump fluid through the intravenous tubing at depth limited the speed of PFC emulsion boluses to 20 min. PFC emulsion administered on the surface required 10 min to complete. Animals were switched from air to O2 following PFC infusion; O2 was >90% in <3 min of gas switch, and the animal remained on O2 for the remainder of the hyperbaric exposure and decompression. Animals were monitored continuously for signs of seizure activity. After 9 min on >90% O2 (except for the air group), animals remained on the specified randomized breathing mixture during decompression to 1 ATA at a steady rate of 30 fsw/min (0.91 ATA/min).


Figure 1
View larger version (9K):
[in this window]
[in a new window]

  		Fig. 1. Timeline for administration of perfluorocarbon (PFC) and O2 for all groups. RB, reached bottom; LB, left bottom; RS, reached surface. Air, control group; OPB, O2 prebreathing; S-PFC, O2 prebreathing and PFC on surface; B-PFC, O2 prebreathing and PFC given at depth.

 
Observations at depth and through decompression.   Approximately 30 min before the intravenous infusion at depth, a dedicated observer began independently monitoring each animal. Respiratory distress, agitation, seizure activity, and any abnormal behavior were recorded. Sustained seizure activity was treated with intravenous Diazepam (2.5 mg). Observations continued for all animals with recorded seizures, and these animals were included in the data analysis.

Surface observations.   On return to surface pressure, the breathing mixture was switched from O2 back to air. Observers entered the chamber to continue observations and recording for an additional 2 h. Animals remained inside separate Plexiglas containers throughout the surface observation period. Neurological DCS was defined as motor weakness (limb weakness, repeated inability to stand after being righted by the investigator), paralysis (complete limb dysfunction, areflexia, hypotonia), sensory compromise (lack of retraction from painful stimuli), or cranial nerve dysfunction. Cardiopulmonary DCS was defined as a visually observed respiratory rate of 60 breaths/min combined with respiratory distress, as evidenced by open-mouthed, labored breathing, central cyanosis, or the production of frothy white sputum. The onset of severe DCS (neurological or cardiopulmonary dysfunction) and all behavioral signs and symptoms were recorded to the nearest minute. Subjects with signs of severe DCS were given intravenous diazepam (2.5 mg) through the indwelling catheter as necessary to alleviate their distress. Skin DCS and behavioral features indicative of mild DCS (e.g., limb lifting) were recorded but not classified as positive cases for this study.

After the 2-h observation period, survivors were thoroughly examined by the principal investigator and euthanized with 5 ml bolus of Euthasol. The natural history of morbidity and mortality has been shown to plateau by 1 h in the Naval Medical Research Center 20-kg swine saturation model (7). The 2-h observation period was chosen to provide additional time for possible increased latency due to partially effective treatment while continuing to limit observations to what would be used for triage of survivors during a DISSUB scenario.

Statistics.   Mean weights before the hyperbaric exposure were compared with ANOVA and post hoc with Dunnett's test against air controls. Development of DCS and death were displayed in the Kaplan-Meier method and then compared with the log rank test. Next, paired groups were compared using a Cox proportional-hazards regression; 95% confidence intervals (CIs) were recorded and a P < 0.05 was considered significant. The Peto test was used to explore differences in DCS latency, both among all groups and between specific groups. The relationship of seizure activity and mortality outcome were compared using the Fisher's exact test. Minitab or Statistix (version 8.0) software packages were used for all calculations.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Baseline weight.   Mean weights (Table 1) before dive exposure (16.2–26.6 kg) were not different among groups by ANOVA (P = 0.396).


