Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that four daily 60-min HBO2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the four HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain.
Hyperbaric oxygen treatment of mice can induce a two-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems.
Hyperbaric oxygen; antinociception; nitric oxide; opioid receptors; mice
Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.
C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O2, 3.0 ATA, 1–2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-α, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4+ and CD8+ T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB) dysfunction and hypothermia.
The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.
Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.
Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2′-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis.
α-Lipoic acid (LA) has been found previously to accelerate wound repair in patients affected by chronic wounds who underwent hyperbaric oxygen (HBO) therapy. Because proteinases are important in wound repair, we hypothesized that LA may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Patients undergoing HBO therapy were double-blind randomized into two groups: the LA group and the placebo group. Gene expression profiles for MMPs and for angiogenesis mediators were evaluated in biopsies collected at the first HBO session, at the seventh HBO session, and after 14 days of HBO treatment. ELISA tests were used to validate microarray expression of selected genes. LA supplementation in combination with HBO therapy downregulated the inflammatory cytokines and the growth factors which, in turn, affect MMPs expression. The disruption of the positive autocrine feedback loops that maintain the chronic wound state promotes progression of the healing process.
Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO2) may be an effective option for some patients.
In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded.
Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO2 were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO2 is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies.
Based on the evidence and expert consensus opinion,
HBO2 is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO2 therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO2 may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft-tissue necrosis, and osteonecrosis); andHBO2 may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis.
Hyperbaric oxygen therapy; HBO2; late radiation tissue injury; lrti; radiotherapy; gynecologic cancers; adverse effects; cancer pain; clinical practice guideline; systematic review
A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone-marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, α-smooth-muscle actin, and von-Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction-shortening, LV wall-thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy.
Mesenchymal stem cell; hyperbaric oxygen; myocardial infarction; stem-cell therapy
Hemorrhagic 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.
Male 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.
HBO-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.
HBO-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.
Hemorrhagic transformation; MCAO; Hyperbaric oxygen preconditioning; Nuclear factor erythroid 2-related factor 2 (Nrf2); Heme oxygenase-1 (HO-1)
Hemorrhagic cystitis consists of acute or insidious diffuse bleeding from the bladder mucosa. It can be caused by radiation, drugs, autoimmune diseases, viral and bacterial infections, etc. Hemorrhagic cystitis is a well-recognized complication of cyclophosphamide therapy and it can be potentially fatal. We discuss two cases of cyclophosphamide-induced hemorrhagic cystitis where outcome of conventional management was not satisfactory and a novel therapy using hyperbaric oxygen was used. Hyperbaric oxygen therapy (HBOT) reduces inflammation, stimulates neoangiogenesis, maintains tissue oxygenation and heals tissue hypoxia and radio necrosis. Patients received 100% oxygen in a hyperbaric chamber at 2.5 atmosphere absolute (ATA) for 90 minutes, 5 days a week. One patient was given 36 sessions and the other was given 19 sessions of HBOT. HBOT resulted in complete cessation of bleeding; no side effect was noted during the course of therapy. There was no relapse after 12 months of cessation of treatment. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.
Cyclophosphamide; haemorrhagic cystitis; hyperbaric oxygen
A retrospective study to evaluate the effect of hyperbaric oxygen (HBO2) therapy on sternal infection and osteomyelitis following median sternotomy.
Materials and methods
A retrospective analysis of patients who received sternotomy and cardiothoracic surgery which developed sternal infection and osteomyelitis between 2002 and 2009. Twelve patients who received debridement and antibiotic treatment were selected, and six of them received additional HBO2 therapy. Demographic, clinical characteristics and outcome were compared between patients with and without HBO2 therapy.
