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Background: The treatment of decompression sickness (DCS) with hyperbaric oxygen (HBO2) serves to decrease intravascular bubble size, increase oxygen (O2) delivery to tissue and enhance the elimination of inert gas. Emulsified perfluorocarbons (PFC) combined with breathing O2 have been shown to have similar effects animal models. We studied an ovine model of severe DCS treated with the intravenous PFC Oxycyte™ while breathing O2 compared to saline control also breathing O2. Methods: Juvenile male sheep (N=67; weight 24.4±2.10kg) were compressed to 257 feet of sea water (fsw) in our multiple large-animal chamber where they remained under pressure for 31 minutes. Animals then were decompressed to surface pressure and randomized to receive either Oxycyte at 5mL/kg intravenously (IV) or 5mL/kg saline IV (both receiving 100% O2) 10 minutes after reaching surface pressure. Mortality was recorded at two hours, four hours, and 24 hours after receiving the study drug. Surviving animals underwent perfusion fixation and harvesting of the spinal cord at 24 hours. Spinal cord sections were assessed for volume of lesion area and compared. Results: There was no significant difference in survival at two hours (p=0.2737), four hours (p=0.2101), or 24 hours (p=0.3171). Paralysis at 24 hours was not significantly different. However, spinal cord lesion area was significantly smaller in the Oxycyte group as compared to the saline group, with median spinal cord lesion areas 0.65% vs. 0.94% (p=0.0107). Conclusion: In this ovine model of severe DCS the intravenous PFC Oxycyte did not reduce mortality but did ameliorate spinal cord injury when used after the onset of DCS.
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Doença da Descompressão/terapia , Fluorocarbonos/uso terapêutico , Oxigenoterapia/métodos , Traumatismos da Medula Espinal/prevenção & controle , Animais , Doença da Descompressão/complicações , Doença da Descompressão/mortalidade , Modelos Animais de Doenças , Fluorocarbonos/administração & dosagem , Injeções Intravenosas , Masculino , Paralisia/etiologia , Distribuição Aleatória , Solução Salina/administração & dosagem , Água do Mar , Ovinos , Traumatismos da Medula Espinal/patologia , Fatores de TempoRESUMO
PURPOSE: Perfluorocarbons (PFCs) can transport 50 times more oxygen than human plasma. Their properties may be advantageous in preservation of tissue viability in oxygen-deprived states, such as in acute lung injury. We hypothesized that an intravenous dose of the PFC emulsion Oxycyte® would improve tissue oxygenation and thereby mitigate the effects of acute lung injury. METHODS: Intravenous oleic acid (OA) was used to induce lung injury in anesthetized and instrumented Yorkshire swine assigned to three experimental groups: (1) PFC post-OA received Oxycyte® (5 ml/kg) 45 min after oleic acid-induced lung injury (OALI); (2) PFC pre-OA received Oxycyte® 45 min before OALI; and (3) Controls which received equivalent dose of normal saline. Animals were observed for 3 h after OALI began, and then euthanized. RESULTS: The median survival times for PFC post-OA, PFC pre-OA, and control were 240, 87.5, and 240 min, respectively (p = 0.001). Mean arterial pressure and mean pulmonary arterial pressure were both higher in the PFC post-OA (p < 0.001 for both parameters). Oxygen content was significantly different between PFC post-OA and the control (p = 0.001). Histopathological grading of lung injury indicated that edema and congestion was significantly less severe in the PFC post-OA compared to control (p = 0.001). CONCLUSION: The intravenous PFC Oxycyte® improves blood oxygen content and lung histology when used as a treatment after OALI, while Oxycyte® used prior to OALI was associated with increased mortality. Further exploration in other injury models is indicated.
