Hyperbaric Air Research Articles

Effects of hyperbaric oxygen therapy in the management of chronic wounds and its correlation with CD34(+) endothelial progenitor cells

To evaluate the effects of hyperbaric oxygen (HBO) therapy in the management of chronic wound and observe the correlation between wound healing and CD34+ endothelial progenitor cells (EPCs). A total of 119 patients with chronic wound in lower extremities lasting > 3 months were recruited for this randomized, single-center, placebo-controlled clinical trial. The changes of CD34+ average count before and after HBO therapy were detected by flow cytometry (FACS). There were 97 patients on long-term HBO therapy and in 22 patients on hyperbaric air therapy as control group. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell were determined respectively by FACs. The outcomes of two groups were compared. Treatment was administered within a single-place hyperbaric chamber for 90-min daily (session duration 120 min) for 5 days a week for 4 weeks (20 treatment sessions). The wound size decreased at the 4-week end point (62.7% ± 22.3% in the HBO group vs 34.4% ± 20.6% in the control group, P < 0.05). After 10 episodes of HBO therapies for chronic non-healing wound, the peripheral CD34+ EPCs average count rose from 0.24% ± 0.03% at pre-treatment to 1.32% ± 0.05% while the number was 1.75% ± 0.17% after 20 episodes of HBO (P < 0.05). Both were significantly different from that of the patients at pre-treatment. However the overall circulating white cell count was not significantly elevated. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell in HBO group were 5.8 and 5.2 folds than those at pre-treatment respectively. The number of EPCs was positively correlated with wound healing in lower extremities (correlation coefficient 0.84; P < 0.01). Adjunctive treatment of HBO facilitates the healing of chronic non-healing wound in selected patients through the mobilization of EPCs.

Effect of isobaric breathing gas shifts from air to heliox mixtures on resolution of air bubbles in lipid and aqueous tissues of recompressed rats

Deep tissue isobaric counterdiffusion that may cause unwanted bubble formation or transient bubble growth has been referred to in theoretical models and demonstrated by intravascular gas formation in animals, when changing inert breathing gas from nitrogen to helium after hyperbaric air breathing. We visually followed the in vivo resolution of extravascular air bubbles injected at 101 kPa into nitrogen supersaturated rat tissues: adipose, spinal white matter, skeletal muscle or tail tendon. Bubbles were observed during isobaric breathing-gas shifts from air to normoxic (80:20) heliox mixture while at 285 kPa or following immediate recompression to either 285 or 405 kPa, breathing 80:20 and 50:50 heliox mixtures. During the isobaric shifts, some bubbles in adipose tissue grew marginally for 10–30 min, subsequently they shrank and disappeared at a rate similar to or faster than during air breathing. No such bubble growth was observed in spinal white matter, skeletal muscle or tendon. In spinal white matter, an immediate breathing gas shift after the hyperbaric air exposure from air to both (80:20) and (50:50) heliox, coincident with recompression to either 285 or 405 kPa, caused consistent shrinkage of all air bubbles, until they disappeared from view. Deep tissue isobaric counterdiffusion may cause some air bubbles to grow transiently in adipose tissue. The effect is marginal and of no clinical consequence. Bubble disappearance rate is faster with heliox breathing mixtures as compared to air. We see no reason for reservations in the use of heliox breathing during treatment of air-diving-induced decompression sickness.

Hyperbaric oxygen therapy improves health‐related quality of life in patients with diabetes and chronic foot ulcer

Adjunctive treatment with hyperbaric oxygen therapy has recently been shown to improve ulcer healing in patients with chronic diabetic foot ulcer. The aim of the present study is to evaluate whether hyperbaric oxygen therapy improves the health related quality of life in these patients. Prospective randomized placebo-controlled double-blinded study setting using SF-36. A total of 75 patients were included in the study; 38 were randomized to hyperbaric oxygen therapy and 37 to placebo (hyperbaric air). The overall mean physical and mental summary scores for the entire study population at baseline were 29.6 ± 8.8 and 47.5 ± 12.4, respectively. There was a significant difference between baseline and 1 year follow-up responses to the mental summary score and two of the eight (SF-36) (?) domains in the -hyperbaric oxygen group, whereas no significant improvement of health related quality of life was seen in the placebo group. Comparing quality of life in patients who healed their ulcer (healers) with those who did not (non-healers), post-treatment levels of the mental health summary score, social functioning and role limitations due to physical and emotional health were significantly improved in healers. No differences were seen in any SF-36 (?) domain in non-healers. Hyperbaric oxygen therapy improves long-term health related quality of life in patients with chronic diabetic foot ulcers, possibly attributable to better ulcer healing.

