Hyperbaric oxygen treatment reverses radiation induced pro-fibrotic and oxidative stress responses in a rat model.

PURPOSE: Radiotherapy is effective in the treatment of tumors in the pelvic area but is associated with side effects such as cystitis and proctitis. Hyperbaric Oxygen Therapy (HBOT) has emerged as a treatment modality for radiation-induced side effects. In a rat model for radiation cystitis, we studied the effects of HBOT on oxidative stress and pro-fibrotic factors. MATERIALS AND METHODS: Sedated Sprague-Dawley rats underwent bladder irradiation of 20Gy with and without 20 sessions of HBOT during a fortnight. Control animals were treated with and without HBOT. All four groups of animals were euthanized 28 days later. Histopathological examinations, immunohistochemistry and quantitative polymerase chain reaction (qPCR) were used to analyze changes in oxidative stress (8-OHdG), anti-oxidative responses (SOD-1, SOD2, HO-1 and NRFα) and a panel of Th1-type and Th2-type cytokines (IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α, TGF-ß, IFN-γ) in the urinary bladder. RESULTS: Bladder irradiation increased the expression of 8-OHdG, SOD2, HO-1, NRFα, IL-10, TNF-α and tended to increase TGF-ß. These changes were completely reversed by HBOT while HBOT in control animals had no effects on the studied markers for oxidative stress, anti-oxidative responses and Th1-type and Th2-type cytokines. CONCLUSIONS: Radiation induced a significant elevation of oxidative stress, antioxidants and pro-fibrotic factors in our animal model for radiation cystitis that were completely reversed and normalized by HBOT. Our findings indicate that HBOT may prevent radiation-induced changes by affecting oxidative stress and inflammatory cascades induced by radiation. SUMMARY: Radiotherapy may cause the development of chronic inflammation and fibrosis, significantly impairing organ function. We hypothesized that bladder irradiation induces an oxidative stress reaction, thereby triggering the redox system and thus initiating an inflammatory and pro-fibrotic response. We aimed to assess whether these changes would be reversed by hyperbaric oxygen using an animal model for radiation cystitis. Our study show that hyperbaric oxygen therapy may reverse oxidative stress and pro-inflammatory factors induced by radiation.

Hyperbaric oxygen in the treatment of postoperative infections in paediatric patients with neuromuscular spine deformity.

The aim of this study is to evaluate possible benefits of hyperbaric oxygen (HBO) therapy in the treatment of deep postoperative infections in six high risk paediatric patients with neuromuscular spine deformity. The study involved review of medical records including radiology, office visits, and telephone contacts for six patients, referred for postoperative HBO therapy in 2003-2005. Infection control and healing without removal of implants or major revision surgery with a minimum of 2-year follow-up after index surgery were considered to represent success. All infections were resolved. Median time for wound healing, normalisation of blood tests and antibiotic weaning were 3 months. Radiological bony fusion, intact implants without any signs of radiolucent zones were seen in all cases at a mean follow-up of 54 months (37-72). Side effects of HBO treatment were minor. HBO is a safe and potentially useful adjuvance in the treatment of early deep postoperative infections in complex situations with spinal implants in high risk paediatric patients.

Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study.

