Effects of high-intensity interval training with hyperbaric oxygen.

Hyperbaric Oxygen (HBO2) has been proposed as a pre-conditioning method to enhance exercise performance. Most prior studies testing this effect have been limited by inadequate methodologies. Its potential efficacy and mechanism of action remain unknown. We hypothesized that HBO2 could enhance aerobic capacity by inducing mitochondrial biogenesis via redox signaling in skeletal muscle. HBO2 was administered in combination with high-intensity interval training (HIIT), a potent redox stimulus known to induce mitochondrial biogenesis. Aerobic capacity was tested during acute hypobaric hypoxia seeking to shift the limiting site of whole body V̇O2 from convection to diffusion, more closely isolating any effect of improved oxidative capacity. Healthy volunteers were screened with sea-level (SL) V̇O2peak testing. Seventeen subjects were enrolled (10 men, 7 women, ages 26.5±1.3 years, BMI 24.6±0.6 kg m-2, V̇O2peak SL = 43.4±2.1). Each completed 6 HIIT sessions over 2 weeks randomized to breathing normobaric air, "HIIT+Air" (PiO2 = 0.21 ATM) or HBO2 (PiO2 = 1.4 ATM) during training, "HIIT+HBO2" group. Training workloads were individualized based on V̇O2peak SL test. Vastus Lateralis (VL) muscle biopsies were performed before and after HIIT in both groups. Baseline and post-training V̇O2peak tests were conducted in a hypobaric chamber at PiO2 = 0.12 ATM. HIIT significantly increased V̇O2peak in both groups: HIIT+HBO2 31.4±1.5 to 35.2±1.2 ml kg-1·min-1 and HIIT+Air 29.0±3.1 to 33.2±2.5 ml kg-1·min-1 (p = 0.005) without an additional effect of HBO2 (p = 0.9 for interaction of HIIT x HBO2). Subjects randomized to HIIT+HBO2 displayed higher skeletal muscle mRNA levels of PPARGC1A, a regulator of mitochondrial biogenesis, and HK2 and SLC2A4, regulators of glucose utilization and storage. All other tested markers of mitochondrial biogenesis showed no additional effect of HBO2 to HIIT. When combined with HIIT, short-term modest HBO2 (1.4 ATA) has does not increase whole-body V̇O2peak during acute hypobaric hypoxia. (ClinicalTrials.gov Identifier: NCT02356900; https://clinicaltrials.gov/ct2/show/NCT02356900).

International Multicenter Registry for Hyperbaric Oxygen Therapy: Results through June 2021.

Introduction: The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications. Methods: A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test. Results: Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss. Discussion: The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Hyperbaric Oxygen as Successful Monotherapy for a Severe Ulcerative Colitis Flare.

This report presents a case of severe ulcerative colitis treated with hyperbaric oxygen as successful monotherapy.

Renal Effects of Hyperbaric Oxygen Therapy in Patients with Diabetes Mellitus: A Retrospective Study.

Hyperbaric oxygen therapy (HBOT) is an adjunctive treatment for patients with diabetic foot ulcers. The prolonged high oxygen level used in HBOT can produce oxidative stress, which may be harmful to the kidney. Animal experiments suggest HBOT does not harm renal function and may have an antiproteinuric effect, but little is known on the effect of HBOT in humans. We performed a retrospective chart review of 94 patients with diabetes mellitus who underwent HBOT at our institution over an eight-year period. Thirty-two patients had serum creatinine levels within 60 days of the start and the end of treatment. Creatinine levels were 1.41 ± 0.89 mg/dl before and 1.52 ± 1.17 mg/dl after hyperbaric treatments with no statistically significant difference (mean (postcreatinine + precreatinine/2) = 0.10 mg/dl, SE = 0.11, t = 0.89). Twenty-three patients had proteinuria measurements before and after HBOT mainly by urine dipstick analysis. A Wilcoxon signed-rank test showed less proteinuria after HBOT than before (N = 23, p=0.002). Proteinuria was absent in 7 of 23 patients (30%) before HBOT and 13 of 23 patients (57%) after HBOT, a reduction by almost 50%. This observation is remarkable because oxidative stress might be expected to increase rather than decrease proteinuria.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

Hyperbaric oxygen therapy to prevent central airway stenosis after lung transplantation.

BACKGROUND: Central airway stenosis (CAS) is a severe airway complication after lung transplantation associated with bronchial ischemia and necrosis. We sought to determine whether hyperbaric oxygen therapy (HBOT), an established treatment for tissue ischemia, attenuates post-transplant bronchial injury. METHODS: We performed a randomized, controlled trial comparing usual care with HBOT (2 atm absolute for 2 hours × 20 sessions) in subjects with extensive airway necrosis 4 weeks after transplantation. Endobronchial biopsies were collected at 4, 7, and 10 weeks after transplantation for a quantitative polymerase chain reaction. Coprimary outcomes were incidence of airway stenting and acute cellular rejection (ACR) at 1 year. RESULTS: The trial was stopped after enrolling 20 subjects (n = 10 per group) after a pre-planned interim analysis showed no difference between usual care and HBOT groups in stenting (both 40%), ACR (70% and 40%, respectively), or CAS (40% and 60%, respectively). Time to first stent placement (median [interquartile range]) was significantly shorter in the HBOT group (150 [73-150] vs 186 [167-206] days, p < 0.05). HIF gene expression was significantly increased in donor tissues at 4, 7, and 10 weeks after transplantation but was not altered by HBOT. Subjects who developed CAS or required stenting had significantly higher HMOX1 and VEGFA expression at 4 weeks (both p < 0.05). Subjects who developed ACR had significant FLT1, TIE2, and KDR expression at 4 weeks (all p < 0.05). CONCLUSIONS: Incidence of CAS is high after severe, established airway necrosis after transplantation. HBOT does not reduce CAS severity or stenting. Elevated HMOX1 and VEGFA expressions appear to associate with airway complications.