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Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Fluorocarbonos/administração & dosagem , Oxigênio/sangue , Equilíbrio Ácido-Base , Lesão Pulmonar Aguda/induzido quimicamente , Administração Intravenosa , Animais , Pressão Arterial/efeitos dos fármacos , Gasometria , Modelos Animais de Doenças , Feminino , Fluorocarbonos/efeitos adversos , Ácido Láctico/sangue , Masculino , Ácido Oleico , Pressão Propulsora Pulmonar/efeitos dos fármacos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Índice de Gravidade de Doença , Taxa de Sobrevida , SuínosRESUMO
PURPOSE: Standard treatment for decompression sickness (DCS) is recompression therapy with hyperbaric oxygen (HBO). Non-recompressive therapies are needed to address mass casualty scenarios such as a disabled submarine rescue or DCS therapy in remote environments. Intravenously delivered perfluorocarbon (PFC) emulsions improve blood oxygen content and decrease mortality in several animal models of DCS. However, the enhanced oxygen delivery of PFC emulsions may increase CNS oxygen toxicity (seizures) risk when used in conjunction with HBO. We studied seizure latency and duration in swine randomized to receive PFC or normal saline with 6 ATA of oxygen. METHODS: Yorkshire swine (n = 31) were fitted with EEG electrodes and randomized to receive 5 ml/kg of the PFC Oxycyte (Oxygen Biotherapeutics Inc., Morrisville, NC) or saline intravenously 1 h before HBO. Unsedated animals were fitted with a snout mask for inhaled gas delivery, positioned inside the hyperbaric chamber, and compressed to 165 ft of sea water (6 ATA). After 2.5 min at 6 ATA, breathing gas was switched to 100 % O2 until signs of seizure were observed and EEG activity was evident. At seizure onset gas was switched back to air for 3 min, then the chamber was decompressed. After 24 h, the dive profile/oxygen exposure was repeated to ensure no secondary effects of PFC drug redistribution or emulsion metabolism. RESULTS/CONCLUSION: Intravenous PFC emulsion did not decrease seizure latency or increase duration on initial HBO exposure or after 24 h. This finding demonstrates the safety of PFC use in conjunction with recompression therapy to treat DCS.
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Doença da Descompressão/terapia , Fluorocarbonos/uso terapêutico , Oxigenoterapia Hiperbárica/efeitos adversos , Convulsões/tratamento farmacológico , Animais , Doença da Descompressão/fisiopatologia , Fluorocarbonos/administração & dosagem , Fluorocarbonos/efeitos adversos , Injeções Intravenosas , Masculino , Oxigênio/toxicidade , Convulsões/etiologia , Convulsões/fisiopatologia , Suínos , VigíliaRESUMO
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.
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Doença da Descompressão/prevenção & controle , Descompressão/métodos , Medicina Submarina , Animais , Doença da Descompressão/mortalidade , Intervalo Livre de Doença , Masculino , Oxigênio/administração & dosagem , Suínos , Fatores de TempoRESUMO
Decreased blood-tissue oxygenation at high altitude (HA) increases mitochondrial oxidant production and reduces exercise capacity. 5-Hydroxymethylfurfural (5-HMF) is an antioxidant that increases hemoglobin's binding affinity for oxygen. For these reasons, we hypothesized that 5-HMF would improve muscle performance in rats exposed to a simulated HA of ~5500 m. A secondary objective was to measure mitochondrial activity and dynamic regulation of fission and fusion because they are linked processes impacted by HA. Fisher 344 rats received 5-HMF (40 mg/kg/day) or vehicle during exposure to sea level or HA for 72 h. Right ankle plantarflexor muscle function was measured pre- and post-exposure. Post-exposure measurements included arterial blood gas and complete blood count, flexor digitorum brevis myofiber superoxide production and mitochondrial membrane potential (ΔΨm), and mitochondrial dynamic regulation in the soleus muscle. HA reduced blood oxygenation, increased superoxide levels and lowered ΔΨm, responses that were accompanied by decreased peak isometric torque and force production at frequencies >75 Hz. 5-HMF increased isometric force production and lowered oxidant production at sea level. In HA exposed animals, 5-HMF prevented a decline in isometric force production at 75-125 Hz, prevented an increase in superoxide levels, further decreased ΔΨm, and increased mitochondrial fusion 2 protein expression. These results suggest that 5-HMF may prevent a decrease in hypoxic force production during submaximal isometric contractions by an antioxidant mechanism.
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Antioxidantes , Superóxidos , Ratos , Animais , Superóxidos/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Músculo Esquelético/metabolismo , Hipóxia/metabolismo , Oxidantes/farmacologiaRESUMO
BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.
