ABSTRACT
Objective To explore the potential mechanisms underlying the prominent efficiency of hyperbaric oxygen therapy (HBOT) in the treatment of severe coronavirus disease 2019 (COVID-19) patients. Methods Five COVID-19 patients, aged from 24 to 69 years old, received HBOT after routine therapies failed to stop the deterioration and progressive hypoxemia in General Hospital of the Yangtze River Shipping. The procedure of HBOT was as follows: compressed to 2.0 ATA (0.1 MPa gauge pressure, patient 1) or 1.6 ATA (0.06 MPa gauge pressure, patient 2-5) at a constant rate for 15 min, maintained for 90 min (first treatment) or 60 min (subsequent treatment), then decompressed to normal pressure for 20 min, once a day; the patients inhaled oxygen with the mask of Built-in-Breathing System continuously; and HBOT was ended when the daily mean pulse oxygen saturation (SpO2) in wards was above 95% for two days. The symptoms, respiratory rate (RR), SpO2, arterial blood gas analysis, blood routine, coagulation function, high-sensitivity C-reactive protein (hs-CRP) and chest computed tomography (CT) were collected. Paired t test was used to compare each index before and after treatment. Results After the first HBOT, the symptoms and signs of the five patients began to improve. Supine breathlessness disappeared after HBOT for four times, and digestive tract symptoms completely disappeared and only mild chest pain and breathlessness at rest and in motion remained after HBOT for five times. After finishing HBOT, the RR of the patients was significanlty lower than that before HBOT ([20.80±2.28] min-1 vs [27.20±5.40] min-1, P0.05). Before HBOT, the arterial partial pressure of carbon dioxide (PaCO2) of the patients was (31.48±3.40) mmHg (1 mmHg=0.133 kPa), which was lower than the normal range (35-45 mmHg). After finishing HBOT, arterial partial pressure of oxygen ([130.20±18.58] mmHg), arterial oxygen saturation ([98.40±0.55]%), lymphocyte proportion (0.207 8±0.074 2) and lymphocyte count ([1.09±0.24]×109/L) were significantly higher than those before HBOT ([61.60±15.24] mmHg, [73.20±6.43]%, 0.094 6±0.062 1, and [0.61± 0.35]×109/L), while the levels of fibrinogen ([2.97±0.27] g/L) and hs-CRP ([7.76±6.95] mg/L) were significantly lower than those before HBOT ([4.45±0.94] g/L and [30.36±1.27] mg/L) (all P0.05). All the five patients had typical lung CT imaging changes of severe COVID-19 before HBOT, which were improved after HBOT. Conclusion Systemic hypoxia induced by persistent hypoxemia may be the main reason for the deterioration of severe COVID-19. The respiratory dysfunction of COVID-19 is mainly alveolar gas exchange dysfunction. HBOT may be the best way to correct the progressive hypoxemia which can not be controlled by atmospheric oxygen supply in severe COVID-19 patients. HBOT can provide enough oxygen supply for the continuous hypoxia tissues, and is beneficial to the recovery of immune function, circulatory function and stress level, so as to improve the condition of patients.
ABSTRACT
Objective: To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation (HBO)-induced central nervous system (CNS) damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods: Rats were randomly divided into the following groups: normal control, safe decompressing, fast decompressing (FD) injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme (TACE) positive cells were detected immunohistochernically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid (CSF) were determined by L929 cell cytotoxicity bioassay. Results: 1134 positive microglia appeared in rats' CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index (P<0.05). TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h; reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conclusion: Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin.