Intermittent short‐duration reoxygenation protects against simulated high altitude‐induced pulmonary hypertension in rats

Liu, Qiang; Bai, Yuxiang; Cheng, Jiu-Hua; Liu, Huan; Li, Shaohua; Yang, Jing; Wang, Zhongchao; Ma, Yan; Jiang, Min; Dong, Dong; Yan, Yi-Shang; Shi, Qingqing; Ren, Xue; Ma, Jing

doi:10.1096/fj.202000533rr

Cited by 7 publications

(8 citation statements)

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“…It could be because the occurrence and progression of HADA involve damage from hypoxia and reoxygenation leading to respiratory, haematological and cardiovascular system abnormalities that are observed in highlanders when they return to lower altitudes 34. In addition, with reoxygenation, the PaO 2 increases, and hypoxia and reoxygenation injury can induce oxidative stress-related homeostatic dysregulation, which can activate many signalling pathways in neurons and endothelial cells, thus causing a series of lung injuries, especially atelectasis 35 36. Therefore, during general anaesthesia, the positive pressure ventilation and the use of muscle relaxants enhance alveolar collapse at the end of expiration, especially during long-time operation, which eventually leads to PPCs.…”

Section: Discussionmentioning

confidence: 99%

Positive end-expiratory pressure and risk of postoperative pulmonary complications in patients living at high altitudes and undergoing surgery at low altitudes: a single-centre, retrospective observational study in China

et al. 2022

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ObjectivesTo examine whether a high positive end-expiratory pressure (PEEP ≥5 cmH2O) has a protective effect on the risk of postoperative pulmonary complications (PPCs) in a cohort of patients living at high altitudes and undergoing general anaesthesia.DesignRetrospective, observational study.SettingA tertiary hospital in China.ParticipantsAdult Tibetan patients living at high altitudes (≥3000 m) and who went to the low-altitude plain to undergo non-cardiothoracic surgery under general anaesthesia, from January 2018 to April 2020.MeasurementsThis study included 1905 patients who were divided according to the application of an intraoperative PEEP: low PEEP (<5 cmH2O, including 0 cmH2O) or high PEEP (≥5 cmH2O). The primary outcome was a composite of PPCs within the first 7 postoperative days. The secondary outcomes included reintubation and unplanned intensive care unit (ICU) admission within the first 7 postoperative days and total hospital stays (day).ResultsThe study included 1032 patients in the low PEEP group and 873 in the high PEEP group. There were no differences in the incidence of PPCs between the high and low PEEP groups (relative risk (RR) 0.913; 95% CI 0.716 to 1.165; p=0.465). After propensity score matching, 643 patients remained in each group, and the incidence of PPCs in the low PEEP group (18.0%) was higher than in the high PEEP group (13.7%; RR 0.720; 95% CI 0.533 to 0.974; p=0.033). There were no differences in the incidence of reintubation, unplanned ICU admission or hospital stays. The risk factors of PPCs derived from multiple regression showed that the application of >5 cmH2O PEEP during intraoperative mechanical ventilation was associated with a significantly lower risk of PPCs in patients from a high altitude (OR=0.725, 95% CI 0.530 to 0.992; p=0.044).ConclusionsThe application of PEEP ≥5 cmH2O during intraoperative mechanical ventilation in patients living at high altitudes and undergoing surgery at low altitudes may be associated with a lower risk of PPCs. Prospective longitudinal studies are needed to further investigate perioperative lung protection ventilation strategies for patients from high altitudes.Trial registration numberChinese Clinical Trial Registry (ChiCTR2100044260).

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Section: Discussionmentioning

confidence: 99%

Positive end-expiratory pressure and risk of postoperative pulmonary complications in patients living at high altitudes and undergoing surgery at low altitudes: a single-centre, retrospective observational study in China

et al. 2022

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“…Another study recently found that compared with low-altitude residents, high-altitude patients demonstrated enhanced tolerance to inflammation and responses to I/R injury when undergoing a primary mitral valve procedure (4). To date, most experimental animal models of hypoxia have included exposure to a hypobaric chamber to simulate physiology at equivalent altitudes (30)(31)(32)(33). However, there are differences between simulated and natural highaltitude environments, such as physical activity factors and the intermittent nature of hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of a chronic hypobaric hypoxic environment at high altitude on cardiotoxicity induced by doxorubicin in rats: a 7 T magnetic resonance study

