Richard T. Mahon

Impairment of the autonomic nervous function during decompression sickness in swine

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 systems (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.

Intravenous Perfluorocarbon After Onset of Decompression Sickness Decreases Mortality in 20-kg Swine

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.

Evaluation of chest seal performance in a swine model Comparison of Asherman vs. Bolin seal

INTRODUCTION Chest seals are externally applied devices used to treat an open pneumothorax. There is concern that chest seals used for treatment of an open pneumothorax can fail due to coagulation or malfunction of the external vent and poor skin adherence. Chest seal failure may lead to respiratory compromise or the development of a tension pneumothorax. The objective of this project was to compare the efficacy and adhesive capacity of two chest seals: Asherman and Bolin. METHODS An open pneumothorax model in the swine (30 kg) was developed to test the performance of Asherman (n=8) and Bolin (n=8) seals based on haemodynamic and ultrasonographic changes following intrathoracic air and blood infusion. Seal adherence measured on a scale from 0 (poor) to 3 (good) was tested on dry skin and skin soiled with blood. RESULTS After standardised perforation of the chest cavity and aperture blocking, an air infusion of 372 (S.D. 214 ml) was sufficient to reduce mean arterial pressure (MAP) by 20%. Both chest seals prevented a significant fall in MAP after infusion of 1500 ml air into the chest cavity, and had similar adherence scores (2.6 (S.D. 0.8) and 2.8 (S.D. 0.6)) on dry skin. However, on blood soiled skin the Bolin seal had a higher score (2.7 (S.D. 0.6) vs. 0.4 (S.D. 0.7); p<0.01). Ultrasound did not yield interpretable results to differentiate between Asherman and Bolin seals. CONCLUSIONS The Bolin and Asherman chest seals were equivalent in preventing the development of a tension pneumothorax in this open pneumothorax model. However, the Bolin chest seal demonstrated stronger adherence in blood soiled conditions.

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.

Brain oxygenation and CNS oxygen toxicity after infusion of perfluorocarbon emulsion

Intravenous perfluorocarbon (PFC) emulsions, administered with supplemental inspired O(2), are being evaluated for their ability to eliminate N(2) from blood and tissue prior to submarine escape, but these agents can increase the incidence of central nervous system (CNS) O(2) toxicity, perhaps by enhancing O(2) delivery to the brain. To assess this, we infused a PFC emulsion (Oxycyte, 6 ml/kg iv) into anesthetized rats and measured cerebral Po(2) and regional cerebral blood flow (rCBF) in cortex, hippocampus, hypothalamus, and striatum with 100% O(2) at 1, 3, or 5 atmospheres absolute (ATA). At 1 ATA, brain Po(2) stabilized at >20 mmHg higher in animals infused with PFC emulsion than in control animals infused with saline, and rCBF fell by ~10%. At 3 ATA, PFC emulsion raised brain Po(2) >70 mmHg above control levels, and rCBF decreased by as much as 25%. At 5 ATA, brain Po(2) was ≥159 mmHg above levels in control animals for the first 40 min but then rose sharply; rCBF showed a similar profile, reflecting vasoconstriction followed by hyperemia. Conscious rats were also pretreated with PFC emulsion at 3 or 6 ml/kg iv and exposed to 100% O(2) at 5 ATA. At the lower dose, 80% of the animals experienced seizures by 33 min compared with 50% of the control animals. At the higher dose, seizures occurred in all rats within 25 min. At these doses, administration of PFC emulsion poses a clear risk of CNS O(2) toxicity in conscious rats exposed to hyperbaric O(2) at 5 ATA.

Oxygen Breathing Accelerates Decompression from Saturation at 40 msw in 70-kg Swine

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.

Brain hypoxia is exacerbated in hypobaria during aeromedical evacuation in swine with traumatic brain injury.

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.

Vigabatrin prevents seizure in swine subjected to hyperbaric hyperoxia

Oxygen is the most widely used therapeutic strategy to prevent and treat decompression sickness (DCS). Oxygen prebreathe (OPB) eliminated DCS in 20-kg swine after rapid decompression from saturation at 60 feet of seawater (fsw). However, hyperbaric oxygen (HBO) has risks. As oxygen partial pressure increases, so do its toxic effects. Central nervous system (CNS) oxygen toxicity is the most severe side effect, manifesting as seizure. An adjunctive therapeutic is needed to extend OPB strategies to deeper depths and prevent/delay seizure onset. The Food and Drug Administration-approved anti-epileptic vigabatrin has prevented HBO-induced seizures in rats up to 132 fsw. This study aimed to confirm the rat findings in a higher animal model and determine whether acute high-dose vigabatrin evokes retinotoxicity symptoms seen with chronic use clinically in humans. Vigabatrin dose escalation studies were conducted 20-kg swine exposed to HBO at 132 or 165 fsw. The saline group had seizure latencies of 7 and 11 min at 165 and 132 fsw, respectively. Vigabatrin at 180 mg/kg significantly increased latency (13 and 27 min at 165 and 132 fsw, respectively); 250 mg/kg abolished seizure activity at all depths. Functional electroretinogram and histology of the retinas showed no signs of retinal toxicity in any of the vigabatrin=treated animals. In the 250 mg/kg group there was no evidence of CNS oxygen toxicity; however, pulmonary oxygen toxicity limited HBO exposure. Together, the findings from this study show that vigabatrin therapy is efficacious at preventing CNS oxygen toxicity in swine, and a single dose is not acutely associated with retinotoxicity.

Decompression from Saturation Using Oxygen: Its Effect on DCS and RNA in Large Swine

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.

Cardiovascular parameters in a mixed-sex swine study of severe decompression sickness treated with the emulsified perfluorocarbon Oxycyte.

Intravenous perfluorocarbons (PFC) have reduced the effects of decompression sickness (DCS) and improved mortality rates in animal models. However, concerns for the physiological effects of DCS combined with PFC therapy have not been examined in a balanced mixed-sex population. Thirty-two (16 male, 16 female) instrumented and sedated juvenile Yorkshire swine were exposed to 200 feet of seawater (fsw) for 31 min of hyperbaric air. Pulmonary artery pressure (PAP), cardiac output (CO), and systemic arterial pressure (SAP) were monitored before (control) and after exposure. Animals were randomized to treatment with Oxycyte (5 ml/kg; Oxygen Biotherapeutics, Inc., Morrisville, NC) vs. saline (control) with 100% oxygen administered upon DCS onset; animals were observed for 90 min. Parameters recorded and analyzed included PAP, CO, and SAP. In all animals PAP began to rise prior to cutis marmorata (CM) onset, the first sign of clinical DCS, generally peaking after CM onset. Female swine, compared with castrated males, had a more rapid onset of CM (7.30 vs. 11.46 min postsurfacing) and earlier onset to maximal PAP (6.41 vs. 9.69 min post-CM onset). Oxycyte therapy was associated with a sustained PAP elevation above controls in both sexes (33.41 vs. 25.78 mmHg). Significant pattern differences in PAP, CO, and SAP were noted between sexes and between therapeutic groups. There were no statistically significant differences in survival or paralysis between the PFC and control groups during the 48-h observation period. In conclusion, Oxycyte therapy for DCS is associated with a prolonged PAP increase in swine. These species and sex differences warrant further exploration.