Umbilical cord-derived MSC and hyperbaric oxygen therapy effectively protected the brain in rat after acute intracerebral haemorrhage.

This study tested the hypothesis that combined therapy with human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs-HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2-5 than in group 1 (P < .001), but it did not differ among groups 2 to 5. By days 7, 14 and 28, the integrity of neurological function was highest in group 1, lowest in group 2 and significantly progressively improved from groups 3 to 5 (all P < .001). By day 28, the BHV was lowest in group 1, highest in group 2 and significantly lower in group 5 than in groups 3/4 (all P < .0001). The protein expressions of inflammation (HMGB1/TLR-2/TLR-4/MyD88/TRAF6/p-NF-κB/IFN-γ/IL-1ß/TNF-α), oxidative stress/autophagy (NOX-1/NOX-2/oxidized protein/ratio of LC3B-II/LC3B-I) and apoptosis (cleaved-capspase3/PARP), and cellular expressions of inflammation (CD14+, F4/80+) in brain tissues exhibited an identical pattern, whereas cellular levels of angiogenesis (CD31+/vWF+/small-vessel number) and number of neurons (NeuN+) exhibited an opposite pattern of BHV among the groups (all P < .0001). These results indicate that combined HUCDMSC-HBO therapy offered better outcomes after rat ICH.

Effect of self-acupressure on middle ear barotrauma associated with hyperbaric oxygen therapy: A nonrandomized clinical trial.

BACKGROUND: In hyperbaric oxygen therapy (HBOT), a patient is exposed to pure oxygen in a chamber. While HBOT is a long-standing and well-established treatment for a wide variety of medical conditions, one of the main complications is middle ear barotrauma (MEB), which can lead to complaints of ear discomfort, stuffiness or fullness in the ear, and difficulties in equalizing ear pressure. The aim of this study is to evaluate the efficacy of self-acupressure in preventing and reducing the degree of MEB associated with HBOT. METHODS: This is a prospective nonrandomized controlled study. A sample of 152 participants will be assigned to 2 groups in a 1:1 ratio. The participants in the control group will receive conventional Valsalva and Toynbee maneuvers, while those in the experimental group will be given additional self-acupressure therapy. The acupoints used will be TE17 (Yifeng), TE21 (Ermen), SI19 (Tinggong), and GB2 (Tinghui). The Modified Teed Classification, symptoms of MEB, and overall ear discomfort levels will be assessed. Data will be analyzed using the Chi-Squared test or t test. OBJECTIVES: This study aims to evaluate the efficacy of self-acupressure for preventing and reducing the degree of MEB associated with HBOT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04311437. Registered on 17 March, 2020.

S100 Calcium Binding Protein A9 Represses Angiogenic Activity and Aggravates Osteonecrosis of the Femoral Head.

Ischemic damage aggravation of femoral head collapse is a prominent pathologic feature of osteonecrosis of the femoral head (ONFH). In this regard, S100 calcium binding protein A9 (S100A9) is known to deteriorate joint integrity, however, little is understood about which role S100A9 may play in ONFH. In this study, a proteomics analysis has revealed a decrease in the serum S100A9 level in patients with ONFH upon hyperbaric oxygen therapy. Serum S100A9 levels, along with serum vascular endothelial growth factor (VEGF), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), and tartrate-resistant acid phosphatase 5b levels were increased in patients with ONFH, whereas serum osteocalcin levels were decreased as compared to healthy controls. Serum S100A9 levels were increased with the Ficat and Arlet stages of ONFH and correlated with the patients with a history of being on glucocorticoid medication and alcohol consumption. Osteonecrotic tissue showed hypovasculature histopathology together with weak immunostaining for vessel marker CD31 and von Willrbrand factor (vWF) as compared to femoral head fracture specimens. Thrombosed vessels, fibrotic tissue, osteocytes, and inflammatory cells displayed strong S100A9 immunoreactivity in osteonecrotic lesion. In vitro, ONFH serum and S100A9 inhibited the tube formation of vessel endothelial cells and vessel outgrowth of rat aortic rings, whereas the antibody blockade of S100A9 improved angiogenic activities. Taken together, increased S100A9 levels are relevant to the development of ONFH. S100A9 appears to provoke avascular damage, ultimately accelerating femoral head deterioration through reducing angiogenesis. This study provides insight into the molecular mechanism underlying the development of ONFH. Here, analysis also highlights that serum S100A9 is a sensitive biochemical indicator of ONFH.