HBO2 therapy did not cause any treatment-related complication in patients receiving this additional treatment. Comparisons of the data between two study groups revealed that the length of stay in ICU (8.7 ± 2.7 days vs. 48.8 ± 10.5 days, p < 0.05), duration of invasive (4 ± 1.5 days vs. 34.8 ± 8.3 days, p < 0.05) and non-invasive (4 ± 1.9 days vs. 22.3 ± 6.2 days, p < 0.05) positive pressure ventilation were all significantly lower in patients with additional HBO2 therapy, as compared to patients without HBO2 therapy. Hospital mortality was also significantly lower in patients who received HBO2 therapy (0 case vs. 3 cases, p < 0.05), as compared to patients without the HBO2 therapy.
In addition to primary treatment with debridement and antibiotic use, HBO2 therapy may be used as an adjunctive and safe treatment to improve clinical outcomes in patients with sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.
hyperbaric oxygen; sternal infection; osteomyelitis; sternotomy; Cardiothoracic surgery
Carbon monoxide (CO) poisoning can be a life threatening condition. Systemic hyperbaric oxygen (HBO) therapy is used to induce CO detoxification. However, little is known about the hemodynamic response to HBO in severely intoxicated patients.
We retrospectively analyzed the medical records of 6 CO-poisoned patients treated with propofol, rocuronium bromide, and HBO. The HBO protocol comprised 3 HBO treatments (HBOT1 to HBOT3) within 24 hours. During all HBO sessions heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse blood pressure (ΔBP) were measured every five minutes. Non-parametric tests were used to compare data between HBO sessions.
HR increased significantly as the number of HBOT increased, from 68 beats per minute (bpm) during HBOT1 to 77 and 86 bpm during HBOT2 and HBOT3, respectively (p < 0.05). In addition, while no significant change was found for DBP, both SBP and ΔBP showed a transient and significant increase during HBOT2, compared to HBOT1, that did not return to basal values during HBOT3.
Based on previous studies that have established the respective effects of rocuronium bromide, propofol, HBO, and CO alone on HR, SBP, and ΔBP, it is concluded that the hemodynamic responses observed in the present study are likely to be due to CO. If such, given that neither HR nor SBP and ΔBP returned to basal values by the end of HBOT3, it is suggested that more than 3 HBOT sessions could be necessary to provide full hemodynamic recovery in CO-poisoned patients.
Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O2 delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe. To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004–2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.
Hyperbaric oxygen therapy; Cancer; Hypoxia
Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation.
Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined.
The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs-HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area.
This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs.
The present study aimed to evaluate the clinical efficacy of hyperbaric oxygen (HBO) treatment for depression in the convalescent stage following cerebral hemorrhage. A total of 60 cases of patients with depression in the convalescent stage following cerebral hemorrhage (2–6 months) were randomly divided into the treatment group (treated with HBO, 30 cases) and the control group (treated with Deanxit, 30 cases). Prior to treatment and at 4 weeks post-treatment, efficacy was evaluated by the Hamilton Depression Scale (HAMD) and nerve function defect scores. There was a significant difference in the total efficacy between the two groups (P<0.05), and a significant difference in the HAMD scores (P<0.05). There were also significant differences between the pre- and post-treatment HAMD scores within the two groups (both P<0.05). HBO is able to significantly improve the degree of depression in the convalescent stage following cerebral hemorrhage and also promote nerve function recovery.
cerebral hemorrhage; convalescent stage; hyperbaric oxygen; depression
This study investigates the therapeutic potential of hyperbaric oxygen therapy (HBO) in reducing hypoxia and improving engraftment of intraportal islet transplants by promoting angiogenesis.
Diabetic BALB/c mice were transplanted with 500 syngeneic islets intraportally and received six consecutive twice-daily HBO treatments (n = 9; 100% oxygen for 1 h at 2.5 atmospheres absolute) after transplantation. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) was used to assess new vessel formation at postoperative days (POD) 3, 7, and 14. Liver tissue was recovered at the same time points for correlative histology, including: hematoxylin and eosin, hypoxia-inducible factor (HIF1α), Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), vascular endothelial growth factor (VEGF), and von Willebrand Factor immunohistochemistry.