View this table:
[in this window]
[in a new window]

  		Table 1. Baseline weights, overall occurrence of DCS and death, and relative risk for Air group vs. other groups

 
DCS.   In the Air group (Table 1), 25/26 animals (96%) suffered DCS <2 h after returning to surface pressure. In the B-PFC group, which received PFC at depth in addition to OPB, 18/22 (82%) suffered DCS <2 h after returning to surface pressure. In the O2 (OPB-only) group and S-PFC groups, 17/27 (63%) and 6/21 (29%) experienced DCS within the 2-h observation period, respectively. Log-rank testing of the Kaplan-Meier method (Fig. 2) showed a significant treatment effect among the combined groups with a P < 0.0001. Paired groups were then analyzed by Cox proportional-hazards regression. The relative risk for DCS in the Air vs. OPB groups was 3.22 (95% CI 1.70, 6.1; P < 0.0001). The relative risk for DCS in the Air vs. S-PFC groups was 12.1 (95% CI 4.58, 32.0; P < 0.0001). We also determined that the relative risk for OPB vs. S-PFC (Table 2) was 3.23 (95% CI 1.27, 8.20; P < 0.05). The relative risk for Air vs. B-PFC did not reach statistical significance and was 1.59 (95% CI 0.87, 2.92; P = 0.132).


Figure 2
View larger version (15K):
[in this window]
[in a new window]

  		Fig. 2. Kaplan-Meier plots for decompression sickness (DCS) occurrence.

 

View this table:
[in this window]
[in a new window]

  		Table 2. Baseline weights, overall occurrence of DCS and death, and relative risk of OPB vs. S-PFC group

 
DCS latency.   Initial review of the Kaplan-Meier plots (Fig. 2) appeared to show an increase in the average time of onset of DCS in the non-Air group animals. This was explored with the Peto test, which showed that among all groups there was a significant difference in the latency of symptoms (P < 0.0001). Further evaluations were then performed with the Peto test to compare differences in latency (results rounded to the nearest minute) between individual groups (Table 3). Censoring of animals that did not experience DCS prevented skewing of the mean times of latency for groups toward the maximum value of 120 min for animals that did not exhibit DCS symptoms. The B-PFC group did not differ significantly in latency compared with the air group (P = 0.075). However, both O2 and S-PFC groups demonstrated a significant increase in time to onset of DCS compared with the Air group (P < 0.001 and P <0.0001, respectively). Additionally, the S-PFC group was found to have significantly increased latency compared with the B-PFC group (P < 0.0001).


View this table:
[in this window]
[in a new window]

  		Table 3. Latency in onset of DCS in minutes

 
Death.   Death (Table 1) was observed during the 2-h surface observation in 23/26 (88%) of the Air group, 12/22 (54%) of the B-PFC group, 11/27 (41%) of the OPB group, and 1/21 (5%) of the S-PFC group. Log-rank testing of the Kaplan-Meier method (Fig. 3) showed a significant difference among the four groups (P < 0.0001). Cox proportional-hazards regression between paired groups showed that the relative risk of death for animals receiving Air vs. B-PFC was 2.10 (95% CI 1.04, 4.24; P < 0.05); OPB was 3.28 (95% CI 1.59, 6.79; P < 0.001); and Air vs. S-PFC was 39.2 (95% CI 5.21, 294.0; P < 0.001). We also compared OPB vs. S-PFC (Table 2) and determined that the relative risk was 10.02 (95% CI 1.32, 77.69; P < 0.05).


Figure 3
View larger version (14K):
[in this window]
[in a new window]

  		Fig. 3. Kaplan-Meier plots for death occurrence.

 
Seizure activity.   Seizure activity was observed in 5/26 (19%) of the Air group, 9/22 (41%) of the B-PFC group, 12/27 (44%) of the OPB group, and 2/21 (9.5%) of the S-PFC group. When reviewed with attention to the time of onset, seizure activity appeared to be separated into two groups: 1) seizures occurring below the surface (BS) with lower mortality, and 2) seizures occurring after reaching the surface (AS) with higher mortality. The Fisher exact tests (Table 4) showed a significant difference between BS and AS seizures (P < 0.01). The odds ratio of death following AS vs. BS seizure was 15.13 (95% CI 2.28, 100.3).