Early Recovery of Exercise-Related Muscular Injury by HBOT.

Early recovery from muscular injury is crucial for elite athletes. Hyperbaric oxygen therapy (HBOT) has been reported to be beneficial in terms of accelerating cell recovery and tissue repair, which are considered to be helpful for eliminating fatigue and recovering stamina. This study was performed to evaluate the efficacy of HBOT for exercise-related muscular injury. Forty-one athletes with exercise-related muscular injuries were recruited and randomized into an HBOT group and a control group. All participants received 10 sessions of either HBOT or placebo treatment. The brief pain inventory (BPI) was completed, and serum samples were analyzed. Data were collected before treatment (T1), at the end of the fifth treatment session (T2), at the end of the tenth treatment session (T3), and two weeks after T3 (T4). At T3, the HBOT group showed prominent reductions in the levels of creatine phosphokinase (CK), glutamic oxaloacetate transaminase (GOT), and myoglobin (MB), which lasted until T4. However, the control group did not present any statistical differences in levels from T1 to T4. In terms of pain intensity and interference, the HBOT group showed significant improvements at T3, while no improvements were observed in the control group. In conclusion, HBOT facilitates the early recovery of exercise-related muscular injury. This trial is registered with ISRCTN17817041.

Hyperbaric oxygen facilitates the effect of endothelial progenitor cell therapy on improving outcome of rat critical limb ischemia.

We tested the hypothesis that hyperbaric oxygen (HBO) (100% oxygen/2.4 atmospheres) facilitated the effect of autologous endothelial progenitor cell (EPC) therapy on restoring the blood flow in rat critical-limb ischemia (CLI). Adult-male-SD rats (n = 8/each group) were categorized into group 1 [sham control (SC)], group 2 (CLI-treated with culture medium), group 3 [CLI-intermittent HBO (3 h/day for 5 consecutive days after CLI), group 4 (CLI-EPC/2.0 × 106 cells), and group 5 (CLI-HBO-EPC). By day 5 after CLI, flow cytometry showed that the circulating EPC (Sca-1/CD31+/C-kit/CD31+/CD34+) levels were highest in group 5 and lowest in group 2 (all P < 0.001). By day 14, laser Doppler demonstrated that the ratio of blood flow (i.e., CLI to normal hind-limb) was highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3 and 4 (all P < 0.0001). The protein expressions of endothelial-cell biomarkers (CD31/vWF/eNOS), and numbers of endothelial-cell markers (CD31+/vWF+) and small vessels exhibited a similar pattern to blood-flow ratio among five groups, whereas the angiogenesis parameters in protein (CXCR4/SDF-1α/HIF-1α/VEGF) and cellular (HIF-1α/SDF-1α/CXCR4+) levels were progressively increased from groups 1 to 5 (all P < 0.0001). The protein expression of apoptotic (mitochondrial-Bax/cleaved-capspase-3/PARP), fibrotic (p-Smad3/TGF-ß) and mitochondrial-damaged (cytosolic-cytochrome C) exhibited an opposite pattern, whereas the protein expressions of anti-fibrotic (BMP-2/p-Smad1/5) and mitochondrial integrity (mitochondrial-cytochrome C) exhibited an identical pattern of ratio of blood flow among the five groups (all P < 0.0001). Combined HBO-EPC therapy is superior to either one alone in improving ischemia in rodent CLI.

Hyperbaric Oxygen Therapy Enhanced Circulating Levels of Endothelial Progenitor Cells and Angiogenesis Biomarkers, Blood Flow, in Ischemic Areas in Patients with Peripheral Arterial Occlusive Disease.