Hyperbaric Air Therapy in Dogs for Clinical Veterinary Medicine: A Basic Study

Hyperbaric air therapy (HBA) is a treatment in which an animal is exposed to air pressurized to about 1.3 atmosphere absolute (ATA). Although HBA has already been administered to humans in medical applications, it has not been reported in clinical veterinary medicine. Therefore, we aimed to determine a safe protocol for dogs. To elucidate oxygen dynamics during HBA, we measured partial pressure of arterial oxygen, oxygen saturation of tissue, and partial pressure of transcutaneous oxygen in dogs. HBA could be performed safely with a protocol of pressurizing speed up to 0.1 ATA/min, maximum chamber pressure of up to 1.3 ATA, and pressure duration of around 45 min per treatment. Under these conditions, tissue was adequately oxygenated during and after treatment.

Hyperbaric Oxygen Therapy Facilitates Healing of Chronic Foot Ulcers in Patients With Diabetes

OBJECTIVEChronic diabetic foot ulcers are a source of major concern for both patients and health care systems. The aim of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) in the management of chronic diabetic foot ulcers.RESEARCH DESIGN AND METHODSThe Hyperbaric Oxygen Therapy in Diabetics with Chronic Foot Ulcers (HODFU) study was a randomized, single-center, double-blinded, placebo-controlled clinical trial. The outcomes for the group receiving HBOT were compared with those of the group receiving treatment with hyperbaric air. Treatments were given in a multi-place hyperbaric chamber for 85-min daily (session duration 95 min), five days a week for eight weeks (40 treatment sessions). The study was performed in an ambulatory setting.RESULTSNinety-four patients with Wagner grade 2, 3, or 4 ulcers, which had been present for >3 months, were studied. In the intention-to-treat analysis, complete healing of the index ulcer was achieved in 37 patients at 1-year of follow-up: 25/48 (52%) in the HBOT group and 12/42 (29%) in the placebo group (P = 0.03). In a sub-analysis of those patients completing >35 HBOT sessions, healing of the index ulcer occurred in 23/38 (61%) in the HBOT group and 10/37 (27%) in the placebo group (P = 0.009). The frequency of adverse events was low.CONCLUSIONSThe HODFU study showed that adjunctive treatment with HBOT facilitates healing of chronic foot ulcers in selected patients with diabetes.

Denitrogenation (Preoxygenation) as a Prophylactic Treatment for “Flier's Bends” During High Altitude Missions in Unpressurized Aircraft of the Allied Air Forces in World War II

Allied aviators flew missions in unpressurized planes to 20,000–30,000 feet and avoided hypoxia by using demand O2 equipment. With the advent of pressure demand O2 equipment, the pilot's ceiling was raised to 35,000–47,000 feet! Any mission flown above 20,000 feet increased their risk for decompression sickness (DCS); that is, gases dissolved in their tissues at sea level air pressure would come out of solution at hypobaric pressure to form bubbles (mostly N2) causing pain in the extremities and, in the worse cases, paralysis or death. DCS (aka “Caisson's disease/Diver's bends”) had long been recognized as a serious problem for men who decompressed too quickly from hyperbaric air pressure. “Flier's bends”, however, would not be appreciated until aeronautical engineering developed aircraft capable of flight above 20,000 feet, which finally occurred in the 1930s. Beginning in 1934, Harry Armstrong (Wright Field) would reveal that DCS occurred in men and animals during high altitude “chamber flights”. Armstrong showed in 1940 that 30 min of breathing pure O2 before ascending to altitude (preoxygenation) reduced both the level of N2 in the body (denitrogenation) and the risk of DCS. Breathing O2 for 30–40 min before flight or during ascent to 20,000 feet became standard operating procedure for high altitude missions in WWII. Today, astronauts use preoxygenation prior to extravehicular activity to reduce the risk of DCS.