Development of an International, Multicenter, Hyperbaric Oxygen Treatment Registry and Research Consortium: Protocol for Outcome Data Collection and Analysis.

BACKGROUND: Hyperbaric oxygen (HBO2)-oxygen at pressures higher than atmospheric-is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO2's main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO2 has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO2 therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO2 outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established. OBJECTIVE: The aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium. METHODS: A consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry. RESULTS: Early results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement. CONCLUSIONS: The registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18857.

Effects of sprint interval training on cardiorespiratory fitness while in a hyperbaric oxygen environment.

Objectives: Hyperbaric oxygen (HBO2) exposure may enhance cardiorespiratory fitness. Exercise training and HBO2 exposure stimulate mitochondrial biogenesis, increase capillary density, and induce adaptive antioxidant mechanisms. We hypothesized that an exercise regimen of sprint interval training (SIT) while breathing HBO2 would lead to a greater improvement in exercise performance compared to the same training breathing ambient air. Methods: Healthy long-term intermediate-altitude residents, ages 20-39 years, with normal spirometry and cardiorespiratory fitness were randomized to two groups: one performing six sessions of a SIT regimen over two weeks in a hyperbaric chamber (1.4 ATA [141.9 kPa], FiO2=1.0); the other performing under ambient pressure conditions (0.85 ATA [86.1 kPa], FiO2=0.21). Training effect was evaluated by comparing incremental cycle ergometry cardiopulmonary exercise testing before and after the training regimen. The primary outcome measure was peak oxygen consumption (V̇O2), while secondary outcomes included additional exercise parameters. The effect of study group on exercise parameters was assessed using two-factor repeated measures ANOVA. Results: Of 58 participants randomized, 49 completed the training program and all cardiopulmonary exercise tests (n=23 HBO2, n=26 ambient). Both groups experienced an increase in peak V̇O2: 8.1% HBO2 and 7.1% ambient; the differences were not significant (p=0.50). Secondary parameters of peak work rate and peak V̇E experienced a significantly higher change in the HBO2 group compared to the ambient group (p=0.05 and p=0.03, respectively). Conclusion: Cardiorespiratory fitness improved after a two-week SIT regimen, but improvement in peak V̇O2 was not significantly different between ambient and HBO2 groups.

Safety of hyperbaric oxygen therapy for management of central airway stenosis after lung transplant.

BACKGROUND: Central airway stenosis (CAS) is common after lung transplantation and causes significant post-transplant morbidity. It is often preceded by extensive airway necrosis, related to airway ischemia. Hyperbaric oxygen therapy (HBOT) is useful for ischemic grafts and may reduce the development of CAS. METHODS: The purpose of this study was to determine whether HBOT could be safely administered to lung transplant patients with extensive necrotic airway plaques. Secondarily, we assessed any effects of HBOT on the incidence and severity of CAS. Patients with extensive necrotic airway plaques within 1-2 months after lung transplantation were treated with HBOT along with standard care. These patients were compared with a contemporaneous reference group with similar plaques who did not receive HBOT. RESULTS: Ten patients received HBOT for 18.5 (interquartile range, IQR 11-20) sessions, starting at 40.5 (IQR 34-54) days after transplantation. HBOT was well tolerated. Incidence of CAS was similar between HBOT-treated patients and reference patients (70% vs 87%, respectively; P=.34), but fewer stents were required in HBOT patients (10% vs 56%, respectively; P=.03). CONCLUSIONS: This pilot study is the first to demonstrate HBOT safety in patients who develop necrotic airway plaques after lung transplantation. HBOT may reduce the need for airway stent placement in patients with CAS.

Spontaneous cerebral gas embolism and pulmonary arteriovenous malformation: a case report.

Pulmonary barotrauma can cause cerebral arterial gas embolism (CAGE) from pulmonary overdistension of alveoli forcing gas into the pulmonary vasculature. We report a case of CAGE in a man found to have occult pulmonary arteriovenous malformation (PAVM) and undiagnosed obstructive sleep apnea (OSA). A 46-year-old man was admitted to the hospital for an acute seizure and left-sided weakness, with telangiectasias on his lower lip and tongue. Brain-computed tomography (CT) showed gas emboli in the right hemisphere. Chest CT revealed a 1.8-cm PAVM in the posterior right costophrenic sulcus. A transthoracic echocardiogram showed no intracardiac shunt or patent foramen ovale. He was treated with phenytoin, lidocaine and hyperbaric oxygen. The PAVM was occluded with a detachable balloon followed by coil embolization. Polysomnography revealed severe obstructive sleep apnea, which was treated with CPAP. Seven years later, the patient was functioning at his pre-event baseline. We propose the CAGE was caused by high negative intrathoracic pressures while breathing against an obstructed upper airway, with air entrainment into the PAVM and subsequent arterialization.