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Doença da Descompressão , Mergulho , Oxigenoterapia Hiperbárica , Doenças da Medula Espinal , Animais , Descompressão , Doença da Descompressão/terapia , Hélio , Nitrogênio , Oxigênio , Doenças da Medula Espinal/terapia , SuínosRESUMO
Positive end-expiratory pressure (PEEP) is a respiratory/ventilation procedure that is used to maintain or improve breathing in clinical and experimental cases that exhibit impaired lung function. Body fluid shift movement is not monitored during PEEP application in intensive care units (ICU), which would be interesting specifically in hypotensive patients. Brain injured and hypotensive patients are known to have compromised cerebral blood flow (CBF) autoregulation (AR) but currently, there is no non-invasive way to assess the risk of implementing a hypotensive resuscitation strategy and PEEP use in these patients. The advantage of electrical bioimpedance measurement is that it is noninvasive, continuous, and convenient. Since it has good time resolution, it is ideal for monitoring in intensive care units (ICU). The basis of its future use is to establish physiological correlates. In this study, we demonstrate the use of electrical bioimpedance measurement during bleeding and the use of PEEP in pig measurement. In an anesthetized pig, we performed multimodal recording on the torso and head involving electrical bioimpedance spectroscopy (EIS), fixed frequency impedance plethysmography (IPG), and bipolar (rheoencephalography - REG) measurements and processed data offline. Challenges (n=16) were PEEP, bleeding, change of SAP, and CO2 inhalation. The total measurement time was 4.12 hours. Systemic circulatory results: Bleeding caused a continuous decrease of SAP, cardiac output (CO), and increase of heart rate, temperature, shock index (SI), vegetative - Kerdo index (KI). Pulse pressure (PP) decreased only after second bleeding which coincided with loss of CBF AR. Pulmonary arterial pressure (PAP) increased during PEEP challenges as a function of time and bleeding. EIS/IPG results: Body fluid shift change was characterized by EIS-related variables. Electrical Impedance Spectroscopy was used to quantify the intravascular, interstitial, and intracellular volume changes during the application of PEEP and simulated hemorrhage. The intravascular fluid compartment was the primary source of blood during hemorrhage. PEEP produced a large fluid shift out of the intravascular compartment during the first bleeding period and continued to lose more blood following the second and third bleeding. Fixed frequency IPG was used to quantify the circulatory responses of the calf during PEEP and simulated hemorrhage. PEEP reduced the arterial blood flow into the calf and venous outflow from the calf. Head results: CBF AR was evaluated as a function of SAP change. Before bleeding, and after moderate bleeding, intracranial pressure (ICP), REG, and carotid flow pulse amplitudes (CFa) increased. This change reflected vasodilatation and active CBF AR. After additional hemorrhaging during PEEP, SAP, ICP, REG, CFa signal amplitudes decreased, indicating passive CBF AR. 1) The indicators of active AR status by modalities was the following: REG (n=9, 56 %), CFa (n=7, 44 %), and ICP (n=6, 38 %); 2) CBF reactivity was better for REG than ICP; 3) REG and ICP correlation coefficient were high (R2 = 0.81) during CBF AR active status; 4) PRx and REGx reflected active CBF AR status. CBF AR monitoring with REG offers safety for patients by preventing decreased CBF and secondary brain injury. We used different types of bioimpedance instrumentation to identify physiologic responses in the different parts of the body (that have not been discussed before) and how the peripheral responses ultimately lead to decreased cardiac output and changes in the head. These bioimpedance methods can improve ICU monitoring, increase the adequacy of therapy, and decrease mortality and morbidity.
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INTRODUCTION: The use of hyperbaric oxygen (HBO) to expedite decompression from saturation has not been proven and may increase risk of toxicity to the pulmonary system. To evaluate any benefit of HBO during decompression, we used a 70-kg swine model of saturation and examined lung tissue by microarray analysis for evidence of RNA regulation. METHODS: Unrestrained, non-sedated swine were compressed to 132 fsw (5 ATA) for 22 h to achieve saturation. Animals then underwent decompression on air (AirD) or HBO (HBOD) starting at 45 fsw (2.36 ATA). Animals were evaluated for Type I and Type II decompression sickness (DCS) for 24 h. Control (SHAM) animals were placed in the chamber for the same duration, but were not compressed. Animals were sacrificed 24 h after exposure and total RNA was isolated from lung samples for microarray hybridizations on the Affymetrix platform. RESULTS: There was no evidence of Type I DCS or severe cardiopulmonary DCS in any of the animals; abnormal gaits were noted only in the HBOD group (4/9).Three genes (nidogen 2, calcitonin-like receptor, and pentaxin-related gene) were significantly up-regulated in both the AirD and HBOD groups compared to controls. Three other genes (TN3, platelet basic protein, and cytochrome P450) were significantly down-regulated in both groups. CONCLUSIONS: HBO during decompression from saturation did not reduce the incidence of DCS. Gene regulation was apparent and similar in both the AirD and HBOD groups, particularly in genes related to immune function and cell signaling.