Long-term treatment with hyperbaric air improves hyperlipidemia of db/db mice

Hyperbaric air (HBA) is used to improve healing of wounds including diabetic ulcer. The aim of this study was to clarify the effects of HBA exposure on lipid and glucose metabolism in db/db mice. HBA did not influence the weight of db/db mice. Serum levels of free fatty acid and triglyceride, but not glucose and insulin, were significantly decreased after 6 weeks of treatment with HBA. The mRNA expressions of CPT-1, PPARα and PGC-1α genes, which are related to lipid metabolism, were significantly up-regulated in the muscle and liver. Increases in TNFα and MCP1 mRNA, which impaired lipid metabolism, were also attenuated by HBA treatment. These results suggest that exposure of HBA could have beneficial effects on lipid metabolism in patients with type 2 diabetes mellitus.

Acclimation to decompression sickness in rats

Protection against decompression sickness (DCS) by acclimation to hyperbaric decompression has been hypothesized but never proven. We exposed rats to acclimation dives followed by a stressful "test" dive to determine whether acclimation occurred. Experiments were divided into two phases. Phase 1 rats were exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid decompression on one of the following regimens: 70 ft of seawater (fsw) for 9 days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days (S40), or unpressurized sham exposure for 9 days (Control). On the day following the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid decompression). Both L70 and S70 rats had significantly lower incidences of DCS than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the other regimens were lower than in Control rats but without statistical significance. Phase 2 used the most protective regimen from phase 1 (L70); rats were exposed to L70 or a similar regimen with a less stressful staged decompression. Another group was exposed to a single acclimation dive (70 fsw/30 min) on the day before the test dive. We observed a nonsignificant trend for the rapidly decompressed L70 dives to be more protective than staged decompression dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not provide protection. We conclude that protection against DCS can be attained with acclimating exposures that do not themselves cause DCS. The deeper acclimation dive regimens (70 fsw) provided the most protection.

Diabetic persons with foot ulcers and their perceptions of hyperbaric oxygen chamber therapy

To elucidate how diabetic patients with limb-threatening foot lesions perceive and evaluate content and organisation of treatment in a multi-place hyperbaric oxygen chamber. To our knowledge there are no patients' evaluations of diabetes care in a high-technology area like the hyperbaric oxygen chamber. The burden on persons with diabetic foot complications might be increased if adjuvant therapy with hyperbaric oxygen therapy (HBOT) within a locked airtight vessel is given. Explorative study. Participants were included in the HODFU study, a prospective randomised double-blind study, designed to evaluate whether HBOT heals more chronic foot ulcers than placebo treatment with hyperbaric air. Six females and 13 males, aged 44-83 years (median 70), with diabetic foot ulcers, participated. Focus-group interviews by an external evaluator. Management was perceived as well-functioning with competent staff delivering quick treatment in a positive manner and in good co-operation. HBOT sessions, in groups, were described as unproblematic and pleasant, through sharing experiences with others, although time-consuming and tiring. Recognising the responsible physician and communication with other physicians in the health-care chain was perceived as problematic. Placebo treatment, when given, did not reveal any problems; many perceived HBOT as the last resort and respondents had a negative view of future health and expressed fears of new wounds and amputation. From patients' perspective HBOT in the delivered health-care model was perceived as well-functioning, taking into consideration both technical and relational aspects of care in this high-technology environment. Communication with the patient and between different care givers, with a consistent message given and information about who is responsible and to whom one should turn, wherever treated, is the most crucial aspect of the model. Future fears need to be recognised and group interaction can be encouraged to share the burden of disease.

