Propranolol Effects on Decompression Sickness in a Simulated DISSUB Rescue in Swine.

INTRODUCTION: Disabled submarine (DISSUB) survivors may face elevated CO2 levels and inert gas saturation, putting them at risk for CO2 toxicity and decompression sickness (DCS). Propranolol was shown to reduce CO2 production in an experimental DISSUB model in humans but its effects on DCS in a DISSUB rescue scenario are unknown. A 100% oxygen prebreathe (OPB) reduces DCS incidence and severity and is incorporated into some DISSUB rescue protocols. We used a swine model of DISSUB rescue to study the effect of propranolol on DCS incidence and mortality with and without an OPB. METHODS: In Experiment 1, male Yorkshire Swine (70 kg) were pressurized to 2.8 ATA for 22 h. Propranolol 1.0 mg · kg-1 (IV) was administered at 21.25 h. At 22 h, the animal was rapidly decompressed and observed for DCS type, onset time, and mortality. Experimental animals (N = 21; 69 ± 4.1 kg), PROP1.0, were compared to PROP1.0-OPB45 (N = 8; 69 ± 2.8 kg) with the same dive profile, except for a 45 min OPB prior to decompression. In Experiment 2, the same methodology was used with the following changes: swine pressurized to 2.8 ATA for 28 h; experimental group (N = 25; 67 ± 3.3 kg), PROP0.5 bis, propranolol 0.5 mg · kg-1 bis (twice) (IV) was administered at 22 h and 26 h. Control animals (N = 25; 67 ± 3.9 kg) received normal saline. RESULTS: OPB reduced mortality in PROP1.0-OBP45 compared to PROP1.0 (0% vs. 71%). PROP0.5 bis had increased mortality compared to CONTROL (60-% vs. 4%). DISCUSSION: Administration of beta blockers prior to saturation decompression appears to increase DCS and worsen mortality in a swine model; however, their effects in bounce diving remain unknown.Forbes AS, Regis DP, HallAA, Mahon RT, Cronin WA. Propranolol effects on decompression sickness in a simulated DISSUB rescue in swine. Aerosp Med Hum Perform. 2017; 88(4):385-391.

Safety of antimalarial medications for use while scuba diving in malaria Endemic Regions.

BACKGROUND: Recreational diving occurs annually in areas of the world where malaria is endemic. The safety and efficacy of antimalarials for travelers in a hyperbaric environment is unknown. Of particular concern would be medications with adverse effects that could either mimic diving related illnesses such as barotrauma, decompression sickness (DCS) and gas toxicities, or increase the risk for such illnesses. METHODS: We conducted a review of PubMed and Cochrane databases to determine rates of neurologic adverse effects or other effects from antimalarials that may be a problem in the diving environment. RESULTS: One case report was found on diving and mefloquine. Multiple case reports and clinical trials were found describing neurologic adverse effects of the major chemoprophylactic medications atovaquone/proguanil, chloroquine, doxycycline, mefloquine, and primaquine. CONCLUSIONS: Of the available literature, atovaquone/proguanil and doxycycline are most likely the safest agents and should be preferred; atovaquone/proguanil is superior due to reduced rates of sunburn in the marine environment. Primaquine also appears to be safe, but has reduced efficacy against P. falciparum; mefloquine possesses the highest rate of neurologic side effects and therefore these agents should be limited to extreme cases of patients intolerant to other agents. Chloroquine appears unsafe in the hyperbaric environment and should be avoided. More studies are required to include database reviews of returned divers traveling to malaria endemic areas and randomized controlled trials in the hyperbaric environments.

The effect of the perfluorocarbon emulsion Oxycyte on platelet count and function in the treatment of decompression sickness in a swine model.

Decompression from elevated ambient pressure is associated with platelet activation and decreased platelet counts. Standard treatment for decompression sickness (DCS) is hyperbaric oxygen therapy. Intravenous perfluorocarbon (PFC) emulsion is a nonrecompressive therapy being examined that improves mortality in animal models of DCS. However, PFC emulsions are associated with a decreased platelet count. We used a swine model of DCS to study the effect of PFC therapy on platelet count, function, and hemostasis. Castrated male swine (n = 50) were fitted with a vascular port, recovered, randomized, and compressed to 180 feet of sea water (fsw) for 31 min followed by decompression at 30 fsw/min. Animals were observed for DCS, administered 100% oxygen, and treated with either emulsified PFC Oxycyte (DCS-PFC) or isotonic saline (DCS-NS). Controls underwent the same procedures, but were not compressed (Sham-PFC and Sham-NS). Measurements of platelet count, thromboelastometry, and coagulation were obtained 1 h before compression and 1, 24, 48, 96, 168 and 192 h after treatment. No significant changes in normalized platelet counts were observed. Prothrombin time was elevated in DCS-PFC from 48 to 192 h compared with DCS-NS, and from 96 to 192 h compared with Sham-PFC. Normalized activated partial thromboplastin time was also elevated in DCS-PFC from 168 to 192 h compared with Sham-PFC. No bleeding events were noted. DCS treated with PFC (Oxycyte) does not impact platelet numbers, whole blood clotting by thromboelastometry, or clinical bleeding. Late changes in prothrombin time and activated partial thromboplastin time associated with PFC use in both DCS therapy and controls warrant further investigation.

Dodecafluoropentane (DDFPe) and decompression sickness-related mortality in rats.