BACKGROUND: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). METHODS: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. RESULTS: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34⁺/CD133⁺/CD45dim, CD31⁺/CD133⁺/CD45dim, CD34⁺) and soluble angiogenesis factors-vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1α/HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p < 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. CONCLUSIONS: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area.

Increased circulating endothelial progenitor cells and improved short-term outcomes in acute non-cardioembolic stroke after hyperbaric oxygen therapy.

BACKGROUND: Acute ischemic stroke is a leading cause of mortality and long-term disability, and profiles of endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment. This study tested the hypothesis that hyperbaric oxygen therapy (HBOT) both improves the clinical short-term outcomes and increases the number of circulating EPCs and antioxidant capacity. METHODS: The numbers of circulating EPCs [CD133+/CD34+ (%), KDR+/CD34+ (%)], biomarkers for oxidative stress (thiols and thiobarbituric acid-reactive substances), and clinical scores (National Institutes of Health Stroke Scale [NIHSS], Barthel index [BI], and modified Rankin Scale [MRS]) were prospectively evaluated in 25 patients with acute non-cardioembolic stroke under HBOT at two time points (pre- and post-HBOT). The biomarkers and clinical scores were compared with those of 25 age- and sex-matched disease controls. RESULTS: The numbers of KDR+/CD34+ (%) in the HBOT group following HBOT increased significantly, whereas the numbers of CD133+/CD34+ (%) also showed a tendency to increase without statistical significance. The mean high-sensitivity C-reactive protein levels showed significant decrease post-HBOT follow-up in the HBOT group. The changes in KDR+/CD34+EPC (%) numbers were positively correlated with changes in clinical outcomes scores (BI, NIHSS, and MRS) in the HBOT group. CONCLUSIONS: Based on the results of our study, HBOT can both improve short-term clinical outcomes and increase the number of circulating EPCs in patients with acute non-cardioembolic stroke.

Adjunctive Hyperbaric Oxygen Therapy for Healing of Chronic Diabetic Foot Ulcers: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the effect of standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care alone on wound healing, markers of inflammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life in patients with diabetic foot ulcers (DFUs). DESIGN: Prospective, randomized, open-label, controlled study. SUBJECTS AND SETTING: The sample comprised 38 patients with nonhealing DFUs who were deemed poor candidates for vascular surgery. Subjects were randomly allocated to an experimental group (standard care plus HBOT, n = 20) or a control group (standard care alone, n = 18). The study setting was a medical center in Kaohsiung City, Taiwan. METHODS: Hyperbaric oxygen therapy was administered in a hyperbaric chamber under 2.5 absolute atmospheric pressure for 120 minutes; subjects were treated 5 days a week for 4 consecutive weeks. Both groups received standard wound care including debridement of necrotic tissue, topical therapy for Wagner grade 2 DFUs, dietary control and pharmacotherapy to maintain optimal blood glucose levels. Wound physiological indices were measured and blood tests (eg, markers of inflammation) were undertaken. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short Form. RESULTS: Complete DFU closure was achieved in 5 patients (25%) in the HBOT group (n = 20) versus 1 participant (5.5%) in the routine care group (n = 18) (P = .001). The amputation rate was 5% for the HBOT group and 11% for the routine care group (χ = 15.204, P = .010). The HBOT group showed statistically significant improvements in inflammation index, blood flow, and health-related quality of life from pretreatment to 2 weeks after the last therapy ended (P < .05). Hemoglobin A1c was significantly lower in the HBOT group following treatment (P < .05) but not in the routine care group. CONCLUSIONS: Adjunctive HBOT improved wound healing in persons with DFU. Therapy also reduced the risk of amputation of the affected limb. We assert that at least 20 HBOT sessions are required to be effective.

Comparison of intratympanic steroid injection, hyperbaric oxygen and combination therapy in refractory sudden sensorineural hearing loss.