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Doença da Descompressão/prevenção & controle , Regulação da Expressão Gênica , Oxigenoterapia Hiperbárica , Consumo de Oxigênio , RNA , Animais , Doença da Descompressão/etiologia , Doença da Descompressão/genética , Pulmão/química , Masculino , Modelos Animais , Análise de Sequência com Séries de Oligonucleotídeos , RNA/química , RNA/isolamento & purificação , SuínosRESUMO
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.
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Doença da Descompressão/prevenção & controle , Descompressão/métodos , Oxigênio/administração & dosagem , Animais , Doença da Descompressão/fisiopatologia , Masculino , SuínosRESUMO
INTRODUCTION: Decompression sickness (DCS) occurs when bubbles form due to pressure decreases with severity ranging from trivial to fatal. Standard treatment requires a hyperbaric chamber, not likely to be available at remote sites or during a disabled submarine escape or rescue. Alternative (non-recompressive) treatments are needed. Intravenous administration of emulsified perfluorocarbons (PFCs) enhances oxygen delivery to, and inert gas removal from, tissues. Swine studies show PFCs administered with supplemental oxygen before symptom onset can decrease DCS incidence. We used a swine model to test whether PFC plus supplemental oxygen could improve outcome when infused after DCS symptom onset. METHODS: After rapid decompression from 31 min at 200 fsw (7.06 ATA) animals were observed for signs of DCS. Upon DCS onset animals received 100% 02 and were randomized to receive either saline or PFC. Oxygen administration was continued for 1 h and the primary outcomes of mortality and/or abnormal gait were noted 24 h after surfacing. RESULTS: PFC significantly improved survival, with 18/25 (72%) PFC treated animals and 13/29 (45%) saline treated animals alive at 24 h post-exposure. Objective measures of stance/gait trended toward improvement; spinal cord lesions correlated with severity of stance/gait abnormalities. CONCLUSION: PFC administered after DCS onset improved survival in this 20-kg swine model. Further study into the mechanisms of benefit and delayed DCS therapy are warranted.
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Doença da Descompressão/tratamento farmacológico , Fluorocarbonos/uso terapêutico , Animais , Doença da Descompressão/mortalidade , Doença da Descompressão/prevenção & controle , Masculino , Condicionamento Físico Animal , Distribuição Aleatória , Medula Espinal/patologia , Traumatismos da Medula Espinal , Suínos , Fatores de Tempo , Estados UnidosRESUMO
Dysautonomia has been observed in many cardiac diseases; however, its effect in decompression sickness (DCS) has not been well examined largely due to the difficulty in obtaining experimental data in human or animal subjects. In this study, we examine how DCS affects the autonomic nervous system's (ANS) dynamics in swine. Baseline and post-DCS electrocardiograms were obtained via telemetry recordings and compared. These data were analyzed using both the power spectrum method and our recently developed principal dynamic mode (PDM) analysis. PDM is able to separate the dynamic tones of the sympathetic and parasympathetic nervous systems. Both methods demonstrated a statistically significant decrease (>55%; P < 0.05) in the dynamics of both branches of the autonomic nervous system in the swine with DCS compared with the control condition. In cardiac diseases such as myocardial infarction, ANS imbalance is often associated with a significant increase in sympathetic tone, which may or may not be counterbalanced by parasympathetic nervous activity. However, the effect of DCS is such that both branches of the ANS are depressed >55% compared with the control condition, suggesting impairment, but not imbalance, of the ANS.
