Atm Absolute Research Articles

Hyperbaric oxygen therapy as an immunomodulatory intervention in COVID-19-induced ARDS: Exploring clinical outcomes and transcriptomic signatures in a randomised controlled trial

Immunomodulatory agents with the potential to reverse critical COVID-19, targeting host-virus immune response are needed.In this exploratory sub study of a randomised controlled clinical trial, critical COVID-19 patients with moderate acute respiratory distress syndrome at one Swedish university hospital were randomly assigned (1:1) to hyperbaric oxygen therapy (HBOT) group plus best practice, or best practice (Control). Follow-up was 30 days. HBOT was administered with five treatments at 2.4 atm absolute (ATA), lasting 80 min, within the first seven days. Clinical outcome, inflammatory markers, and bulk RNA sequencing (RNAseq) on peripheral blood mononuclear cells were analysed.Between December 3rd, 2020, and May 17th, 2021, 23 patients were randomised, and 17 were analysed. RNA-sequencing revealed 791 differentially expressed genes in the HBOT group compared to 46 in the control group at Day 7 vs. baseline. Gene set enrichment analysis revealed a unique transcriptomic signature associated with endoplasmic reticulum stress (ERS) in the HBOT group. Patients in the HBOT group recovered faster and had a shorter mean hospital length of stay (HLoS), 16 vs. 26 days (95.99 % CI -16-0), p = 0.045. National early warning score (NEWS) was lower in the HBOT group (ANOVA, F [8, 120] = 3.817, p < 0.001) and PaO2/FiO2 was higher in the HBOT group (Mixed effects model, F [8, 94] = 2.900, p < 0.01).We showed a unique transcriptomic signature related to viral-induced ERS in critically ill COVID-19 patients treated with HBOT. The finding was associated with a positive clinical outcome; the HBOT patients recovered faster and had a reduced HLoS compared with controls. Trial registrationNCT04327505 (March 31, 2020) and EudraCT 2020-001349-37 (April 24, 2020).

Effects of mild hyperbaric oxygen therapy on timing sequence recovery of muscle fatigue in chinese university male athletes

ObjectivesThis study aimed to investigate the timing sequence recovery effects of single and repeated Mild Hyperbaric Oxygen Therapy (MHOT) on muscle fatigue induced by cycling exercise through a comprehensive set of parameters. MethodsThis study employed a controlled crossover design involving 12 Chinese secondary national-level male athletes. Each participant completed two identical trials over six days. Each trial consisted of a 90-min cycling exercise followed by either a Control (CON) intervention (1 atm absolute (ATA), 20.9 % oxygen, 60 min) or MHOT intervention (1.25 ATA, 26%–28 % oxygen, 60 min). Various physiological parameters including Rating of Perceived Exertion (RPE), Heart Rate (HR), Peripheral Oxygen Saturation (SpO2), Perfusion Index (PI%), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Lactic Acid (LA), Blood Urea Nitrogen (BUN), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Standing Long Jump Distance (SLJ) were measured at six different time points throughout the trials. ResultsRPE revealed that the MHOT group experienced reduced subjective fatigue in comparison to the CON group (P < 0.05). Additionally, MHOT demonstrated quicker recovery in HR and PI% compared to the CON group (P < 0.05). Regarding CK, LA, BUN, SOD, and MDA levels, the MHOT group exhibited accelerated recovery post-6 intervention and at the 24-h mark after six interventions, showing significant improvement over the CON group (P < 0.05). However, no notable disparity was observed between groups concerning SpO2, LDH, and SLJ. ConclusionsBoth single and repeated sessions of MHOT demonstrated efficacy in alleviating subjective fatigue and promoting recovery of heart rate and blood perfusion following muscle fatigue, ensuring parallel structure and consistency in their effects. Repeated MHOT sessions (six times) exhibit a significant reduction in levels of blood markers associated with muscle damage, metabolites, and oxidative stress. However, the impact of a single MHOT intervention was less pronounced.