OBJECTIVE: The objective of this study was to compare the efficacy of intratympanic steroid injection (ITS), hyperbaric oxygen (HBO), and combination therapy as salvage treatment in patients with sudden sensorineural hearing loss (SSNHL) after failure of systemic therapy. STUDY DESIGN: A historical cohort study. SETTING: Academic medical center. SUBJECTS AND METHODS: One hundred three refractory SSNHL patients are enrolled. Among them, 35 received ITS alone (ITS group), 22 received HBO alone (HBO group), 19 received combined ITS and HBO (combined group), and 27 received no salvage therapies (control group). Hearing outcomes were determined by hearing gains in pure-tone average (PTA), recovery rate, and word recognition score (WRS) measured by audiometry before and after salvage therapies. RESULTS: Significant larger hearing gains in PTA were found in the ITS, HBO, and combined groups than the control group. The combination of ITS and HBO resulted in a significantly larger WRS improvement than the control group (p = 0.035) and larger hearing gains than the ITS and HBO groups in 250 Hz (p < 0.05). CONCLUSION: ITS, HBO, and combined therapy offered some benefits in hearing improvement. Combined ITS/HBO may result in a larger WRS improvement and recovery of hearing, especially in lower frequencies. Further randomized prospective studies are needed for confirmation.

Treatment of diabetic foot ulcers: a comparative study of extracorporeal shockwave therapy and hyperbaric oxygen therapy.

OBJECTIVE: This study compared the effectiveness of extracorporeal shockwave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) in chronic diabetic foot ulcers. PATIENTS AND METHODS: The ESWT group (39 patients/44 feet) received shockwave therapy twice per week for total six treatments. The HBOT group (38 patients/40 feet) received hyperbaric oxygen therapy daily for total 20 treatments. Evaluations included clinical assessment, blood flow perfusion scan and histopathological examination. RESULTS: The overall clinical results showed completely healed ulcers in 57% and 25% (P = 0.003); ≥ 50% improved ulcers in 32% and 15% (P = 0.071); unchanged ulcers in 11% and 60% (P < 0.001) and none worsened for the ESWT and the HBOT group respectively. The blood flow perfusion rates were comparable between the two groups before treatment (P = 0.245), however, significant differences were noted after treatment favoring the ESWT group (P = 0.002). Histopathological examination revealed considerable increases in cell proliferation and decreases in cell apoptosis in the ESWT group as compared to the HBOT group. CONCLUSION: ESWT is more effective than HBOT in chronic diabetic foot ulcers. ESWT-treated ulcers showed significant improvement in blood flow perfusion rate and cell activity leading to better healing of the ulcers relative to HBOT in chronic diabetic foot ulcers.

Extracorporeal shockwave treatment for chronic diabetic foot ulcers.

BACKGROUND: This prospective study compared extracorporeal shockwave treatment (ESWT) with hyperbaric oxygen therapy (HBO) in chronic diabetic foot ulcers. PATIENTS AND METHODS: Seventy-two patients with 72 chronic diabetic foot ulcers were randomly divided into two groups of similar demographics with 34 patients with 36 ulcers in the ESWT group and 36 patients with 36 ulcers in the HBO group. Patients in the ESWT group received 300 + 100/cm(2) impulses of shockwave at 0.11 mJ/cm(2) energy flux density every 2 wk for 6 wk, whereas patients in the HBO group received HBO daily for 20 treatments. The evaluations included clinical assessment of the ulcers with photo-documentation, blood flow perfusion scan, bacteriological examination, histological study, and immunohistochemical analysis. RESULTS: The overall results showed completely healed in 31%, improved in 58%, and unchanged in 11% for the ESWT group and 22% completely healed, 50% improved, and 28% unchanged for the HBO group. The ESWT group showed significantly better clinical results and local blood flow perfusion, higher cell concentration, and activity than the HBO group. On immunohistochemical analysis, the ESWT group demonstrated significant increases in endothelial nitric oxide synthase, vessel endothelial growth factor, and proliferation cell nuclear antigen expressions and a decrease in transference-mediated digoxigenin-deoxy-UTP nick end-labeling expression than the HBO group. CONCLUSIONS: ESWT appears to be more effective than HBO in chronic diabetic foot ulcers.