INTRODUCTION: Perfluorocarbon (PFC) formulations can be a useful adjunct treatment for decompression sickness (DCS) when staged decompression procedures cannot be followed due to time constraints or lack of equipment. The benefit of PFC treatment is believed to result from its ability to transport more dissolved gas than can be transported by blood alone. Dodecylfluoropentane (DDFPe) is a unique nanodroplet compound that expands into a gaseous state when exposed to physiological temperatures, resulting in a higher dissolved gas-carrying capacity than standard PFC formulations. METHODS: We investigated the efficacy of DDFPe in reducing morbidity and mortality in a rat model of severe DCS. Male Sprague-Dawley rats (250-280 g) were compressed to 210 fsw for 60 min before rapid decompression. Animals were immediately injected with 2% DDFPe (0.07 ml · kg(-1), 0.5 ml · kg(-1), 1.0 ml · kg(-1)) or saline, and were transferred to a 100% O2 environment for 30 min. RESULTS: Of the animals in the saline group, 47% (18/38) did not survive the decompression event, while ~98% (46/47) of the animals in the DDFPe group did not survive. Of the animals that died during the observation period, the saline group survived on average 89% longer than DDFPe treated animals. Seizures occurred in 42% of the DDFPe group vs. 16% in the saline group. Histological analysis revealed the presence of large, multifocal gas emboli in the liver and heart of DDFPe treated animals. CONCLUSIONS: We conclude that DDFPe is not an effective nonrecompressive treatment for DCS in rodents. Sheppard RL, Regis DP, Mahon RT. Dodecafluoropentane (DDFPe) and decompression sickness-related mortality in rats.

Decompression and decompression sickness.

The ever-present desire of humankind to explore new limits introduced us to the syndrome of decompression sickness (DCS). This broad overview of DCS is aimed at its pathophysiology and basics of therapeutic strategies. After a brief explanation of decompression theory, historical vignettes will serve to inform the practical application of our increasing understanding of DCS risks. The pathophysiology, current practices, role of bubble monitoring, risk factors, and potential long-term effects of DCS are also discussed. The goal is to explain the current state of DCS understanding in the context of a robust observational and empirical history. However, DCS remains a syndrome consisting of a constellation of symptoms following a change in ambient pressure. Though great strides have been made, significant knowledge gaps remain. If the coming years advance the field even a fraction of what its predecessors accomplished, the health and safety of those who endeavor in the environment of changing pressures most certainly will be improved.

Interrupted oxygen pre-breathing and decompression outcomes in swine.

BACKGROUND: Rescue from a disabled submarine may result in substantial risk for severe decompression sickness (DCS) among survivors. Oxygen prebreathe (OPB) before rapid decompression has been shown to significantly reduce risk or delay onset for severe DCS in animals. However, the duration of this benefit remains unknown and might even be lost if a delay between the prebreathe period to initiation of recompression therapy allows for nitrogen reaccumulation. METHODS: We hypothesized that the benefit of OPB would be lost following subsequent periods of air interruption in a 70-kg swine saturation model. Following OPB of 45 or 60 min with varying periods (30, 45, 60 min) of air interruption, 61 swine exposed to 2.7 ATA for 22 h were rapidly decompressed. Swine without OPB served as negative controls and swine treated with 45 min of OPB without air interruption served as positive controls. RESULTS: Comparing experimental groups for Type II DCS incidence showed OPB120/60 being the only experimental group (11%) statistically different than the negative control group OPB0 (80%). Log rank tests comparing Type II DCS free survival only showed statistically significant differences for OPB45/60 compared to positive control group OPB45, while, more importantly, demonstrating a significant difference for OPB120/60 compared to that approximated for OPB45, indicating a significant reversal of the air interruption effects with longer OPB on Type II DCS disease free survival. DISCUSSION: Based on these findings we concluded that the protective effects of OPB against severe DCS are reduced with increasing periods of air interruption.

Transcriptionally active PCR for antigen identification and vaccine development: in vitro genome-wide screening and in vivo immunogenicity.

We have evaluated a technology called transcriptionally active PCR (TAP) for high throughput identification and prioritization of novel target antigens from genomic sequence data using the Plasmodium parasite, the causative agent of malaria, as a model. First, we adapted the TAP technology for the highly AT-rich Plasmodium genome, using well-characterized P. falciparum and P. yoelii antigens and a small panel of uncharacterized open reading frames from the P. falciparum genome sequence database. We demonstrated that TAP fragments encoding six well-characterized P. falciparum antigens and five well-characterized P. yoelii antigens could be amplified in an equivalent manner from both plasmid DNA and genomic DNA templates, and that uncharacterized open reading frames could also be amplified from genomic DNA template. Second, we showed that the in vitro expression of the TAP fragments was equivalent or superior to that of supercoiled plasmid DNA encoding the same antigen. Third, we evaluated the in vivo immunogenicity of TAP fragments encoding a subset of the model P. falciparum and P. yoelii antigens. We found that antigen-specific antibody and cellular immune responses induced by the TAP fragments in mice were equivalent or superior to those induced by the corresponding plasmid DNA vaccines. Finally, we developed and demonstrated proof-of-principle for an in vitro humoral immunoscreening assay for down-selection of novel target antigens. These data support the potential of a TAP approach for rapid high throughput functional screening and identification of potential candidate vaccine antigens from genomic sequence data.