Prognostic factors of hyperbaric oxygen therapy for patients with delayed encephalopathy after acute carbon monoxide poisoning

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a disease with an incomplete pathological mechanism, long treatment time, and uncertain factors affecting the therapeutic effect. This study explored prognostic factors for DEACMP patients treated with hyperbaric oxygen therapy (HBOT) in 15 hospitals in China. The findings might provide a theoretical basis for further improving the prognosis of DEACMP patients.In this study, data from 330 patients with DEACMP who were admitted to HBOT centers of 15 hospitals in Hunan Province (China) from June 2015 to June 2020 were retrospectively analyzed, and their medical records related to disease prognosis were collected and followed up by telephone. Univariate and multivariate analyses were used to identify independent risk factors for the prognosis of DEACMP patients after HBOT. Univariate analysis revealed 11 possible prognostic factors. Consistent with univariate analysis, multivariate analysis found that underlying diseases (Odds radio(OR) = 2.886, P = 0.048), hypermyotonia (OR = 5.2558, P = 0.008), and HBOT pressure no less Than 2.3 atm absolute (ATA) ((OR = 7.812, P = 0.004) were identified as independent prognostic factors among 20 variables for poor prognosis of DEACMP patients treated with HBOT in the study. This multicenter retrospective analysis revealed that the adverse prognostic markers for DEACMP patients treated with HBOT might be underlying diseases, hypermyotonia, and an HBOT pressure of 2.3 ATA or higher.

Safety evaluation of carbon tetrafluoride as an inert hyperbaric breathing gas in Sprague-Dawley rats

Carbon tetrafluoride (CF4) is an inert gas with higher molecular weight and lower water solubility than commonly used hyperbaric breathing gases. These inert gas properties decrease time required to decompress and avoid decompression sickness after deep dives. To assess CF4 toxicity, Sprague-Dawley rats were exposed to 8 atm absolute (ATA) air (10 males, 10 females) or 8 ATA 79% CF4/21% O2 (25 males, 25 females). Exposures were 30 min daily for 5 days. Rat behavior was normal throughout the testing period. There were no gross or microscopic pathology abnormalities following repeat dose exposure. Male body weight trends were similar between groups. Female body weight trends were 0.5 ± 0.8% day−1 for hyperbaric air exposure and − 0.2 ± 0.8% day−1 for hyperbaric CF4 exposure (P = 0.01) but remained within literature cited norms. Organ weights and hematologic indices remained within or near literature normal ranges. Clinical chemistry panels showed no signs of toxicity in renal or hepatic biomarkers. Polychromatic erythrocyte micronucleus frequency showed no chromosomal damage. Comet assay showed no DNA damage in lung tissue. Females exposed to CF4 had 2.5 times greater percent tail DNA in liver tissue than controls (P = 0.009). However this result remained within the normal range of local negative controls. A bacterial reverse mutation assay with exposure to 1 ATA 79% CF4/21% O2 for 72 h was nonmutagenic in four strains of Salmonella typhimurium and one strain of Escherichia coli. Overall, there was no evidence that CF4 caused organ toxicity or genetic toxicity.

Hypothalamic impairment underlying heat intolerance in pregnant mice

Pregnant women are vulnerable to heat stroke reactions caused by high environmental temperatures. Heat intolerance is associated with hypothalamic impairment. Here, we aim to ascertain whether pregnancy causes heat intolerance by inducing hypothalamic impairment in mice. In the heated groups, mice were exposed to whole body heating (WBH; 41.2 °C for 1 h) in an environment-controlled chamber. Then, they were returned to normal room temperature (26 °C) immediately after WBH. In the hyperbaric oxygen therapy (HBO2T) groups, mice were exposed to 100% O2 at 2.0 atm absolute (ATA) for 4 h immediately post-WBH. Mice that survived after 4 h of WBH were considered survivors. Here, we show that when pregnant mice underwent non-HBO2T (21% O2 at 1.0 ATA for 4 h) after WBH, the survival rate was 4/20, and the core temperature at 4 h post-WBH was 31.2 ± 0.2 °C. Both the survival rate and core temperature of HBO2T pregnant mice (10/10 and 35.2 ± 0.3 °C, respectively) were significantly greater than those in non-HBO2T pregnant mice. Compared to non-HBO2T heated mice, the HBO2T heated mice exhibited lower neurological severity scores, reduced hypothalamic neuronal damage, fewer apoptotic cells, reduced multiorgan damage scores, and lower hypothalamic levels of proinflammatory cytokines and nitrogen and oxygen radical species. Compared to non-HBO2T heated mice, the HBO2T-treated heated mice had significantly higher hypothalamic-pituitary-adrenal axis activity (evidenced by higher serum levels of both adrenocorticotrophic hormone and corticosterone). In conclusion, pregnancy induces heat intolerance by inducing hypothalamic impairment in mice. Additionally, HBO2T protects against heat intolerance in pregnant mice by preserving hypothalamic integrity.