Arterial and pulmonary arterial hemodynamics and oxygen delivery/extraction in normal humans exposed to hyperbaric air and oxygen

Divers and hyperbaric chamber attendants breathe hyperbaric air routinely. Hyperbaric oxygen (HBO(2)) is used therapeutically frequently. Although much is understood about the hemodynamic physiology and gas exchange effects during hyperbaric air and HBO(2) exposure, arterial and pulmonary arterial (PA) catheter data, including blood gas values during hyperbaric air and HBO(2) exposure of normal humans, have not been reported. We exposed 10 healthy volunteers instrumented with arterial and PA catheters to air at 0.85, 3.0, 2.5, 2.0, 1.3 (decompression stop), 1.12 (decompression stop), and 0.85 atm abs (our altitude) and then at identical pressures breathing O(2) followed by atmospheric pressure air while we measured arterial and PA pressures (PAP), cardiac output (Q), and blood gas measurements from both arterial and PA catheters. Although hemodynamic changes occurred during exposure to both hyperbaric air and HBO(2), we observed a greater magnitude of change under HBO(2) conditions: heart rate changes ranged from -9 to -19% (air to O(2)), respiratory rate from -12 to -17%, Q from -7 to -18%, PAP from -18 to -19%, pulmonary vascular resistance from -38 to -48%, and right-to-left shunt fraction from -87 to -107%. Mixed venous CO(2) fell 8% from baseline during HBO(2) despite mixed venous O(2) tensions of several hundred Torr. The stroke volume, O(2) delivery, and O(2) consumption did not change across exposures. The arterial and mixed venous partial pressures of O(2) and contents were elevated, as predicted. O(2) extraction increased 37% during HBO(2).

The physiology and pathophysiology of the hyperbaric and diving environments

human exposure to the challenges of the underwater world has been traced back thousands of years (e.g., the diving women of Japan). However, the last century has seen an acceleration of activities with disparate foci on the “Silent World.” The variety and beauty of marine life attract growing

Microarray Analysis of Gene Expression in Rat Cortical Neurons Exposed to Hyperbaric Air and Oxygen

To gain a global view of the genomic response of neurons to normobaric and hyperbaric hyperoxic stress, we performed a microarray analysis of gene expression after exposure to varying levels of partial oxygen pressures. Rat neurons were exposed to normobaric hyperoxia, hyperbaric (2, 4, and 6 atmosphere absolute) air or hyperbaric O(2). We identified 183 genes significantly altered (increased or decreased >or=1.5-fold) in response to pressure and/or oxidative stress. Among them, 17 genes changed in response to all exposure conditions. More genes were altered in response to hyperbaric air than hyperbaric O(2). The altered genes included factors associated with stress responses, transport/neurotransmission, signal transduction, and transcription factors. The results may serve as guidance for selection of biomarkers of hyperoxia and hyperbaric O(2) response and provide a starting point for further studies to investigate the global molecular mechanisms underlying hyperbaric oxidative stress.

Comparison of the effects of 40% oxygen and two atmospheric absolute air pressure conditions on stress-induced premature senescence of normal human diploid fibroblasts

The pressure during hyperbaric oxygen treatment may increase oxygen toxicity via an augmented oxygen pressure in the gas. Nevertheless, only a few reports have been published on the effect of cells grown under 2 atmospheric absolute (ATA) pressure. To evaluate the effect of pressure on oxygen toxicity and to study effects in addition to oxygen toxicity, we designed an experiment to compare the effects of normobaric mild hyperoxia (NMH, 40% oxygen) and hyperbaric air condition (HA, air with 2 ATA) on human diploid fibroblasts (HDF) in a hyperbaric incubator. HDFs in both the NMH and the HA condition had a similar oxidative stress response and exhibited premature senescence. To investigate differences in gene profiling in cells grown in the NMH and HA conditions, samples from cells exposed to each condition were applied to microarrays. We found no expression difference in genes related to aging and deoxyribonucleic acid damage, but the expression of genes including cell adhesion, stress response, and transcription were significantly increased in fibroblasts that were responsive to pressure. Among 26 statistically reliable genes, the expression of apoptosis related genes such as ADAM22, Bax, BCL2L14, and UBD, as well as tumor suppressor-related genes like Axin2 and ATF, and also mitogen-activated protein kinase-related genes like mitogen-activated protein kinase kinase kinase 1, histamine receptor, and RAB24, were significantly changed in cells responsive to pressure-induced oxidative stress.