Wan¹,

Zhu²,

He³

et al. 2022

Quant Imaging Med Surg

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Background: Doxorubicin (DOX)-induced cardiotoxicity (DIC), a major clinical problem, has no effective preventive therapies. We hypothesized that left ventricular (LV) systolic function would be improved in a chronic hypobaric hypoxia environment at high altitude. The purpose of this study was to investigate whether cardiovascular magnetic resonance could reveal the cardioprotective effect of chronic hypobaric hypoxia on DIC.Methods: In total, 60 rats were randomly assigned to 1 of 6 groups (n=10 per group): the P group (plain), PD group (plain + DOX), HH group (high altitude), HHD4 group (high altitude + DOX for 4 weeks), HHD8 group (high altitude + DOX for 8 weeks), and HHD12 group (high altitude + DOX for 12 weeks). The rats were transported to either Yushu (altitude: 4,250 m) or Chengdu (altitude: 500 m) where they underwent intraperitoneal injection of DOX (5 mg/kg/week for 3 weeks) or saline. Preclinical 7 T cardiovascular magnetic resonance was performed at weeks 4, 8, and 12. Tissue tracking was used to measure LV cardiac function and to analyze global and segmental strains. Subsequently, histological and oxidative stress tests were performed to evaluate the protective effect of a high-altitude environment on DIC. Results:The left ventricular ejection fraction (LVEF) and global and regional strains in the middle, apical, anterior, septal, inferior, and lateral segments (all P<0.05) were improved in the HHD4 group compared with the PD group. The global strain was significantly greater in absolute value in the HHD8 and HHD12 groups than in the HHD4 group (all P<0.05). Additionally, histological and enzyme-linked immunosorbent assay evaluations supported the in vivo results.Conclusions: A chronic hypobaric and hypoxic environment at high altitude partially prevented cardiac dysfunction and increased global and regional strain in DIC rat models, thereby minimizing myocardial injury and fibrosis. In addition, by increasing the total duration of chronic hypobaric hypoxia, the global strain was further increased, which was likely due to reduced oxidative stress.

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“…Cardiac tissues show an improved cardiac muscle fibres appearance with a striated arrangement of Z and H bands and reduced structural remodeling of cardiac muscle cells that occurred under hypoxia. Data showed that RNA sequencing identified the specific genes and molecular pathways that mediate the protective effects ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

“…We set the re-oxygenation level to 0 m, the duration of each session to 1 h, and the frequency to two, three, and six times each day after a 2-week treatment ( 21 ). The authors added that wash off CO 2 , H 2 O, and NH 3 , the hypobaric chamber was continually flooded with room air or 42 per cent O 2 -58 per cent N 2 .…”

Section: Methodsmentioning

confidence: 99%

Intermittent Short-Duration Re-oxygenation Attenuates Cardiac Changes in Response to Hypoxia: Histological, Ultrastructural and Oxidant/Antioxidant Parameters

Shati¹,

Zaki²,

Alqahtani³

et al. 2022

Br J Biomed Sci

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Context: Intermittent short-duration re-oxygenation attenuates cardiac changes in response to hypoxia.Objective: To see if intermittent short-duration re-oxygenation may protect the heart muscle from hypoxia damage.Materials and Methods: Eighteen albino rats were used to carry out the study. Rats divided into: (normoxia); rats exposed to room air as a control, second (hypoxic) group; rats subjected to a pressure of 405 mmHg in a hypobaric chamber to simulate hypoxia at 5,000 m, and third (intermittent short-duration re-oxygenation); rats exposed to room air three times per day. Experiments were all 14 days long.Results: Hypoxia enhanced the oxidative stress biomarker malondialdehyde while lowering the antioxidant superoxide dismutase . The levels of tumour necrosis factor (TNF-α) and interleukin-6 (IL-6) in the myocardium were elevated in hypoxic hearts. The hypoxic rats’ cardiac myofibrils showed disarray of muscle fibres, vacuolation of the sarcoplasm, pyknosis of the nucleus, and expansion of intercellular gaps on histological examination. In addition, cardiomyocytes showed degenerative defects in ventricular myocardial cells on ultrastructural analysis. Myofibril thinning and degenerative mitochondrial changes affected intercalated discs with fascia adherent, desmosomes, and gap junction. Intermittent short-duration re-oxygenation improve cardiac histological, ultrastructural and oxidant/antioxidant parameters changes during hypoxia.Conclusion: Hypoxia showed a substantial impact on myocardial architecture, as well as increased oxidative stress and pro-inflammatory cytokines. Intermittent short-duration re-oxygenation significantly decreases hypoxia-induced cardiac changes.

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Intermittent short‐duration reoxygenation protects against simulated high altitude‐induced pulmonary hypertension in rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 7 publications

References 47 publications

Positive end-expiratory pressure and risk of postoperative pulmonary complications in patients living at high altitudes and undergoing surgery at low altitudes: a single-centre, retrospective observational study in China

Positive end-expiratory pressure and risk of postoperative pulmonary complications in patients living at high altitudes and undergoing surgery at low altitudes: a single-centre, retrospective observational study in China

Protective effect of a chronic hypobaric hypoxic environment at high altitude on cardiotoxicity induced by doxorubicin in rats: a 7 T magnetic resonance study

Intermittent Short-Duration Re-oxygenation Attenuates Cardiac Changes in Response to Hypoxia: Histological, Ultrastructural and Oxidant/Antioxidant Parameters

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