MRI of cerebral blood flow under hyperbaric conditions in rats.

Hyperbaric oxygen (HBO) therapy has a number of clinical applications. However, the effects of acute HBO on basal cerebral blood flow (CBF) and neurovascular coupling are not well understood. This study explored the use of arterial spin labeling MRI to evaluate changes in baseline and forepaw stimulus-evoked CBF responses in rats (n = 8) during normobaric air (NB), normobaric oxygen (NBO) (100% O2 ), 3 atm absolute (ATA) hyperbaric air (HB) and 3 ATA HBO conditions. T1 was also measured, and the effects of changes in T1 caused by increasing oxygen on the CBF calculation were investigated. The major findings were as follows: (i) increased inhaled oxygen concentrations led to a reduced respiration rate; (ii) increased dissolved paramagnetic oxygen had significant effects on blood and tissue T1 , which affected the CBF calculation using the arterial spin labeling method; (iii) the differences in blood T1 had a larger effect than the differences in tissue T1 on CBF calculation; (iv) if oxygen-induced changes in blood and tissue T1 were not taken into account, CBF was underestimated by 33% at 3 ATA HBO, 10% at NBO and <5% at HB; (v) with correction, CBF values under HBO, HB and NBO were similar (p > 0.05) and all were higher than CBF under NB by ~40% (p < 0.05), indicating that hypercapnia from the reduced respiration rate masks oxygen-induced vasoconstriction, although blood gas was not measured; and (vi) substantial stimulus-evoked CBF increases were detected under HBO, similar to NB, supporting the notion that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism. CBF MRI provides valuable insights into the effects of oxygen on basal CBF and neurovascular coupling under hyperbaric conditions. Copyright © 2016 John Wiley & Sons, Ltd.

Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages.

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.

Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain

Earlier research has demonstrated that hyperbaric oxygen (HBO2) can produce an antinociceptive effect in models of acute pain. Recent studies have revealed that HBO2 can produce pain relief in animal models of chronic pain as well. The purpose of the present investigation was to ascertain whether HBO2 treatment might suppress allodynia in rats with neuropathic pain and whether this effect might be blocked by the opioid antagonist naltrexone (NTX). Male Sprague Dawley rats were subjected to a sciatic nerve crush under anesthesia and mechanical thresholds were assessed using an electronic von Frey anesthesiometer. The time course of the HBO2-induced anti-allodynic effect in different treatment groups was plotted, and the area-under-the-curve (AUC) was determined for each group. Seven days after the nerve crush procedure, rats were treated with HBO2 at 3.5atm absolute (ATA) for 60min and exhibited an anti-allodynic effect, compared to nerve crush-only control rats. Twenty-four hours before HBO2 treatment, another group of rats was implanted with Alzet® osmotic minipumps that continuously released NTX into the lateral cerebral ventricle for 7 days. These NTX-infused, HBO2-treated rats exhibited an allodynic response comparable to that exhibited by rats receiving nerve crush only. Analysis of the AUC data showed that HBO2 significantly reduced the nerve crush-induced allodynia; this anti-allodynic effect of HBO2 was reversed by NTX. These results implicate opioid receptors in the pain relief induced by HBO2.

Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats

BackgroundHemorrhagic transformation (HT) can be a devastating complication of ischemic stroke. Hyperbaric oxygen preconditioning (HBO-PC) has been shown to improve blood-brain barrier (BBB) permeability in stroke models. The purpose of this study is to examine whether HBO-PC attenuates HT after focal cerebral ischemia, and to investigate whether the mechanism of HBO-PC against HT includes up-regulation of antioxidants in hyperglycemic rats.MethodsMale Sprague-Dawley rats (280-320 g) were divided into the following groups: sham, middle cerebral artery occlusion (MCAO) for 2 h, and MCAO treated with HBO-PC. HBO-PC was conducted giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at every 24 h interval for 5 days. At 24 h after the last session of HBO-PC, rats received an injection of 50% glucose (6 ml/kg intraperitoneally) and were subjected to MCAO 15 min later. At 24 h after MCAO, neurological behavior tests, infarct volume, blood-brain barrier permeability, and hemoglobin content were measured to evaluate the effect of HBO-PC. Western blot analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was evaluated at multiple time-points before and after MCAO.ResultsHBO-PC improved neurological behavior test, and reduced infarction volume, HT and Evans blue extravasation in the ipsilateral hemisphere at 24 h after MCAO. Western blot analysis failed to demonstrate up-regulation of Nrf2 in HBO-PC group before and after MCAO. Paradoxically, HBO-PC decreased HO-1 expression at 24 h after MCAO, as compared with htMCAO group.ConclusionsHBO-PC improved neurological deficits, infarction volume, BBB disruption, and HT after focal cerebral ischemia. However, its mechanism against focal cerebral ischemia and HT may not include activation of Nrf2 and subsequent HO-1 expression.

Effects of hyperoxia on ventilation and pulmonary hemodynamics during immersed prone exercise at 4.7 ATA: possible implications for immersion pulmonary edema

Immersion pulmonary edema (IPE) can occur in otherwise healthy swimmers and divers, likely because of stress failure of pulmonary capillaries secondary to increased pulmonary vascular pressures. Prior studies have revealed progressive increase in ventilation [minute ventilation (Ve)] during prolonged immersed exercise. We hypothesized that this increase occurs because of development of metabolic acidosis with concomitant rise in mean pulmonary artery pressure (MPAP) and that hyperoxia attenuates this increase. Ten subjects were studied at rest and during 16 min of exercise submersed at 1 atm absolute (ATA) breathing air and at 4.7 ATA in normoxia and hyperoxia [inspired P(O(2)) (Pi(O(2))) 1.75 ATA]. Ve increased from early (E, 6th minute) to late (L, 16th minute) exercise at 1 ATA (64.1 +/- 8.6 to 71.7 +/- 10.9 l/min BTPS; P < 0.001), with no change in arterial pH or Pco(2). MPAP decreased from E to L at 1 ATA (26.7 +/- 5.8 to 22.7 +/- 5.2 mmHg; P = 0.003). Ve and MPAP did not change from E to L at 4.7 ATA. Hyperoxia reduced Ve (62.6 +/- 10.5 to 53.1 +/- 6.1 l/min BTPS; P < 0.0001) and MPAP (29.7 +/- 7.4 to 25.1 +/- 5.7 mmHg, P = 0.002). Variability in MPAP among subjects was wide (range 14.1-42.1 mmHg during surface and depth exercise). Alveolar-arterial Po(2) difference increased from E to L in normoxia, consistent with increased lung water. We conclude that increased Ve at 1 ATA is not due to acidosis and is more consistent with respiratory muscle fatigue and that progressive pulmonary vascular hypertension does not occur during prolonged immersed exercise. Wide variation in MPAP among healthy subjects is consistent with variable individual susceptibility to IPE.

Short oxygen prebreathe periods reduce or prevent severe decompression sickness in a 70-kg swine saturation model

Disabled submarine (DISSUB) survivors are expected to achieve saturation with inert gas. However, rescue procedures may not accommodate staged decompression, raising the potential for severe decompression sickness (DCS). Alternatives to standard recompression therapy are needed. It has been demonstrated in humans that isobaric oxygen "prebreathing" (OPB) can accelerate decompression in a DISSUB scenario. In-70 kg swine saturated at 2.82 atm absolute (ATA), 1 h of OPB eliminated death and reduced severe DCS. We hypothesized that even shorter periods (<1 h) of OPB before no-stop decompression from saturation at 2.82 ATA could reduce the incidence of DCS in a large animal model. Catheterized Yorkshire swine (68.8 +/- 1.7 kg) in individual Plexiglas boxes within a large animal hyperbaric chamber were compressed to 2.82 ATA for 22 h. Following saturation and while still at depth, breathing gas was switched to >95% O(2) for 45 min (OPB(45)), 15 min (OPB(15)), or 5 min (OPB(05)) of OPB, or no OPB (control). The chamber was then decompressed without stops (0.91 ATA/min). Observers then entered the chamber and recorded signs of DCS for 2 h. All OPB periods significantly reduced the risk of developing type II DCS. OPB(45) eliminated severe DCS. Controls had a 2.5 times greater risk of developing type II DCS than OPB(05) (P = 0.016). OPB(45) and OPB(15) significantly reduced type I DCS compared with controls. These results support the potential of OPB as an alternative to staged decompression and that OPB could be expected to improve outcome in a DISSUB rescue scenario.