HBO therapy significantly reduced HIF-1α, TUNEL and VEGF expression in islets at POD 7. In the non-HBO transplants, liver enhancement on DCE MRI peaked at POD 7 consistent with less mature vasculature but this enhancement was suppressed at POD 7 in the HBO-treated group. The number of new peri-islet vessels at POD 7 was not significantly different between HBO and control groups.
These results are consistent with a hyperbaric oxygen-mediated decrease in hypoxia that appeared to enhance vessel maturation in the critical days following intraportal islet transplantation.
Islet transplantation; HBO treatment; HIF-1α; MRI; VEGF
Current treatments for osteochondral injuries often result in suboptimal healing. We hypothesized that the combination of hyperbaric oxygen (HBO) and fibrin would be superior to either method alone in treating full-thickness osteochondral defects.
Osteochondral repair was evaluated in 4 treatment groups (control, fibrin, HBO, and HBO+fibrin groups) at 2-12 weeks after surgical injury. Forty adult male New Zealand white rabbits underwent arthrotomy and osteochondral surgery on both knees. Two osteochondral defects were created in each femoral condyle, one in a weight-bearing area and the other in a non-weight-bearing area. An exogenous fibrin clot was placed in each defect in the right knee. Left knee defects were left empty. Half of the rabbits then underwent hyperbaric oxygen therapy. The defects in the 4 treatment groups were then examined histologically at 2, 4, 6, 8, and 12 weeks after surgery.
The HBO+fibrin group showed more rapid and more uniform repair than the control and fibrin only groups, but was not significantly different from the group receiving HBO alone. In the 2 HBO groups, organized repair and good integration with adjacent cartilage were seen at 8 weeks; complete regeneration was observed at 12 weeks.
HBO significantly accelerated the repair of osteochondral defects in this rabbit model; however, the addition of fibrin produced no further improvement.
To investigate the effects of hyperbaric oxygen (HBO2) on aggressive periodontitis (AgP), and subgingival obligate anaerobes in Chinese patients.
Materials and Methods:
Sixty cases of Chinese patients with AgP were randomly divided into two groups –the HBO2 group (30 cases) and the control group (30 cases). Study teeth were divided into four groups –: the HBO2 therapy, the HBO2 + scaling scaling group, the scaling group and the control group. Subgingival anaerobic organisms were measured with anaerobic culture, and number of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus was counted. Comparisons of changes in the clinical indices, and subgingival anaerobes were made between the groups.
Highly significant differences in gingival index (GI), probing depth (PD), attachment loss (AL), and Plaque index (PLI), and tooth odontoseisis (TO) were seen in the HBO2, the HBO2 + scaling and the scaling groups when compared with the control group (P<0.01). The number of subgingival anaerobes as well as the types of obligate anaerobes and facultative anaerobes and the number of Bacteroides melaninogenicus were reduced markedly in these three treatment groups. Highly statistical differences in clinical indices, subgingival anaerobe number and types of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus were found when comparisons were made between the HBO2 + scaling and the HBO2 groups, as well as between the HBO2 + scaling and the scaling groups. Clinical follow-ups indicated that the GI, PD, AL, TO, PLI and subgingival anaerobes number of the three therapeutic groups were reduced more severely than the control group.
HBO2 had good therapeutic effects on Chinese patients with AgP. HBO2 therapy combined with scaling and root planing was the most beneficial in the treatment of AgP. The therapeutic effect of HBO2 on AgP is most likely through inhibition of the growth of subgingival anaerobes. Clinical follow-ups suggest that the effect could last more than 2 years.
Aggressive periodontitis; Chinese; hyperbaric oxygen; subgingival anaerobes
Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome.
Sepsis; Escherichia coli; HBO; Ozone; Oxidant stress; Antioxidant.
Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood.
The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment.
Materials and methods
The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication.
The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO.
Discussion and Conclusion
CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO.
ClinicalTrials.gov identifier: NCT00280579
Background and Purpose:
We investigated the role of cyclooxygenase-2 (COX-2) in mechanisms of hyperbaric oxygen preconditioning (HBO-PC) in the mouse model of surgical brain injury (SBI).
C57BL mice were administered 100% oxygen for 1 hr at 2.5 ATA for 5 consecutive days and subjected to SBI. Neurological status and brain edema were evaluated at 24 hrs and 72 hrs after the brain insult. Fluorescent immunostaining and Western blotting were performed to study hypoxia inducible factor-1α (HIF-1α) and COX-2, respectively. Two doses of COX-2 inhibitor, NS398 (3mg/kg and 10mg/kg) were used to verify the role of COX-2 signaling pathway in the mechanism of HBO-PC.
HBO-PC improved neurological status and decreased brain edema at 24hrs and 72hrs after SBI. HBO-PC by itself and SBI independently increased COX-2 levels by 2-fold and 4-fold respectively. HBO-PC however reduced increase in HIF-1α and COX-2 expression after SBI. The HBO-PC-induced improvement in neurological status and brain edema was reversed by suboptimal dose of COX-2 inhibitor, NS398 (10mg/kg, i.p; 1/4th of dose shown to provide neuroprotection), which itself had no effect on investigated endpoints.
HBO-PC attenuates post-operative brain edema and improves neurological outcomes following SBI. The HBO-PC induced neuroprotection is mediated via COX-2 signaling pathways.
Hyperbaric Oxygen; Preconditioning; Surgical Brain Injury; Cyclooxygenase-2; Brain Edema; Neuroprotection
Hyperbaric oxygen therapy (HBOT) is used for a number of applications, including the treatment of diabetic foot ulcers and CO poisoning. However, we and others have shown that HBOT can mobilize cellular antioxidant defenses, suggesting that it may also be useful under circumstances in which tissue protection from oxidative damage is desired. To test the protective properties of hyperbaric oxygen (HBO) on a tissue level, we evaluated the ability of a preconditioning treatment regimen to protect cutaneous tissue from UV-A-induced oxidative damage. Three groups of hairless SKH1-E mice were exposed to UV-A 3 days per week for 22 weeks, with two of these groups receiving an HBO pretreatment either two or four times per week. UV-A exposure increased apoptosis and proliferation of the skin tissue, indicating elevated levels of epithelial damage and repair. Pretreatment with HBO significantly reduced UV-A-induced apoptosis and proliferation. A morphometric analysis of microscopic tissue folds also showed a significant increase in skin creasing following UV-A exposure, which was prevented by HBO pretreatment. Likewise, skin elasticity was found to be greatest in the group treated with HBO four times per week. The effects of HBO were also apparent systemically as reductions in caspase-3 activity and expression were observed in the liver. Our findings support a protective function of HBO pretreatment from a direct oxidative challenge of UV-A to skin tissue. Similar protection of other tissues may likewise be achievable.
Hyperbaric oxygen; Preconditioning; UV-A; Skin; Apoptosis; Liver; SKH1-E mice
Hyperbaric oxygen (HBO2) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-min session of HBO2 treatment produced a prolonged antinociceptive effect in mice that persisted for 90 min after cessation of treatment. The HBO2-induced antinociception was significantly attenuated by pretreatment prior to HBO2 exposure with the opioid antagonist naltrexone, the non-specific nitric oxide synthase (NOS)-inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N5-(1-iminoethyl)-L-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin1-13 but not by rabbit antisera against either β-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 min after HBO2-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 min following HBO2 treatment but prior to nociceptive testing. These findings indicate that the antinociception that persists for 90 min after HBO2 exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO2 treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO2 may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.