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Sistema Nervoso Autônomo/fisiopatologia , Doença da Descompressão/fisiopatologia , Coração/fisiologia , Suínos/fisiologia , Animais , Doença da Descompressão/etiologia , Modelos Animais de Doenças , Eletrocardiografia , Marcha/fisiologia , Coração/inervação , Sistema de Condução Cardíaco , Frequência Cardíaca/fisiologia , Masculino , Modelos Neurológicos , Dinâmica não Linear , Análise de Componente Principal , TelemetriaRESUMO
INTRODUCTION: Perfluorocarbons (PFC) are fluorinated hydrocarbons that dissolve gases to a much greater degree than plasma and hold promise in treating decompression sickness (DCS). The efficacy of PFC in a mixed gender model of DCS and safety in recompression therapy has not been previously explored. METHODS: Swine (25 kg; N = 104; 51 male and 53 female) were randomized into normal saline solution (NSS) or PFC emulsion treatment groups and subjected to compression on air in a hyperbaric chamber at 200 fsw for 31 min. Then the animals were decompressed and observed for signs of DCS. Afterwards, they were treated with oxygen and either PFC (4 cc · kg-1) or NSS (4 cc · kg-1). Surviving animals were observed for 4 h, at which time they underwent recompression therapy using a standard Navy Treatment Table 6. After 24 h the animals were assessed and then euthanized. RESULTS: Survival rates were not significantly different between NSS (74.04%) and PFC (66.67%) treatment groups. All swine that received recompression treatment survived to the end of the study and no seizures were observed in either PFC or NSS animals. Within the saline treated swine group there were no significant differences in DCS survival between male (75.00%, N = 24) and female (73.08%, N = 26) swine. Within the PFC treated swine, survival of females (51.85%, N = 27) was significantly lower than males (81.48%, N = 27). DISCUSSION: In this large animal mixed gender efficacy study in DCS, PFC did not improve mortality or spinal cord injury, but appears safe during recompressive therapy. Gender differences in DCS treatment with PFC will need further study.Cronin WA, Hall AA, Auker CR, Mahon RT. Perfluorocarbon in delayed recompression with a mixed gender swine model of decompression sickness. Aerosp Med Hum Perform. 2018; 89(1):14-18.
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Doença da Descompressão/mortalidade , Doença da Descompressão/terapia , Descompressão/métodos , Fluorocarbonos/uso terapêutico , Animais , Modelos Animais de Doenças , Feminino , Masculino , Traumatismos da Medula Espinal , SuínosRESUMO
Introduction: Individuals with a known susceptibility to high altitude pulmonary edema (HAPE) demonstrate a reduced ventilation response and increased pulmonary vasoconstriction when exposed to hypoxia. It is unknown whether reduced sensitivity to hypercapnia is correlated with increased incidence and/or severity of HAPE, and while acute exercise at altitude is known to exacerbate symptoms the effect of exercise training on HAPE susceptibility is unclear. Purpose: To determine if chronic intermittent hypercapnia and exercise increases the incidence of HAPE in rats. Methods: Male Wistar rats were randomized to sedentary (sed-air), CO2 (sed-CO2,) exercise (ex-air), or exercise + CO2 (ex-CO2) groups. CO2 (3.5%) and treadmill exercise (15 m/min, 10% grade) were conducted on a metabolic treadmill, 1 h/day for 4 weeks. Vascular reactivity to CO2 was assessed after the training period by rheoencephalography (REG). Following the training period, animals were exposed to hypobaric hypoxia (HH) equivalent to 25,000 ft for 24 h. Pulmonary injury was assessed by wet/dry weight ratio, lung vascular permeability, bronchoalveolar lavage (BAL), and histology. Results: HH increased lung wet/dry ratio (HH 5.51 ± 0.29 vs. sham 4.80 ± 0.11, P < 0.05), lung permeability (556 ± 84 u/L vs. 192 ± 29 u/L, P < 0.001), and BAL protein (221 ± 33 µg/ml vs. 114 ± 13 µg/ml, P < 0.001), white blood cell (1.16 ± 0.26 vs. 0.66 ± 0.06, P < 0.05), and platelet (16.4 ± 2.3, vs. 6.0 ± 0.5, P < 0.001) counts in comparison to normobaric normoxia. Vascular reactivity was suppressed by exercise (-53% vs. sham, P < 0.05) and exercise+CO2 (-71% vs. sham, P < 0.05). However, neither exercise nor intermittent hypercapnia altered HH-induced changes in lung wet/dry weight, BAL protein and cellular infiltration, or pulmonary histology. Conclusion: Exercise training attenuates vascular reactivity to CO2 in rats but neither exercise training nor chronic intermittent hypercapnia affect HH- induced pulmonary edema.