Phosphodiesterase-5 inhibitors oppose hyperoxic vasoconstriction and accelerate seizure development in rats exposed to hyperbaric oxygen

Oxygen is a potent cerebral vasoconstrictor, but excessive exposure to hyperbaric oxygen (HBO(2)) can reverse this vasoconstriction by stimulating brain nitric oxide (NO) production, which increases cerebral blood flow (CBF)-a predictor of O(2) convulsions. We tested the hypothesis that phosphodiesterase (PDE)-5 blockers, specifically sildenafil and tadalafil, increase CBF in HBO(2) and accelerate seizure development. To estimate changes in cerebrovascular responses to hyperoxia, CBF was measured by hydrogen clearance in anesthetized rats, either control animals or those pretreated with one of these blockers, with the NO inhibitor N(omega)-nitro-l-arginine methyl ester (l-NAME), with the NO donor S-nitroso-N-acetylpenicillamine (SNAP), or with a blocker combined with l-NAME. Animals were exposed to 30% O(2) at 1 atm absolute (ATA) ("air") or to 100% O(2) at 4 or 6 ATA. EEG spikes indicated central nervous system CNS O(2) toxicity. The effects of PDE-5 blockade varied as a positive function of ambient Po(2). In air, CBF did not increase significantly, except after pretreatment with SNAP. However, at 6 ATA O(2), mean values for CBF increased and values for seizure latency decreased, both significantly; pretreatment with l-NAME abolished these effects. Conscious rats treated with sildenafil before HBO(2) were also more susceptible to CNS O(2) toxicity, as demonstrated by significantly shortened convulsive latency. Decreases in regional CBF reflect net vasoconstriction in the brain regions studied, since mean arterial pressures remained constant or increased throughout. Thus PDE-5 blockers oppose the protective vasoconstriction that is the initial response to hyperbaric hyperoxia, decreasing the safety of HBO(2) by hastening onset of CNS O(2) toxicity.

Hyperbaric oxygen preconditioning reduces ischemia–reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain

This study examined the hypothesis that apoptotic inhibition via mitochondrial pathway was involved in hyperbaric oxygen preconditioning (HBO-PC)–induced neuroprotection on ischemia–reperfusion injury in rat brain. Male Sprague–Dawley rats (250∼280 g, n=144) were divided into control, middle cerebral artery occlusion (MCAO) for 90 min, and HBO-PC plus MCAO groups. HBO-PC was conducted four times by giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at 12 h intervals for 2 days. At 24 h after the last HBO-PC, MCAO was performed and at 24 h after MCAO, neurological function, brain water content, infarct volume, and cell death were evaluated. Enzymatic activity of capase-3 and −9, and expression of cytochrome c, Bcl-2 and Bax proteins were performed in the samples from hippocampus, ischemic penumbra and core of the brain cortex, respectively. HBO-PC reduced brain edema, decreased infarction volume, and improved neurological recovery. HBO-PC reduced cytoplasm cytochrome c levels, decreased caspase enzyme activity, upregulated the ratio of Bcl-2 and Bax expression, and abated the apoptosis of ischemic tissue. HBO-PC protects brain tissues from ischemia–reperfusion injury by suppressing mitochondrial apoptotic pathways.