View this table:
[in this window]
[in a new window]

  		Table 4. Fisher exact tests of seizure groups and of >90% O2 groups

 
Seizure activity below the surface occurred in all three groups of animals with exposure to >90% O2 at depth (B-PFC, OPB, and S-PFC). Animals in these groups were subdivided into two groups on the basis of observation of seizure activity at depth: 1) BS seizure and 2) no seizure activity or AS only (NBS). With preliminary review, the presence or absence of BS seizure activity did not appear to alter mortality rate. This was assessed further with the Fisher exact tests (Table 4), which demonstrated no significant difference between the BS and NBS seizure groups (P = 0.19). The odds ratio of death following BS seizure vs. NBS seizure was also not significant with a value of 0.28 (95% CI 0.06, 1.43).


   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
In this study we demonstrate that OPB with or without an intravenous PFC emulsion substantially decreases the rates of both DCS and death within a 2-h observation period after rapid decompression from saturation. Reduction in DCS was most marked when 10 min OPB at depth was combined with PFC administration after animals had returned to surface pressure.

OPB has previously been demonstrated to decrease DCS from hypobaric exposure and is a standard procedure in high-altitude operations to include high-altitude aircraft and extravehicular space missions (38). The mechanisms underlying the beneficial effects of short-term OPB may be related to both the direct physical effects of a partial washout of inert gases (31) and indirectly to the known pharmacological properties of HBO. HBO may decrease DCS by inhibition of neutrophil adherence (33), decreased platelet aggregation (8), and enhancing nitric oxide formation (32). These effects have the potential to maintain benefit beyond the period of HBO exposure.

The effectiveness of PFC both with and without hyperoxic exposure has been previously demonstrated in animal models (6, 23, 29). However, we were impressed by the marked reduction in DCS when OPB at depth and PFC administration at surface pressures was combined. Our results also demonstrate that the combination reduces rates of DCS and death below those achieved in a similar swine saturation study that used surface administration of PFC without an OPB (6). Known properties of PFCs make them a logical adjunctive therapy for DCS.

PFCs are synthetic straight-chain and aromatic hydrophobic hydrocarbons first developed for industrial use but later adapted for biological use through combination with organic emulsification agents (10, 11, 20). The solubility of O2 in PFC is 20–25 times greater than that of water or blood plasma and approaches 60 vol% (whole blood carries 20 vol%). The N2-carrying capacity of PFC emulsions approaches 50 vol% (by comparison, plasma N2 solubility is 0.015 vol%) (6, 29). While biological molecules, such as hemoglobin, form chemical bonds with gases, PFCs do not bind with dissolved gases. Instead, gases dissolve into and come out of solution in a linear fashion on the basis of partial pressure. Both of these factors make PFC emulsions ideal candidate compounds for reducing DCS risk and severity through elimination of N2 and improved O2 delivery.

Recently a PFC emulsion-based contrast agent for ultrasound imaging was shown to enhance N2 tissue elimination in an anesthetized swine (21). Importantly, in this model, the N2 elimination rate was highest early after administration of the PFC emulsion. The resultant decreased inert gas load could decrease the amount of bubbles formed. Given that increased bubble counts are associated with increased pulmonary artery pressure (34), the early N2 elimination with PFC would likely lead to decreased pulmonary artery pressure and a reduced incidence of cardiopulmonary DCS. This may explain the delay in onset of severe DCS observed in this study.

Mechanical vascular blockage of regional blood flow, associated bubble formation, clotting, and an inflammatory cascade compromise tissue perfusion in DCS (1). This decreased perfusion results in focal ischemia and the clinical deficits manifested in DCS. PFC compounds enhance O2 delivery in circumstances where regional blood flow is compromised, such as severe hemodilution (7) and sickle cell vascular obstruction (15). In fact, the only FDA-approved PFC emulsion was for increased regional myocardial O2 delivery in conjunction with coronary angioplasty (16). PFC's ability to increase O2 delivery is based on its O2 linear dissociation curve and small particle size. Emulsified PFC compounds can be <0.2 µm and have a limited diffusion distance unhampered by vascular obstruction (30).