Sixteen patients, 12 with episodic and four with chronic cluster headache (CH) according to the International Headache Society criteria (1), participated in the study. They were randomly selected to start with one out of two different hyperbaric treatments in a double-blind, placebo-controlled, cross-over study design. Both gases were administered by mask inside a multiplace hyperbaric chamber for 70 min at 250 kPa (2.5 ATA) in two sessions 24 h apart. Active treatment was 100% oxygen (HBO treatment), while placebo treatment was 10% oxygen in nitrogen (hyperbaric normoxic placebo = sham treatment) corresponding to breathing air at sea level. All patients were decompressed on air. The patients documented the number of headache attacks and their degree of severity according to a modified VAS scale (level 0-4, where level 0 = no headache and level 4 = very severe headache). A headache index (HI = sum of (number of attacks times degree of severity)) was calculated for the run-in week prior to and the week after each separate treatment. A treatment was regarded as effective if it reduced the HI by>50%. Blood samples were taken from the external jugular vein before and during hyperbaric treatment (after 30 and 70 min), 1 day and 1 week after each treatment for analyses of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) and in a few patients also endotheline and nitrate. No difference between HBO and sham treatment on the HI or the prophylactic effect was observed in our study. However, 83% of the episodic CH patients and 25% of the chronic ones responded to either of the two treatments with at least 50% reduction of HI or remission for shorter or longer periods. This response rate exceeds an expected high placebo response due to the study procedure. Two episodic CH patients still experienced remission on follow-up 1 year after sham treatment. Five patients reported mild or moderate CH attacks during the sham treatment, and none during the HBO treatment. Changes in neuropeptides, endotheline and nitrate levels did not differ systematically when comparing the two different hyperbaric treatments or with respect to responders and non-responders. We conclude that two HBO sessions were not more effective than two sham treatments in reducing the HI and interrupting the CH period when given in a well-established cluster period or in chronic CH. The hyperbaric condition itself seems effective in reducing the HI, at least in patients with episodic CH, although a powerful placebo response can not be ruled out.

Hyperbaric oxygen therapy for wound complications after surgery in the irradiated head and neck: a review of the literature and a report of 15 consecutive patients.

BACKGROUND: Radiotherapy, which is often used for cancer in the head and neck, leads to damage of tissue cells and vasculature. Surgery in such tissues has an increased complication rate, because wound healing requires angiogenesis and fibroplasia as well as white blood cell activity, all of which are jeopardized. Hyperbaric oxygen therapy (HBO) raises oxygen levels in hypoxic tissue, stimulates angiogenesis and fibroplasia, and has antibacterial effects. METHODS: In this consecutive retrospective study, 15 patients with soft-tissue wounds without signs of healing after surgery in full-dose (64 Gy) irradiated head and neck regions were treated with HBO and adjuvant therapy. The patients in this study were also compared with patients examined in an earlier study, with corresponding wounds treated without HBO. RESULTS: The healing processes seemed to be initiated and accelerated by HBO. In the HBO group, 12 of 15 patients healed completely, 2 patients healed partially, and only 1 patient did not heal at all. There were no life-threatening complications. In the reference group, only 7 of 15 patients with corresponding wounds without signs of healing eventually healed without surgical intervention, and 2 patients had severe postoperative hemorrhage, which in one case was fatal. CONCLUSION: Evaluation of obtained results supports the hypothesis that HBO therapy has a clinically significant effect on initiation and acceleration of healing processes in irradiated soft tissues.

Role of airway resistance in the control of ventilation during exercise.

To analyze the interdependence of respiratory drive, ventilation and airway resistance during exercise, mouth occlusion pressure (P0.1), minute ventilation (V) and mean inspiratory flow (VT/TI) were studied in eight normal subjects performing cycle-ergometer exercise at loads ranging from 0 W to 200 W under two different ambient conditions: 1) during oxygen breathing at 1.3 ATA, and 2) during air breathing at 6 ATA (PO2 = 1.3 ATA). Comparison of measurements at 6 ATA with those at 1.3 ATA indicated that a 4.2-fold increase in respired gas density (D) had little or no influence on the V and VT/TI responses whereas P0.1 at any given VT/TI was increased by a factor of 1.9. In both conditions, P0.1 increased at a faster rate than VT/TI as the work load increased. At loads higher than 40 W, the relationship between P0.1, D and VT/TI was found to approximate the equation P0.1 = K X D0.5(VT/TI)1.4, where K is a constant that varies among subjects. The results indicate that the ratio P0.1/(VT/TI), an estimate of respiratory impedance, increased with both D and VT/TI. Evidence is presented that the respiratory drive was reflexly enhanced in response to loading as airway resistance increased with D and/or VT/TI. We conclude that neural mechanisms compensating for internal flow-resistive loading play an important role in the control of ventilation during exercise, both at normal and at raised air pressures.