Review of Equine Hyperbaric Medicine

Hyperbaric oxygen therapy appears to be a promising adjunctive treatment for a variety of equine disorders, including laminitis and other ischemic injuries. Hyperbaric oxygen (HBO) is a high-dose oxygen inhalation therapy that is achieved by having the patient breathe 100% oxygen inside a pressurized hyperbaric chamber. The delivery of oxygen to the tissues is through respiration because there is insufficient absorption of oxygen through the skin. The benefits of HBO are derived from both the physiologic and pharmacologic effects of high-dose oxygen. HBO is based on two physical factors related to the hyperbaric environment: mechanical effects of pressure and increased oxygenation of tissues. The use of HBO by veterinary medical hospitals is in its infancy. Our clinic has currently treated more than 250 patients in our HBO chamber. Patients included pregnant animals as well as neonatal foals, with no adverse effects noted. Patients have been pressurized from 1.5 to 3 ATA (ATM absolute) ranging from 60 to 90 minutes at treatment pressure (depth). Hagyard Equine Medical Institute has used HBO as adjunctive therapy for fungal disease (fungal pneumonia); thermal burns, carbon monoxide, smoke inhalation; closed head injuries; ileus; central nervous system edema/perinatal asphyxia; peripheral neuropathies; sports injuries (exertional rhabdomyolysis); cellulitis; compartment syndrome; and ischemic injuries (laminitis ). In carefully selected patients, the addition of HBO therapy to standard measures may improve clinical outcomes. Further research is needed in the field of equine HBO medicine.

Effects of head and body cooling on hemodynamics during immersed prone exercise at 1 ATA

Immersion pulmonary edema (IPE) is a condition with sudden onset in divers and swimmers suspected to be due to pulmonary arterial or venous hypertension induced by exercise in cold water, although it does occur even with adequate thermal protection. We tested the hypothesis that cold head immersion could facilitate IPE via a reflex rise in pulmonary vascular pressure due solely to cooling of the head. Ten volunteers were instrumented with ECG and radial and pulmonary artery catheters and studied at 1 atm absolute (ATA) during dry and immersed rest and exercise in thermoneutral (29-31 degrees C) and cold (18-20 degrees C) water. A head tent varied the temperature of the water surrounding the head independently of the trunk and limbs. Heart rate, Fick cardiac output (CO), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and central venous pressure (CVP) were measured. MPAP, PAWP, and CO were significantly higher in cold pool water (P < or = 0.004). Resting MPAP and PAWP values (means +/- SD) were 20 +/- 2.9/13 +/- 3.9 (cold body/cold head), 21 +/- 3.1/14 +/- 5.2 (cold/warm), 14 +/- 1.5/10 +/- 2.2 (warm/warm), and 15 +/- 1.6/10 +/- 2.6 mmHg (warm/cold). Exercise values were higher; cold body immersion augmented the rise in MPAP during exercise. MAP increased during immersion, especially in cold water (P < 0.0001). Except for a transient additive effect on MAP and MPAP during rapid head cooling, cold water on the head had no effect on vascular pressures. The results support a hemodynamic cause for IPE mediated in part by cooling of the trunk and extremities. This does not support the use of increased head insulation to prevent IPE.

Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure

Accumulating evidence suggests that hyperbaric oxygen (HBO) stimulates neuronal nitric oxide (NO) synthase (NOS) activity, but the influence on endothelial NOS (eNOS) activity and vascular NO bioavailability remains unclear. We used a bioassay employing rat aortic rings to evaluate vascular NO bioavailability. HBO exposure to 2.8 atm absolute (ATA) in vitro decreased ACh relaxation. This effect remained unchanged, despite treatment with SOD-polyethylene glycol and catalase-polyethylene glycol, suggesting that the reduction in endothelium-derived NO bioavailability was independent of superoxide production. In vitro HBO induced contraction of resting aortic rings with and without endothelium, and these contractions were reduced by the NOS inhibitor N(omega)-nitro-l-arginine. In addition, in vitro HBO attenuated the vascular contraction produced by norepinephrine, and this effect was reversed by N(omega)-nitro-l-arginine, but not by endothelial denudation. These findings indicate stimulation of extraendothelial NO production during HBO exposure. A radiochemical assay was used to assess NOS activity in rat aortic endothelial cells. Catalytic activity of eNOS in cell homogenates was not decreased by HBO, and in vivo HBO exposure to 2.8 ATA was without effect on eNOS activity and/or vascular NO bioavailability in vitro. We conclude that HBO reduces endothelium-derived NO bioavailability independent of superoxide production, and this effect seems to be unrelated to a decrease in eNOS catalytic activity. In addition, HBO increases the resting tone of rat aortic rings and attenuates the contractile response to norepinephrine by endothelium-independent mechanisms that involve extraendothelial NO production.

Brown recluse spider envenomation: a prospective trial of hyperbaric oxygen therapy.