Contrary to other studies (23), PFC administered before decompression (B-PFC) did not demonstrate a beneficial effect within the 2-h observation period. Because of technical limitations in overcoming the ambient pressure while animals were at saturation depth, the administration of PFC could not be completed while the animal was breathing O2. It is likely that additional inert gas was accumulated in the PFC during this time, thus negating the benefit of its N2-dissolving characteristics on ascent.

DISSUB relevance.   While there has not been a U.S. Navy DISSUB event requiring rescue since the USS Squalus (1939), preparedness presents a significant concern and logistical challenge (22). In any DISSUB scenario catastrophic enough to prevent a submarine from surfacing under its own power, increased interior air pressure is nearly inevitable. Internal compartment flooding, high-pressure air leaks from ruptured supply lines, and the use of the Emergency Air Breathing System may all increase the ambient pressure (12). Survivors in remote areas may have to wait several days for rescue, becoming saturated with inert gas and at high risk for DCS (7, 37). Furthermore, a poisonous submarine atmosphere, rapid rescue vehicle turnover (disembarking a group of survivors to load the next group), and treatment of physical injuries necessitate rapid rescue. Each of these would interfere with the ability of emergency responders to follow current Navy standards requiring >30 h to safely decompress from saturation at 132 fsw (12, 25).

The dramatic reduction in both morbidity and mortality and the increased latency of DCS onset demonstrated by the combined use of a short OPB at depth and intravenous PFC emulsion at the surface suggests that incorporating these treatment modalities into operational protocols has the potential to safely accelerate DISSUB rescue.

In conclusion, OPB at depth is effective in reducing the morbidity and mortality of severe DCS associated with direct ascent from saturation conditions. Further reductions of both morbidity and mortality were observed when OPB was combined with PFC emulsion administered on surfacing, and these beneficial effects were independent of hyperoxic seizures. We conclude that OPB at depth in combination with PFC at the surface is especially effective in reducing the morbidity and mortality of severe DCS, even when O2 exposure is sufficient to cause hyperoxic seizures. This strategy may be useful in DISSUB rescue planning and commercial diving operations.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This work was supported by NAVSEA work unit no. 63713N M000099.01B-1610.

The views expressed in this article are those of the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government. U.S. Government employees performed this work as part of their official duties; therefore, it may not be copyrighted and may be copied without restriction.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
We thank Melvin Routh, Catherine Jones, and Wayne Koller for excellent technical assistance in conducting the experiments. Thanks are also due to the staff of the Laboratory Animal Medicine and Science Department and Technical Services Department at the Naval Medical Research Center. We are also grateful to Diana Temple for thoughtful comments and assistance in preparation of this manuscript. Special thanks are extended to Bob Burge for extensive statistical analyses.


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. Temple, Undersea Medicine Dept., Naval Medical Research Center, Silver Spring, MD (e-mail: templed{at}nmrc.navy.mil)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

