MDPIActa Medica Okayama2227-90591212024Hydrogen in Transplantation: Potential Applications and Therapeutic Implications118ENTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTakashiHongoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityKoheiAgetaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityToshiyukiAokageDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMasakiHisamuraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityHydrogen gas, renowned for its antioxidant properties, has emerged as a novel therapeutic agent with applications across various medical domains, positioning it as a potential adjunct therapy in transplantation. Beyond its antioxidative properties, hydrogen also exerts anti-inflammatory effects by modulating pro-inflammatory cytokines and signaling pathways. Furthermore, hydrogen's capacity to activate cytoprotective pathways bolsters cellular resilience against stressors. In recent decades, significant advancements have been made in the critical medical procedure of transplantation. However, persistent challenges such as ischemia-reperfusion injury (IRI) and graft rejection continue to hinder transplant success rates. This comprehensive review explores the potential applications and therapeutic implications of hydrogen in transplantation, shedding light on its role in mitigating IRI, improving graft survival, and modulating immune responses. Through a meticulous analysis encompassing both preclinical and clinical studies, we aim to provide valuable insights into the promising utility of hydrogen as a complementary therapy in transplantation.No potential conflict of interest relevant to this article was reported.SAGE PublicationsActa Medica Okayama1721-727X212023Hydrogen gas treatment improves survival in a rat model of crush syndrome by ameliorating rhabdomyolysisENTetsuyaYumotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshiyukiAokageDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakahiroHirayamaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirotsuguYamamotoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakafumiObaraDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTsuyoshiNojimaDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiromichiNaitoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAtsunoriNakaoDepartment of Emergency, Critical Care, and Disaster Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityObjectives: Crush syndrome (CS) is characterized by a systemic manifestation of traumatic rhabdomyolysis, leading to multiple organ dysfunction and death. Ischemia-reperfusion (IR) injury is commonly responsible for systemic response. Extending studies have shown that hydrogen gas treatment ameliorated IR injury in numerous experimental models; however, its effect on CS has not been well examined. This study aimed to investigate the effects of hydrogen gas inhalation following crush injury in an experimental model of CS.<br>
Methods: Male Sprague-Dawley rats were subjected to experimental CS by applying a total of 3.0 kg weight to both hindlimb under general anesthesia for 6 h. Immediately after decompression, the animals were randomly placed in a gas chamber filled with either air or 1.3% hydrogen gas. Animals were sacrificed 18 h or 24 h following gas exposure for non-survival studies or for survival study, respectively.<br>
Results: The rats with hydrogen treatment (n = 6) had a higher 24-h survival than the rats with air treatment (n = 9) (100% vs. 44%, p = 0.035). Lactate concentrations (2.9 +/- 0.2 vs. 2.2 +/- 0.2 mmol/L, p = 0.040) and creatine kinase (34,178 +/- 13,580 vs. 5005 +/- 842 IU/L, p = 0.016) were lower in the hydrogen group compared with the air group 18 h after decompression (n = 4 in the air group, and n = 5 in the H-2 group). Histological analysis revealed that the damage to the rectus femoris muscle and kidney appeared to be ameliorated by hydrogen treatment.<br>
Conclusion: Hydrogen gas inhalation may be a promising therapeutic approach in the treatment of CS.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1471-24662112021The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, and lung function in mice with bleomycin-induced lung injury339ENToshiyukiAokageDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMizukiSeyaDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroHirayamaDepartment of Disaster Medicine and Management, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTsuyoshiNojimaDepartment of Primary Care and Medical Education, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasumiIketaniDepartment of Biological Process of Aging, Tokyo Metropolitan Institute of GerontologyMichikoIshikawaDepartment of Emergency, Disaster and Critical Care Medicine, Hyogo College of MedicineYasuhiroTerasakiDepartment of Analytic Human Pathology, Nippon Medical SchoolAkihikoTaniguchiDepartment of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuakiMiyaharaDepartment of Medical Technology, Okayama University Graduate School of Health SciencesAtsunoriNakaoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesIkurohOhsawaDepartment of Biological Process of Aging, Tokyo Metropolitan Institute of GerontologyHiromichiNaitoDepartment of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground : Acute respiratory distress syndrome, which is caused by acute lung injury, is a destructive respiratory disorder caused by a systemic inflammatory response. Persistent inflammation results in irreversible alveolar fibrosis. Because hydrogen gas possesses anti-inflammatory properties, we hypothesized that daily repeated inhalation of hydrogen gas could suppress persistent lung inflammation by inducing functional changes in macrophages, and consequently inhibit lung fibrosis during late-phase lung injury. <br>
