Treatment Of High Altitude Pulmonary Edema Research Articles

Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish theHAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through thetail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Effect of furosemide in the treatment of high-altitude pulmonary edema

BackgroundHigh-altitude pulmonary edema (HAPE) refers to the onset of breathlessness, cough, and fever at rest after arriving at high altitudes. It is a life-threatening illness caused by rapid ascent to high altitudes. Furosemide is controversial in HAPE treatment but is routinely used in China. Further research is needed to assess its efficacy and impact on HAPE management and prognosis. The aim of this study is to determine the effectiveness of furosemide for HAPE.MethodsA retrospective was conducted to analysis of patients with HAPE admitted to the People’s Hospital of Shigatse City from January 2018 to September 2023. Patients were divided into furosemide group and non-furosemide group for further analysis. Clinical variables including demographic information, comorbidities, vital signs, inflammatory markers, biochemical analysis, CT severity score and prognostic indicators were collected.ResultsA total of 273 patients were enrolled, with 209 patients in the furosemide group and 64 patients in the non-furosemide group. The furosemide group showed a significantly decrease in CT severity scores compared to the non-furosemide group. Subgroup analysis showed that the longer the duration of furosemide use, the more pronounced the improvement in lung CT severity scores. But there were no significant differences in length of hospital stay and in-hospital mortality between the two groups.ConclusionFurosemide helps alleviate pulmonary edema in HAPE patients, but further research is needed to clarify its impact on prognosis.

Continuous Positive Airway Pressure in the Treatment of Pediatric High Altitude Pulmonary Edema: A Case Study.

Treatment of high altitude pulmonary edema (HAPE) can be challenging and is further complicated in the pediatric patient in the prehospital environment. The following case presents a decompensating pediatric patient with HAPE in the prehospital aeromedical environment. It illustrates the potential benefit of continuous positive airway pressure (CPAP) as a treatment modality in the treatment of HAPE.

Whole transcriptome landscape in HAPE under the stress of environment at high altitudes: new insights into the mechanisms of hypobaric hypoxia tolerance.

High altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood. We conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential. We observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 'A3SS' events, 103 'A5SS' events, 545 'MXE' events, 14 'RI' events, and 1,482 'SE' events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ_0058497, hsa_circ_0081006, and hsa_circ_0083220 demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses. This study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE.

Initial Treatment of High-Altitude Pulmonary Edema: Comparison of Oxygen and Auto-PEEP

Improvement of oxygenation is the aim in the therapy of high-altitude pulmonary edema (HAPE). However, descent is often difficult and hyperbaric chambers, as well as bottled oxygen, are often not available. We compare Auto-PEEP (AP-Pat), a special kind of pursed lips breathing, against the application of bottled oxygen (O2-Pat) in two patients suffering from HAPE. We compare the effect of these two different therapies on oxygen saturation measured by pulse oximetry (SpO2) over time. In both patients SpO2 increased significantly from 65-70% to 95%. Above 80% this increase was slower in AP-Pat compared with O2-Pat. Therapy started immediately in AP-Pat but was delayed in O2-Pat because of organizational and logistic reasons. The well-established therapies of HAPE are always the option of choice, if available, and should be started as soon as possible. The advantage of Auto-PEEP is its all-time availability. It improves SpO2 nearly as well as 3 L/min oxygen and furthermore has a positive effect on oxygenation lasting for approximately 120 min after stopping. Auto-PEEP treatment does not appear inferior to oxygen treatment, at least in this cross-case comparison. Its immediate application after diagnosis probably plays an important role here.

Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders.

Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

Novel drugs in the management of acute mountain sickness and high altitude pulmonary edema.