  1. Barratt DM, Harch PG, Van Meter K. Decompression illness in divers: a review of the literature. Neurologist 8: 186–202, 2002.[CrossRef][ISI][Medline]
  2. Behnke AR. The isobaric (oxygen window) principle of decompression. In: The New Thrust Seaward: Transactions of the Third Annual MTS Conference and Exhibit. San Diego, CA: MTS, 1967, p. 213–228.
  3. Blogg SL, Gennser M, Loveman GA, Seddon FM, Thacker JC, White MG. The effect of breathing hyperoxic gas during simulated submarine escape on venous gas emboli and decompression illness. Undersea Hyperb Med 30: 163–174, 2003.[ISI][Medline]
  4. Cabrales P, Tsai AG, Frangos JA, Briceno JC, Intaglietta M. Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons. Am J Physiol Heart Circ Physiol 287: H320–H330, 2004.[Abstract/Free Full Text]
  5. Curley MD, Ryder S, Harabin A, Weathersby P, Horn WG, Kelleher PC, Scholley B, Falloway T, Shake C, Wray DD, Lehner C, Flynn ET, Webert W, Schmidt T, Thalmann ED, Lambertsen CJ, Ball R, Francis J, McLean D, Clarke J. Medical preparedness for submarine escape and rescue. In: Medical Preparedness for Submarine Escape and Rescue, edited by Francis TJR and Curley MD. Groton, CT: Naval Submarine Medical Research Laboratory, 1997.
  6. Dromsky DM, Spiess BD, Fahlman A. Treatment of decompression sickness in swine with intravenous perfluorocarbon emulsion. Aviat Space Environ Med 75: 301–305, 2004.[Medline]
  7. Dromsky DM, Toner CB, Survanshi S, Fahlman A, Parker E, Weathersby P. Natural history of severe decompression sickness after rapid ascent from air saturation in a porcine model. J Appl Physiol 89: 791–798, 2000.[Abstract/Free Full Text]
  8. Ersoz G, Ocakcioglu B, Bastug M, Ficicilar H, Yavuzer S. Platelet aggregation and release function in hyperbaric oxygenation. Undersea Hyperb Med 25: 229–232, 1998.[ISI][Medline]
  9. Fahlman A, Kayar SR. Probabilistic modelling for estimating gas kinetics and decompression sickness risk in pigs during H2 biochemical decompression. Bull Math Biol 65: 747–766, 2003.[CrossRef][ISI][Medline]
  10. Faithfull NS. Mechanisms and efficacy of fluorochemical oxygen transport and delivery. Artif Cells Blood Substit Immobil Biotechnol 22: 181–197, 1994.[ISI][Medline]
  11. Geyer RP. Fluorocarbon-polyol artificial blood substitutes. N Engl J Med 289: 1077–1082, 1973.[ISI][Medline]
  12. Harvey CA, Stetson DM, Burns AC, Weathersby PK, Parker JW, Mole DM. Pressurized Submarine Rescue: A Manual for Undersea Medical Officers. Groton, CT: Naval Submarine Medical Research Laboratory, 1992.
  13. Hjelde A, Hjelstuen M, Haraldseth O, Martin D, Thom R, Brubakk O. Hyperbaric oxygen and neutrophil accumulation/tissue damage during permanent focal cerebral ischaemia in rats. Eur J Appl Physiol 86: 401–405, 2002.[CrossRef][ISI][Medline]
  14. Joiner JT. (Editor). Appendix VI: Saturation treatment tables. In: NOAA Diving Manual: Diving for Science and Technology. Flagstaff, AZ: NOAA, 2001.
  15. Kaul DK, Liu X, Nagel RL. Ameliorating effects of fluorocarbon emulsion on sickle red blood cell-induced obstruction in an ex vivo vasculature. Blood 98: 3128–3131, 2001.[Abstract/Free Full Text]
  16. Kerins DM. Role of the Perfluorocarbon Fluosal-DA in coronary angioplasty. Am J Med Sci 307: 218–221, 1994.[ISI][Medline]
  17. Latson G, Flynn E, Gerth W, Thalmann E, Maurer J, Lowe M. Accelerated Decompression Using Oxygen for Submarine Rescue. Summary Report and Operational Guidance (Technical Report). Panama City, FL: Navy Experimental Diving Unit, 2000.
  18. Leese PT, Noveck RJ, Shorr JS, Woods CM, Flaim KE, Keipert PE. Randomized safety studies of intravenous perflubron emulsion. I. Effects on coagulation function in healthy volunteers. Anesth Analg 91: 804–811, 2000.[Abstract/Free Full Text]