Repeated exposures to hyperbaric air suppress neurite outgrowth in PC12 cells

Objective: Scuba divers are at risk of central nervous system damage under hyperbaric exposure, which would directly causes lesions of neural cells.Method: After NGF stimulation, PC12 cells were compressed for 30 minutes as single exposure, and repeated exposures for 30 minutes were applied 3 times with intervals 3,15,30 minutes. Then neurite outgrowth was observed. Downstream signals of NGF (TrkA and ERK) were also examined under single and repeated exposures.Result: Repeated exposures to hyperbaric air with either 3 or 15 min interval suppresses NGF‐stimulated neurite outgrowth. Although TrkA showed no change in autophosphorylation, repeated exposures with 3 min interval reduced ERK protein expression significantly.Conclusion: Direct effect of repeated exposures to hyperbaric air on neural cells likely causes CNS lesions in scuba divers.

Repetitive hyperbaric oxygen exposures enhance sensitivity to convulsion by upregulation of eNOS and nNOS

Background: Repetitive hyperbaric oxygen (HBO) exposures as preconditioning methods produce ischemic tolerance, but may increase the risk of convulsions in patients. The purpose of this study was to investigate the mechanisms in increased sensitivity to convulsions and the role of nitric oxide (NO) and its synthases after repetitive HBO exposures. Methods: Mice were randomly assigned into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA) group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O 2, 6 ATA). The latency of convulsions was recorded. In addition, the levels of NO, NADPH-diaphorase, mRNA and protein expressions of NOS isoforms in hypothalamus and hippocampus were determined. Results: Latency to seizures was significantly shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in HBO group was increased. The number of NADPH-d positive cells and the levels of protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased. Conclusion: After repeated HBO exposures, elevated NO may enhance the sensitivity to convulsions and this may lead to seizures during the subsequent oxygen exposures. Prevention of seizures is needed when HBO is used as preconditioning method.

The effect of hyperbaric oxygen on regional brain and spinal cord levels of nitric oxide metabolites in rat

Hyperbaric oxygen (HBO 2) therapy is reported to be beneficial in transient brain ischemia. The present study was conducted to determine the influence of HBO 2 on metabolites of nitric oxide (NO) in brain and spinal cord of rats. Rats were exposed to room air (RA), normobaric air (NBA), normobaric oxygen (NBO 2), hyperbaric air (HBA) or HBO 2, the last two conditions at 2.5 ATA (atmosphere absolute) for 60 min. The results demonstrate that, compared to the NBA control, oxygen alone generally reduced tissue levels of NO x − (nitrite plus nitrate). On the other hand, 2.5 ATA alone tended to have a slight, if any, effect on tissue levels of NO x −. The combination of oxygen and pressure (i.e., HBO 2) generally led to an increase in tissue levels of NO x −. Based on these findings, it is concluded that HBO 2 appears to markedly increase NO function most notably in the corpus striatum, brainstem, cerebellum and spinal cord.

Decompression-Induced Ocular Tear Film Bubbles Reflect the Process of Denitrogenation

To confirm that the tear film bubbles observed after decompression from hyperbaric exposure are due to denitrogenation and to assess the time course of denitrogenation based on the number of ocular tear film bubbles. The study comprised two parts. In the first, subjects (n = 8) were compressed to a pressure of 2.0 ATA (atmospheres absolute; depth of 10 meters of sea water [msw]) for 60 minutes in a hyperbaric chamber on two separate occasions. On one occasion they breathed air, whereas on the second occasion they inspired pure oxygen. Before and within 30 minutes after each dive, the subjects' tear film was examined with a slit lamp microscope and the average number of bubbles recorded. Ultrasound reflectivity of the lens-vitreous humor compartments was also examined. In the second part of the study, subjects (n = 8) participated in two simulated dives in the hyperbaric chamber: 4.0 ATA (30 msw) for 15 minutes and 2.5 ATA (15 msw) for 180 minutes. The former was a no-stop decompression dive, whereas the latter required a 43-minute decompression stop at 3 msw. Ocular tear film examinations were conducted before the dive, as well as 30 minutes and 1 day, 2 days, and 3 days after the dives. The number of tear film bubbles increased significantly (P < 0.05) after the air dives to 2.0 ATA for 60 minutes, whereas there was no significant postdecompression increase in tear film when oxygen was inspired by the subjects during the dive. Posterior lens-vitreous humor reflectivity increased significantly after decompression from 2 ATA, when air was the breathing mixture, whereas no change in reflectivity was observed when oxygen was inspired during the dive. In the second part of the study, there was a significant elevation in tear film bubbles for 2 days after the two dives (P < 0.05). There was no significant difference in the number of ocular tear film bubbles between the two dives. After a hyperbaric air exposure, tear film bubbles reflect the process of denitrogenation, which may persist for up to 2 days after the decompression.