Dear editor We read with great interest the review article titled “Wilderness medicine at high altitude: recent developments in the field” by Shah et al.1 The authors have comprehensively summarized the recent advances in the field of high altitude medicine relevant to sports and travel medicine. However, Shah et al have described potential drugs for management of high-altitude illnesses, such as acute mountain sickness (AMS), high altitude cerebral edema, and high altitude pulmonary edema (HAPE) as one group under the section “Novel drug treatment for AMS”. The pathophysiologies of these two sets of diseases (AMS/high altitude cerebral edema as one and HAPE as another set) are different2 and hence it would have been nice to have had the novel drugs described separately to elucidate the therapeutic approach for the two different classes of diseases. Shah et al have highlighted the possible beneficial use of dietary nitrate supplementation (as a source of nitric oxide [NO]) in AMS, but drugs such as inhaled NO and prostaglandin (Iloprost) for HAPE deserve a mention in this list of potential therapeutic agents.3,4 Anand et al have suggested significant beneficial effects of inhaled NO in HAPE patients.3 Iloprost in combination with NO has been found to decrease pulmonary arterial pressures in HAPE-susceptible individuals.4 Although, the latest guidelines on prevention and treatment of HAPE by the Wilderness Medical Society do not include these drugs, this is probably due to the limited work done on these drugs under field conditions of high altitude. Shah et al have also emphasized on specific phosphodiesterase type 5 inhibitors as potential therapeutic agents for AMS and HAPE. However, an expert panel from the Wilderness Medical Society do not recommend the use of phosphodiesterase type 5 inhibitors for AMS, but the same can be used for prevention (recommendation grade: 1C) and treatment (recommendation grade: 2C) of HAPE.2

High Altitude Pulmonary Oedema

High altitude pulmonary oedema (HAPE) is an important and preventable cause of death at high altitudes. However, little is known about the global incidence of HAPE, in part because most...

Molecular docking study of tripeptides VPP and IPP inhibiting angiotensin I converting enzyme to alleviate high altitude pulmonary edema

High altitude pulmonary edema (HAPE) remains the major cause of death related to high altitude exposure with a high mortality in absence of emergency treatment. Due to the deprival of oxygen in higher altitudes, the blood vessels constricts and squeezes blood in the vessels. This makes pressure to go up which in turn forces blood into air pockets in lungs that can kill people with HAPE. Angiotensin Converting Enzyme (ACE) is found in lung capillaries. It catalyses conversion of angiotensin I to angiotensin II which is a potent vasoconstrictor and inactivates bradykinin which is a potent vasodilator thereby causing HAPE. Tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) act as ACE inhibitors, that reduce vasoconstriction and facilitate vasodilation, so that they can be used in the treatment of HAPE. Enzyme-inhibitor docking is performed between Angiotensin I Converting Enzyme ACE and two natural inhibitors, tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) using the Patchdock Software. The docking study provided a quantitative energetic measure (Atomic Contact Energy) of 262.56 and 147.73 for ACE inhibition by VPP and IPP respectively. This ensures that the tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are able to inhibit the activity of the ACE which in turn can induce decreased formation of Angiotensin II and decreased inactivation of bradykinin thereby it can alleviate HAPE. Key words: High altitude pulmonary edema (HAPE), angiotensin converting enzyme, Val-Pro-Pro, Ile-Pro-Pro, patchdock

Standardization of methods for early diagnosis and on-site treatment of high-altitude pulmonary edema.

High-altitude pulmonary edema (HAPE) is a life-threatening disease of high altitude that often affects nonacclimatized apparently healthy individuals who rapidly ascend to high altitude. Early detection, early diagnosis, and early treatment are essential to maintain the safety of people who ascend to high altitude, such as construction workers and tourists. In this paper, I discuss various methods and criteria that can be used for the early diagnosis and prediction of HAPE. I also discuss the preventive strategies and options for on-site treatment. My objective is to improve the understanding of HAPE and to highlight the need for prevention, early diagnosis, and early treatment of HAPE to improve the safety of individuals ascending to high altitude.

Prevention and Treatment of High-Altitude Pulmonary Edema

We distinguish two forms of high altitude illness, a cerebral form called acute mountain sickness and a pulmonary form called high-altitude pulmonary edema (HAPE). Individual susceptibility is the most important determinant for the occurrence of HAPE. The hallmark of HAPE is an excessively elevated pulmonary artery pressure (mean pressure 36-51 mm Hg), caused by an inhomogeneous hypoxic pulmonary vasoconstriction which leads to an elevated pulmonary capillary pressure and protein content as well as red blood cell-rich edema fluid. Furthermore, decreased fluid clearance from the alveoli may contribute to this noncardiogenic pulmonary edema. Immediate descent or supplemental oxygen and nifedipine or sildenafil are recommended until descent is possible. Susceptible individuals can prevent HAPE by slow ascent, average gain of altitude not exceeding 300 m/d above an altitude of 2500 m. If progressive high altitude acclimatization would not be possible, prophylaxis with nifedipine or tadalafil for long sojourns at high altitude or dexamethasone for a short stay of less then 5 days should be recommended.

Secondary Prevention of HAPE in a Mount Everest Summiteer

Climbers who have suffered a previous episode of high altitude pulmonary edema (HAPE) are at significantly increased risk of developing it again on return to high altitude. In spite of the high mortality associated with HAPE, some climbers are willing to take this risk in order to summit the tallest mountains in the world. This is a case report of a climber who suffered an episode of HAPE partway up Mount Everest. He was determined to complete his summit attempt that same climbing season, which would involve a return to extreme altitude less than 3 weeks following recovery. Based on experimental evidence suggesting that sildenafil, salmeterol, and acetazolamide may have therapeutic value for both the prevention and treatment of HAPE, he used these medications for secondary prevention. He was able to successfully reach the summit of Mount Everest and return to base camp without any evidence of recurrence of pulmonary edema. This provides clinical evidence that medication can be used to increase the safety margin for HAPE-susceptible individuals traveling to extremely high altitudes.

Pharmacotherapy of High-Altitude Illness

High-altitude illness (HAI) encompasses an array of conditions that may occur in individuals who travel to high elevations, including acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. Individuals with a history of HAI are predisposed to developing HAI; however, other risk factors are not well defined. The primary method of preventing HAI is acclimatization through gradual ascent to high altitude. In addition, many studies have assessed the use of pharmacologic prophylaxis. The most studied and widely recommended prophylactic agent is acetazolamide; additional agents that have been considered include dexamethasone, Gingko biloba, antioxidant vitamins, nifedipine, aspirin, and salmeterol. The treatment of choice for all forms of HAI is descent to lower altitude. The use of additional treatments, including supplemental oxygen, varies depending on the severity of the clinical presentation. Acetazolamide and dexamethasone have been studied as adjunctive treatments for acute mountain sickness, while nitric oxide and nifedipine have been evaluated for the treatment of high-altitude pulmonary edema. Data with analgesics and phosphodiesterase-5 inhibitors, while limited, are promising. This review will present the evidence supporting the use of pharmacotherapy for prevention and treatment of HAI.

Are sildenafil and theophylline effective in the prevention of high-altitude pulmonary edema?

High-altitude pulmonary edema reflects a potentially life-threatening condition affecting susceptible persons in the second night after ascent to altitudes above 2500 m. Currently, nifedipine is the only pharmacological intervention approved for both, prevention and treatment of high-altitude pulmonary edema. We evaluated the application of the phosphodiesterase-V inhibitor sildenafil combined with the non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In theory, the proposed regimen can impede the two main pathophysiological features of high-altitude pulmonary edema: the deleteriously high pulmonary artery pressure (sildenafil's task) on the one hand, and the activation of an inflammatory cascade (theophylline's task) on the other hand. We suggest that these orally applicable phosphodiesterase inhibitors might be useful in the prevention of high-altitude pulmonary edema.