  19. Lillo RS, Himm JF, Weathersby PK, Temple DJ, Gault KA, Dromsky DM. Using animal data to improve prediction of human decompression risk following air-saturation dives. J Appl Physiol 93: 216–226, 2002.[Abstract/Free Full Text]
  20. Lowe KC. Perfluorinated blood substitutes and artificial oxygen carriers. Blood Rev 13: 171–184, 1999.[CrossRef][ISI][Medline]
  21. Lundgren C, Bergoe G, Olszowka A, Tyssebotn I. Tissue nitrogen elimination in oxygen-breathing pigs is enhanced by fluorocarbon-derived intravascular micro-bubbles. Undersea Hyperb Med 32: 215–226, 2005.[ISI][Medline]
  22. Maas P. The Rescue. New York: Harper and Row, 1967, p. 239.
  23. Mahon RT, Dainer HM, Nelson JW. Decompression sickness in a swine model: isobaric denitrogenation and perfluorocarbon at depth. Aviat Space Environ Med 77: 8–12, 2006.[Medline]
  24. Martin JD, Thom SR. Vascular leukocyte sequestration in decompression sickness and prophylactic hyperbaric oxygen therapy in rats. Aviat Space Environ Med 73: 565–569, 2002.[Medline]
  25. NAVSEA. U.S. Navy Diving Manual (Revision 4 with Change A). Washington, DC: Naval Sea Systems Command, 2001.
  26. Noveck RJ, Shannon EJ, Leese PT, Shorr JS, Flaim KE, Keipert PE, Woods CM. Randomized safety studies of intravenous perflubron emulsion. II. Effects on immune function in healthy volunteers. Anesth Analg 91: 812–822, 2000.[Abstract/Free Full Text]
  27. Parker EC, Ball R, Tibbles PM, Weathersby PK. Escape from a disabled submarine: decompression sickness risk estimation. Aviat Space Environ Med 71: 109–114, 2000.[Medline]
  28. Philp RB, Inwood MJ, Warren BA. Interactions between gas bubbles and components of the blood: implications in decompression sickness. Aerospace Med 43: 946–953, 1972.
  29. Spiess BD, McCarthy RJ, Tuman KJ, Woronowicz AW, Tool KA, Ivankovich AD. Treatment of decompression sickness with a perfluorocarbon emulsion (FC-43). Undersea Biomed Res 15: 31–37, 1988.[ISI][Medline]
  30. Symons JD, Sun X, Flaim SF, del Balzo U. Perflubron emulsion improves tolerance to low-flow ischemia in isolated rabbit hearts. J Cardiovasc Pharmacol 34: 108–115, 1999.[CrossRef][ISI][Medline]
  31. Tetzlaff K, Shank ES, Muth CM. Evaluation and management of decompression illness—an intensivist's perspective. Intensive Care Med 29: 2128–2136, 2003.[CrossRef][ISI][Medline]
  32. Thom SR, Fisher D, Zhang J, Bhopale VM, Ohnishi ST, Kotake Y, Ohnishi T, Buerk DG. Stimulation of perivascular nitric oxide synthesis by oxygen. Am J Physiol Heart Circ Physiol 284: H1230–H1239, 2003.[Abstract/Free Full Text]
  33. Thom SR, Mendiguren I, Hardy K, Bolotin T, Fisher D, Nebolon M, Kilpatrick L. Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2. Am J Physiol Cell Physiol 272: C770–C777, 1997.[Abstract/Free Full Text]
  34. Vik A, Jenssen BM, Eftedal O, Brubakk AO. Relationship between venous bubbles and hemodynamic responses after decompression in pigs. Undersea Hyperb Med 20: 233–248, 1993.[ISI][Medline]
  35. Vorosmarti J Jr, Barnard EEP, Williams J, Hanson RdG. Nitrogen elimination during steady-state hyperbaric exposures. Undersea Biomed Res 5: 243–252, 1978.[ISI][Medline]
  36. Watenpaugh DE. Degassed liquids to prevent/treat decompression sickness. Med Hypotheses 60: 720–723, 2003.[CrossRef][ISI][Medline]
  37. Weathersby PK, Survanshi SS, Parker EC, Temple DJ, Toner CB. Estimated DCS Risks In Pressurized Submarine Rescue (Technical Report). Bethesda, MD: Naval Medical Research Center, 1999.
  38. Webb JT, Pilmanis AA. A new preoxygenation procedure for extravehicular activity (EVA). Acta Astronaut 42: 115–122, 1998.[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
102/3/1099    most recent
01539.2005v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dainer, H.
Right arrow Articles by Mahon, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dainer, H.
Right arrow Articles by Mahon, R.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.