Hyperbaric Oxygen; Nitric Oxide; Opioid; Antinociception; Mice
Tumor hypoxia is a known driver of angiogenesis that also facilitates tumor growth. Moreover, poorly oxygenated central tumor area remains relatively radio or chemo resistant. HBO therapy is known to elevate the levels of dissolved oxygen and eliminates tumor hypoxia. It has been one of the modalities in cancer treatment; therefore its optimization is important. In this experimental study, no cancer enhancing effect was seen during the course of HBO therapy; however, post therapy there was an accelerated growth and progression of tumor. HBO treated mice lived shorter and the response to therapy was dose & tumor volume dependent. HBO therapy probably exert its effect on the cancer proliferating cells through multiple pathways such as increased DNA damage, apoptosis & geno-toxicity leading to slow cancer progression while post therapy tumorigenic effect could be due to impaired DNA repair mechanism, mutagenic effect & aneuploidy as well as altered blood supply & nutrients. Tumor growth reached plateau with time and this finding validated theoretical model predicting tumor reaching an asymptotic limit. While, marked asymmetry observed in tumor volume progression or cancer cell proliferation rate in each of the experimental C3H mouse suggested a need for an alternate small animal pre-clinical cancer therapeutic model.
HyperBaric Oxygen (HBO) therapy involves exposure to pure oxygen in a pressurized room, and it is an already well-established treatment for various conditions, including those originated by serious infections. Starting from the observation of an increased number of patients who were accessing our HBO units for diseases supported from concomitant multidrug-resistant microorganisms, as well as considering the evident clinical benefit and laboratory final outcome of those patients at the end of the treatment, aim of our study was to measure, or better define at least, if there was any interaction between a hyperbaric environment and some selected microorganisms and if those positive results were due to the increased oxygen partial pressure (pO2) value or just to the increased pressure, regardless of the fraction of inspired oxygen (FiO2) applied (21÷100%).
Design and methods
We applied various increased pO2 values in a hyperbaric environment. Our study design was tailored in four steps to answer four specific questions, ordered in a progressive process: OxyBioTest (OBT)-1,2,3, and 4. Specifically, we chose to investigate possible changes in the Minimum Inhibitory Concentration (MIC) and in the Minimum Bactericidal Concentration (MBC) of multi-resistant microorganisms after a single session of hyperbaric therapy.
OBT-1 and OBT-2 provide a semi-quantitative confirmation of the bacterio-cidal and cytostatic effects of HBO. HBO is cidal only if the total exposure pressure is elevated, and cidal or cytostatic effect are not always dependent on the pO2 applied.
OBT-4 has shown the adjuvant effect of HBO and antimicrobial drug against some selected bacteria.
We seem allowed to hypothesize that only in case of a good approach to a lesion, permitting smaller bacterial loads thanks to surgical debridement and/or eventual antibiotic therapy for example, You can observe the clear effectiveness of the HyperBaric Oxygen (HBO) exposure as a valid adjuvant therapy, even when that lesion is substained from multidrug-resistant micro-organisms. On the contrary when the bacterial load is very high we observe an unchanged situation or a just a slightly diminishing in the number of cfu/ml.
Even if confined in this ‘in vitro’ environment and in a single treatment, just knowing the microorganism strain responsible of the lesion we seem allowed to both weight the possible related effectiveness using HBO Therapy (HBOT) and derive the best pO2 to treat the case. A further possible development of the study highlights a comparison between Acinetobacter baumannii (ACBA) and Pseudomonas aeruginosa (PSAE), and Escherichia coli (ESCO) and Klebsiella pneumoniae (KLPN).
Hyperbaric; Oxygen; Microorganism; Bacteria
To report a case of radiation-induced macular ischemia where vision and macular perfusion improved after hyperbaric oxygen (HBO) therapy.
A 62-year-old male patient developed radiation-induced macular ischemia after he was treated with radiation for brain glioma. The patient presented with best spectacle-corrected visual acuity (BSCVA) acuity of 20/400 in his right eye. Optical coherence tomography (OCT) showed central macular thickness of 468 μm. The patient received focal laser, intravitreal triamcinolone, and HBO therapy.
The patient’s vision improved from 20/400 to 20/100 after focal laser and intravitreal triamcinolone. His central macular thickness improved from 468 μm to 132 μm. After receiving HBO therapy, his VA improved to 20/50 and fluorescein angiography showed improvement in macular perfusion.
HBO therapy improves macular perfusion in patients with radiation-induced macular ischemia.
macular ischemia; visual acuity; hyperbaric oxygen therapy; macular perfusion