Treatment of high-altitude pulmonary edema by bed rest and supplemental oxygen

We evaluated the safety and efficacy of treating high-altitude pulmonary edema (HAPE) by bed rest and supplemental oxygen at moderate altitudes. We also characterized clinical parameters in HAPE before and after treatment. Case series. Two primary care centers at about 9,200 feet (2,800 meters) above sea level. All patients aged 16-69 years who had been diagnosed with HAPE and were treated with bed rest and supplemental oxygen. Patients were seen on a follow-up visit. Selected patients were treated with bed rest and supplemental oxygen rather than hospital admission or descent. Patients were considered improved on follow-up if room air arterial oxygen saturation was increased by 10 percentage points or if their symptoms had improved. Of 58 patients with confirmed HAPE, 25 (43%) were treated by bed rest and supplemental oxygen and were seen on return visits to the clinic. All of the treated patients improved at the return visit. Systolic blood pressure, heart rate, respiratory rate, and temperature decreased significantly between the first visit and the return visit. Oxygen saturation improved between visits. Some patients with HAPE at moderate altitudes where medical facilities are available can be safely treated with bed rest and oxygen without descent.

Nifedipine does not prevent acute mountain sickness.

Nifedipine has been shown effective for prevention and treatment of high altitude pulmonary edema (HAPE). Because acute mountain sickness (AMS) and HAPE may share common pathophysiologic mechanisms, we evaluate the prophylactic effect of nifedipine on the development of AMS in 27 mountaineers not susceptible to HAPE. They were randomly assigned to receive in a double-blind manner either nifedipine or placebo during rapid ascent to 4559 m and a subsequent three-day sojourn at this altitude. Nine of 14 subjects on nifedipine and eight of 13 subjects on placebo felt ill at high altitude. Pulmonary artery pressures (PAP) estimated by Doppler echocardiography were significantly lower with nifedipine, but arterial PO2, oxygen saturation, and alveolar-arterial oxygen pressure gradient were not significantly different between groups at high altitude. This study demonstrates that lowering PAP has no beneficial effect on gas exchange and symptoms of AMS in subjects not susceptible to HAPE. Therefore, nifedipine cannot be recommended for prevention of AMS, and its use in high altitude medicine should be limited to prevention and treatment of HAPE.

Protocols for the use of a portable hyperbaric chamber for the treatment of high altitude disorders

Descent remains the definitive treatment for high altitude illness. However, in alpine settings of over 8000 ft, immediate evacuation is often impossible. A portable, lightweight (7 kg) hyperbaric bag has been devised capable of withstanding a pressure of 2 psi. The author investigated the optimal period of treatment in the bag to achieve resolution of symptoms and to prevent recurrence. Observations were recorded in Pheriche, Nepal at 13 920 ft. At this altitude, inflation of the bag to 2 psi effects a descent to 8400 ft. Dramatic improvements were seen in victims with symptoms of acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and cerebral edema (HACE). AMS, HAPE and HACE patients required time frames of 2, 4, and 6 h respectively to provide resolution of symptoms without complications or deterioration. The author advocates the hyperbaric bag as an effective adjunct and temporizing measure in the treatment of HAPE and HACE.

Letter: Furosemide for high altitude pulmonary edema.

To the Editor.— The recent reply to a question regarding first aid equipment and acclimatization in mountain climbing (232:657, 1975) merits comment. Dr Mason suggests that furosemide (Lasix) given in large doses orally and intravenously may have dramatic beneficial effect in the treatment of high altitude pulmonary edema (HAPE). A case is described in which 120 mg orally and 80 mg intravenously were given, resulting in a 4,000-ml diuresis in 6 1/2 hours, with allegedly beneficial results. Unfortunately, such anecdotal reports have led to the indiscriminate use of furosemide in the treatment of HAPE as well as for the prevention of mountain sickness. Recently, a climbing party leader requested information about giving furosemide to all members of his party to prevent mountain sickness! Dr Mason points out that drug prophylaxis has been disappointing. It should be pointed out that there is insufficient evidence from appropriately conducted clinical studies that furosemide