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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.
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Antagonistas Adrenérgicos beta/uso terapêutico , Doença da Descompressão/prevenção & controle , Propranolol/uso terapêutico , Animais , Doença da Descompressão/etiologia , Modelos Animais de Doenças , Mergulho , Frequência Cardíaca , Masculino , Oxigenoterapia , Suínos , Fatores de TempoRESUMO
INTRODUCTION: Disabled submarine survivors could achieve inert gas tissue saturation likely to cause severe decompression sickness (DCS) on surfacing. This risk increases with time and depth of exposure. Methods to reduce DCS risk and severity are needed specifically for such an operational scenario. METHODS: Yorkshire swine (16.2-26.6 kg) fitted with an external jugular catheter were compressed to 5 ATA for 22 h. They then received an enriched breathing mix of 44% N2 and 56% O2, and an infusion of either saline or a perfluorocarbon (PFC) emulsion, and were observed for 2 h before surfacing without decompression stops. Controls were surfaced after 22 h saturation at 5 ATA. Surface observations continued for another 2 h on all animals and signs of DCS were recorded to the nearest minute. RESULTS: Seizure activity at depth was noted in 0/26 controls, 1/16 in the saline group, and 7/16 in the PFC group. DCS in < 2 h occurred in 25/26 air controls, 2/15 in the enriched mix/saline group, and 4/9 not suffering seizure in the enriched mix/PFC group. Death in < 2 h occurred in 23/26 controls, 1/15 in the saline group, and 1/9 in the PFC group. DISCUSSION/CONCLUSION: This study demonstrates the benefits of breathing increased O2 at depth prior to rapid decompression and the deleterious effects of PFC administration at depth in a swine saturation model with rapid decompression. Future studies should examine a minimal O2 pre-breathe period to offer protection against DCS as well as the role of PFC use after surfacing.
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Doença da Descompressão/terapia , Fluorocarbonos/administração & dosagem , Nitrogênio/administração & dosagem , Oxigênio/administração & dosagem , Animais , Descompressão , Modelos Animais de Doenças , Emulsões , Infusões Intravenosas , Masculino , Convulsões/etiologia , Suínos , Redução de PesoRESUMO
One of the causes of diffuse pulmonary infiltrates can be blood from diffuse alveolar hemorrhage. Other causes include malignancy, edema fluid, infections, and protein (blood, pus, water, cells, or protein). Autoimmune vasculitis, such as Wegener's granulomatosis, should be considered in the setting of diffuse pulmonary infiltrates, anemia, systemic symptoms, and recurrence despite antibiotic therapy. Antineutrophilic cytoplasmic antibody testing can be useful but is not always diagnostic. Early tissue biopsy should be considered to guide therapy. We present a case of Wegener's granulomatosis that presented with diffuse alveolar hemorrhage. Diagnosis was made through renal biopsy; however, antineutrophilic cytoplasmic antibody testing was negative. A brief overview of pulmonary-renal vasculitides is also presented.
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Granulomatose com Poliangiite/diagnóstico , Hemotórax/diagnóstico , Alvéolos Pulmonares/patologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Biomarcadores , Biópsia , Diagnóstico Diferencial , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico por imagem , Hemoptise/complicações , Hemoptise/diagnóstico , Hemotórax/complicações , Hemotórax/diagnóstico por imagem , Humanos , Rim/patologia , Masculino , Alvéolos Pulmonares/diagnóstico por imagem , RadiografiaRESUMO
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 (nâ=â50) were fitted with a vascular port, recovered, randomized, and compressed to 180 feet of sea water (fsw) for 31âmin followed by decompression at 30âfsw/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 1âh before compression and 1, 24, 48, 96, 168 and 192âh after treatment. No significant changes in normalized platelet counts were observed. Prothrombin time was elevated in DCS-PFC from 48 to 192âh compared with DCS-NS, and from 96 to 192âh compared with Sham-PFC. Normalized activated partial thromboplastin time was also elevated in DCS-PFC from 168 to 192âh 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.