Loxosceles reclusa (brown recluse) spider bites can produce severe skin lesions that may necessitate extensive surgical repair. This study delineated the effects of hyperbaric oxygen (HBO) therapy on these lesions by performing a prospective controlled animal study. After approval by the Institutional Animal Care and Use Committee, 41 New Zealand white rabbits received 64 intradermal injections of 73 microL of raw venom extract mixed with physiologic buffered saline (Dulbecco's solution). Control injections were made with buffer. The animals were divided into 5 groups: 1) venom and no HBO; 2) venom and 1 immediate HBO treatment (100% O2); 3) venom and immediate HBO with 10 treatments (100% O2); 4) venom and then delayed (48 hr) HBO therapy with 10 treatments (100% O2); and 5) venom and immediate hyperbaric treatment with normal inspired PO2 for 10 treatments (8.4% O2). Three animals in group 2 also received a control sodium citrate buffer injection. HBO treatments were at 2.5 atm absolute (ATA) for 90 minutes twice daily. Daily measurements were made of the lesion diameter, and skin blood flow using a laser Doppler probe. There was no significant effect of HBO on blood flow at the wound center or 1-2 cm from the wound center. Standard HBO significantly decreased wound diameter at 10 days (p < 0.0001; ANOVA), whereas hyperbaric treatment with normoxic gas had no effect. Histologic preparations from 2 animals in each group revealed that there were more polymorphonuclear leukocytes in the dermis of all the HBO-treated animals when compared with the venom-alone and sodium-citrate controls. HBO treatment within 48 hours of a simulated bite from L. reclusa reduces skin necrosis and results in a significantly smaller wound in this model. The mechanism appears unrelated to augmented local blood flow between treatments.

Recovery from hyperoxic depression of pulmonary 5-hydroxytryptamine clearance: effect of inspired O2 tension.

The present study evaluated the effect of inspired O2 tension\((PI_{O_2 } )\) on the extent and rapidity of recovery from hyperoxic depression of pulmonary 5-hydroxytryptamine (5-HT) clearance. Rats were exposed to either 100% O2 at 4 atm absolute (ATA) or 6% O2 at 4 ATA (controls) for 60 min and then transferred to chambers containing either compressed air at 3.5 ATA or compressed air, 30% O2 or 70% O2 at 1 ATA for recovery. 5-HT clearance by the isolated, perfused lung was measured after 1, 4 or 24 h recovery. Clearances by the lungs of nonexposed rats and control rats were indistinguishable. In contrast, 5-HT clearances by the lungs of rats exposed to 100% O2 at 4 ATA (hyperbaric O2; HBO) were markedly depressed 1 h after exposure (P < 0.001 vs. controls). In HBO-exposed rats breathing compressed air or 30% O2 at 1 ATA during the recovery period, depressed 5-HT clearances seen 1 h after exposure returned to control levels 4 h following exposure. In HBO-exposed rats breathing 70% O2 at 1 ATA or compressed air at 3.5 ATA during recovery, 5-HT clearance remained significantly depressed (P < 0.02) 24 h after exposure. These results (1) confirm that depression of pulmonary 5-HT clearance is a reversible alteration of lung function in the rat due to high partial pressures of inspired O2, (2) indicate that the extent and rate of reversibility is dependent upon postexposure\(PI_{O_2 } \), and (3) suggest that repair of hyperoxic lung damage may occur rapidly and completely while the animal is breathing an elevated, nontoxic O2 tension (i.e., 30% O2 at 1 ATA).

Calibration of condenser microphones under increased atmospheric pressures.

The sensitivity and frequency response characteristics of type-L standard laboratory microphones were measured with an electrostatic actuator at surface and at 12 different levels to 31 atm absolute (ATA) in a hyperbaric chamber. The microphones were measured in compressed air and a helium-air environment, with and without the capillary pin. In addition, one microphone remained at a depth of 31 ATA for 24 h to measure its stability under pressure. Results indicated a loss in sensitivity in compressed air and helium-air as a function of pressure. In a compressed-air environment a resonant peak occurred at 4000 Hz, which shifted to 8000 Hz in the helium-air environment. The microphones showed extremely close agreement between compression and decompression, between different pressurizations, and between different microphones. Also, there was no change in sensitivity over a 24-h period of pressurization at 31 ATA. Calibration data at several pressures are given.