Methods : To test this hypothesis, lung injury was induced in mice by intratracheal administration of bleomycin (1.0 mg/kg). Mice were exposed to control gas (air) or hydrogen (3.2% in air) for 6 h every day for 7 or 21 days. Respiratory physiology, tissue pathology, markers of inflammation, and macrophage phenotypes were examined. <br>
Results : Mice with bleomycin-induced lung injury that received daily hydrogen therapy for 21 days (BH group) exhibited higher static compliance (0.056 mL/cmH(2)O, 95% CI 0.047-0.064) than mice with bleomycin-induced lung injury exposed only to air (BA group; 0.042 mL/cmH(2)O, 95% CI 0.031-0.053, p = 0.02) and lower static elastance (BH 18.8 cmH(2)O/mL, [95% CI 15.4-22.2] vs. BA 26.7 cmH(2)O/mL [95% CI 19.6-33.8], p = 0.02). When the mRNA levels of pro-inflammatory cytokines were examined 7 days after bleomycin administration, interleukin (IL)-6, IL-4 and IL-13 were significantly lower in the BH group than in the BA group. There were significantly fewer M2-biased macrophages in the alveolar interstitium of the BH group than in the BA group (3.1% [95% CI 1.6-4.5%] vs. 1.1% [95% CI 0.3-1.8%], p = 0.008). <br>
Conclusions The results suggest that hydrogen inhalation inhibits the deterioration of respiratory physiological function and alveolar fibrosis in this model of lung injury.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6862014Mean Lung Pressure during Adult High-Frequency Oscillatory Ventilation: An Experimental Study Using a Lung Model323329ENTakahiroHirayamaOsamuNaganoNaokiShibaTetsuyaYumotoKeijiSatoMichihisaTeradoToyomuUgawaShingoIchibaYoshihitoUjikeOriginal Article10.18926/AMO/53021In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance:
19.3ml/cmH<sub>2</sub>O) with or without a resistor (20cmH<sub>2</sub>O/l/sec). The ventilator settings were as follows:
mean airway pressure (MAP), 30cmH2O;frequency, 5-15Hz (every 1Hz);airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6662012Evaluating the Need for and Effect of Percutaneous Transluminal Angioplasty on Arteriovenous Fistulas by Using Total Recirculation Rate per Dialysis Session (“Clearance Gap”)443447ENToyomuUgawaKazufumiSakuramaTakashiYorifujiMunenoriTakaokaYasuhiroFujiwaraNarutoshiKabashimaDaisukeAzumaTakahiroHirayamaKoheiTsukaharaSunaoMorisadaAtsuyoshiIidaKeitaroTadaNaokiShibaNobuoSatoShingoIchibaKoichiKinoMasakiFukushimaYoshihitoUjikeOriginal Article10.18926/AMO/49040The functioning of an arteriovenous fistula (AVF) used for vascular access during hemodialysis has been assessed mainly by dilution methods. Although these techniques indicate the immediate recirculation rate, the results obtained may not correlate with Kt/V. In contrast, the clearance gap (CL-Gap) method provides the total recirculation rate per dialysis session and correlates well with Kt/V. We assessed the correlation between Kt/V and CL-Gap as well as the change in radial artery (RA) blood flow speed in the fistula before percutaneous transluminal angioplasty (PTA) in 45 patients undergoing continuous hemodialysis. The dialysis dose during the determination of CL-Gap was 1.2 to 1.4 Kt/V. Patients with a 10% elevation or more than a 10% relative increase in CL-Gap underwent PTA (n=45), and the values obtained for Kt/V and CL-Gap before PTA were compared with those obtained immediately afterward. The mean RA blood flow speed improved significantly (from 52.9 to 97.5cm/sec) after PTA, as did Kt/V (1.07 to 1.30) and CL-Gap (14.1% to -0.2%). A significant correlation between these differences was apparent (r=-0.436 and p=0.003). These findings suggest that calculating CL-Gap may be useful for determining when PTA is required and for assessing the effectiveness of PTA, toward obtaining better dialysis.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6642012Humidification of Base Flow Gas during Adult High-Frequency Oscillatory Ventilation:An Experimental Study Using a Lung Model335341ENNaokiShibaOsamuNaganoTakahiroHirayamaShingoIchibaYoshihitoUjikeOriginal Article10.18926/AMO/48688In adult high-frequency oscillatory ventilation (HFOV) with an R100 artificial ventilator, exhaled gas from patientʼs lung may warm the temperature probe and thereby disturb the humidification of base flow (BF) gas. We measured the humidity of BF gas during HFOV with frequencies of 6, 8 and 10Hz, maximum stroke volumes (SV) of 285, 205, and 160ml at the respective frequencies, and, BFs of 20, 30, 40l/min using an original lung model. The R100 device was equipped with a heated humidifier, HummaxⅡ, consisting of a porous hollow fiber in circuit. A 50-cm length of circuit was added between temperature probe (located at 50cm proximal from Y-piece) and the hollow fiber. The lung model was made of a plastic container and a circuit equipped with another HummaxⅡ. The lung model temperature was controlled at 37℃. The HummaxⅡ of the R100 was inactivated in study-1 and was set at 35℃ or 37℃ in study-2. The humidity was measured at the distal end of the added circuit in study-1 and at the proximal end in study-2. In study-1, humidity was detected at 6Hz (SV 285ml) and BF 20l/min, indicating the direct reach of the exhaled gas from the lung model to the temperature probe. In study-2 the absolute humidity of the BF gas decreased by increasing SV and by increasing BF and it was low with setting of 35℃. In this study setting, increasing the SV induced significant reduction of humidification of the BF gas during HFOV with R100.No potential conflict of interest relevant to this article was reported.