Assuntos
Plaquetas/efeitos dos fármacos , Doença da Descompressão/tratamento farmacológico , Fluorocarbonos/farmacologia , Oxigênio/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Animais , Plaquetas/patologia , Doença da Descompressão/sangue , Doença da Descompressão/fisiopatologia , Modelos Animais de Doenças , Emulsões , Humanos , Infusões Intravenosas , Masculino , Orquiectomia , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Tempo de Protrombina , SuínosRESUMO
BACKGROUND: There is inadequate information on the physiologic effects of aeromedical evacuation on wounded war fighters with traumatic brain injury (TBI). At altitudes of 8,000 ft, the inspired oxygen is lower than standard sea level values. In troops experiencing TBI, this reduced oxygen may worsen or cause secondary brain injury. We tested the hypothesis that the effects of prolonged aeromedical evacuation on critical neurophysiologic parameters (i.e., brain oxygenation [PbtO2]) of swine with a fluid percussion injury/TBI would be detrimental compared with ground (normobaric) transport. METHODS: Yorkshire swine underwent fluid percussion injury/TBI with pretransport stabilization before being randomized to a 4-hour aeromedical transport at simulated flight altitude of 8,000 ft (HYPO, n = 8) or normobaric ground transport (NORMO, n = 8). Physiologic measurements (i.e., PbtO2, cerebral perfusion pressure, intracranial pressure, regional cerebral blood flow, mean arterial blood pressure, and oxygen transport variables) were analyzed. RESULTS: Survival was equivalent between groups. Measurements were similar in both groups at all phases up to and including onset of flight. During the flight, PbtO2, cerebral perfusion pressure, and mean arterial blood pressure were significantly lower in the HYPO than in the NORMO group. At the end of flight, regional cerebral blood flow was lower in the HYPO than in the NORMO group. Other parameters such as intracranial pressure, cardiac output, and mean pulmonary artery pressure were not significantly different between the two groups. CONCLUSION: A 4-hour aeromedical evacuation at a simulated flight altitude of 8,000 ft caused a notable reduction in neurophysiologic parameters compared with normobaric conditions in this TBI swine model. Results suggest that hypobaric conditions exacerbate cerebral hypoxia and may worsen TBI in casualties already in critical condition.
Assuntos
Resgate Aéreo , Altitude , Lesões Encefálicas Traumáticas/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Animais , Lesões Encefálicas Traumáticas/mortalidade , Débito Cardíaco , Circulação Cerebrovascular , Modelos Animais de Doenças , Hipóxia Encefálica/mortalidade , Pressão Intracraniana , Oxigênio/sangue , Distribuição Aleatória , Taxa de Sobrevida , SuínosRESUMO
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.
Assuntos
Doença da Descompressão/tratamento farmacológico , Doença da Descompressão/mortalidade , Fluorocarbonos/uso terapêutico , Animais , Modelos Animais de Doenças , Fluorocarbonos/efeitos adversos , Fígado/patologia , Masculino , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Taxa de SobrevidaRESUMO
INTRODUCTION: Exercise-induced bronchoconstriction (EIB) is present in 40 to 90% of patients with asthma. Exhaled NO (eNO) levels have been correlated with bronchial hyperresponsiveness to methacholine, and have correlated with the degree of decrease in FEV(1) with exercise. The purpose of our study was to examine whether eNO measurements prior to or after exercise could be used as a surrogate marker of exertional bronchoconstriction in a population referred specifically for the evaluation of EIB. METHODS: We studied 50 consecutive subjects without a history of asthma who were referred for the clinical evaluation of EIB. eNO levels were measured prior to exercise challenge and every 5 min for a total of 30 min after exercise. Forced expiratory flows were measured prior to and serially after exercise challenge. RESULTS: Seven subjects had a decrease in FEV(1) of > or = 15% with exercise. The mean eNO level prior to exercise was 41 parts per billion (ppb) [median +/- SD, 23 +/- 42.2 ppb] in the EIB group and 25.6 ppb (median, 19.95 +/- 18.47 ppb) in the group without EIB. A receiver operator characteristic curve yielded a value of 0.636. When using an eNO level of < 12 ppb, the sensitivity, specificity, negative predictive value, and positive predictive value for EIB were 1.0, 0.31, 0.19, and 1.0, respectively; therefore, no one with a baseline eNO of < 12 ppb demonstrated EIB. CONCLUSIONS: No subjects with very low pre-exercise eNO levels (< 12 ppb) demonstrated bronchial hyperresponsiveness to exercise. eNO measurement may obviate the need for bronchoprovocation testing in patients who complain of exertional dyspnea.