Prevention and suppression of pyrogenic fever in rabbits by hyperbaric oxygen

Current investigation was to determine whether hyperbaric oxygen had an effect on the febrile responses to systemic administration of lipopolysaccharide. An intravenous dose of lipopolysaccharide (2 μg/kg) caused an increase in core temperature accompanied by both plasma tumor necrosis factor-α and hypothalamic prostaglandin E 2 overproduction in rabbits. Administering hyperbaric oxygen (100% at 253 kPa) but not normobaric oxygen (100% at 101 kPa), once a day for consecutive 7 days prior to or 1 h after injecting lipopolysaccharide significantly reduced the lipopolysaccharide-induced elevation of both core temperature and circulating tumor necrosis factor-alpha. As compared to those of the simultaneous administration of normobaric air and lipopolysaccharide, administering hyperbaric oxygen or air plus lipopolysaccharide simultaneously had lesser febrile effects in terms of core temperature elevation, tumor necrosis factor-alpha overproduction and hypothalamic prostaglandin E 2 accumulation. However, the febrile responses produced by simultaneous application of normobaric oxygen plus lipopolysaccharide were not significantly different from those of normobaric air plus lipopolysaccharide. The results indicate that hyperbaric oxygen, and to some extent hyperbaric air, may cause prevention and suppression of pyrogenic fever by reducing overproduction of both circulating tumor necrosis factor-alpha and hypothalamic prostaglandin E 2.

Repeated Exposures to Hyperbaric Air Suppress Neurite Outgrowth in PC12 Cells

Hyperbaric exposure induces lesions of the CNS in scuba divers. Repeated exposures to hyperbaric air at 0.5 MPa for 30 min with short intervals suppressed NGF-stimulated neurite outgrowth, concomitant with a decrease in the protein expression of ERK in PC12 cells. Hyperbaric exposure most likely causes direct lesions of neural cells.

Hyperbaric Oxygen Preconditioning Induces Tolerance against Spinal Cord Ischemia by Upregulation of Antioxidant Enzymes in Rabbits

The present study examined the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen (HBO) preconditioning is triggered by an initial oxidative stress and is associated with an increase of antioxidant enzyme activities as one effector of the neuroprotection. New Zealand White rabbits were subjected to HBO preconditioning, hyperbaric air (HBA) preconditioning, or sham pretreatment once daily for five consecutive days before spinal cord ischemia. Activities of catalase (CAT) and superoxide dismutase were increased in spinal cord tissue in the HBO group 24 h after the last pretreatment and reached a higher level after spinal cord ischemia for 20 mins followed by reperfusion for 24 or 48 h, in comparison with those in control and HBA groups. The spinal cord ischemic tolerance induced by HBO preconditioning was attenuated when a CAT inhibitor, 3-amino-1,2,4-triazole,1 g/kg, was administered intraperitoneally 1 h before ischemia. In addition, administration of a free radical scavenger, dimethylthiourea, 500 mg/kg, intravenous, 1 h before each day's preconditioning, reversed the increase of the activities of both enzymes in spinal cord tissue. The results indicate that an initial oxidative stress, as a trigger to upregulate the antioxidant enzyme activities, plays an important role in the formation of the tolerance against spinal cord ischemia by HBO preconditioning.