Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure

Purpose: The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent. VEGF level changes with dexamethasone, a commonly used AMS medication, may provide additional insight into AMS.Methods: Twelve healthy volunteers ascended Mt Fuji (3,700 m) and blood samples were obtained at distinct altitudes for VEGF analysis. Oxygen saturation (SPO2) measurements were also documented at the same time-point. Six out of the 12 study participants were prescribed dexamethasone for a second ascent performed 48 h later, and blood was again collected to establish VEGF levels.Results: Four key VEGF observations could be made based on the data collected: (i) the baseline VEGF levels between the two ascents trended upwards; (ii) those deemed to have AMS in the first ascent had increased VEGF levels (23.8–30.3 pg/ml), which decreased otherwise (23.8–30.3 pg/ml); (iii) first ascent AMS participants had higher VEGF level variability for the second ascent, and similar to those not treated with dexamethasone; and (iv) for the second ascent dexamethasone participants had similar VEGF levels to non-AMS first ascent participants, and the variability was lower than for first ascent AMS and non-dexamethasone participants. SPO2 changes were unremarkable, other than reducing by around 5% irrespective of whether measurement was taken for the first or second ascent.Conclusion: First ascent findings suggest a hallmark of AMS could be elevated VEGF levels. The lack of an exercise-induced VEGF level change strengthened the notion that elevated plasma VEGF was brain-derived, and related to AMS.

Effect of intermittent normobaric hypoxia exposure on acclimatization to high altitude by air induction

Background: In emergency like condition, defence personnel are deployed to high altitude without proper acclimatization. Maladaption at high altitude leads to high altitude illness like acute mountain sickness (AMS), high altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE) which hampers the operational capabilities. Aims and Objectives: The aim of the present study was to assess the effect of intermittent normobaric hypoxia exposure (IHE) at sea level on different physiological responses during initial days of acclimatization at 3500m and 4000m altitudes in acute induction. Materials and Methods: The IHE subjects were exposed to 12% FIO2 (equivalent altitude 14500 ft) for 4 hrs/day for 4 consecutive days at sea level and 5th day they were inducted by air to 3500m altitude. Baseline recording of different physiological parameters like cardiovascular, respiratory, oxygen saturation and AMS score were measured at sea level as well as 3500m altitude on daily basis for 6 days to assess acclimatization status. To confirm acclimatization status at 3500m, on fifth day the IHE group subjects were transported by road to 4000m and again measured different basal physiological parameters (like cardiovascular, oxygen saturation and AMS score) for four consecutive days. Results: Different physiological parameters of IHE treated group were stabilized by day 4 of air induction at 3500m altitude. Whereas, at 4000m altitude, these parameters were stabilized by day 2 of induction. Conclusion: Acclimatization schedules of four days at 3500m and two days at 4000m are essential to avoid malacclimatization/or high-altitude illness.

Rapid Acclimatisation to High Altitude by Intermittent Hypoxia Training at Sea Level Role of Biochemical Markers

Rapid induction of soldiers to high altitude under emergency situation may lead to higher incidence of acute mountain sickness (AMS) and other high altitude illness. Intermittent Hypoxia Training (IHT) at sea level before going to high altitude is an approach for rapid acclimatisation. This approach may be helpful to reduce the occurrence of AMS and leads to better acclimatisation at high altitude in shorter duration. The present study evaluates the role of biochemical markers of acclimatisation after IHT before induction to actual high altitude. The study participants were Indian Army Personnel (n=30) and they were divided into two groups of control (n=16) and IHT exposed (n=14). The intermittent hypoxia training was administered at 12 per cent Oxygen for 4h/day for 4 days at sea level using normobaric hypoxia chamber and within 24 hrs - 48 hrs the subjects were airlifted to Leh, Ladakh, India at 11,700 ft. Preconditioning with IHT may be beneficial in maintaining antioxidant levels and ameliorate oxidative stress at high altitude. The hypoxia responsive proteins like Hemeoxygenase -1 (HO-1) and Vascular endothelial growth factor (VEGF) and the cytoprotective stress proteins, which facilitate the acclimatisation, may also get benefited by IHT exposure.

Qi-Long-Tian formula extract alleviates symptoms of acute high-altitude diseases via suppressing the inflammation responses in rat

Background Chinese Yunnan Province, located in the Yunnan–Guizhou Plateau, is a famous tourist paradise where acute high-altitude illness common occurs among lowland people visitors due to non-acclimatization to the acute hypobaric hypoxia (AHH) conditions. Traditional Chinese medicine, such as Qi-Long-Tian (QLT) formula, has shown effectiveness and safety in the treatment of acute high-altitude diseases. The aim of this study was to clarify the therapeutic mechanisms of this traditional formula using a rat model in a simulated plateau environment. Methods Following testing, lung tissue samples were evaluated by hematoxylin–eosin staining and for biochemical characteristics. mRNA-Seq was used to compare differentially expressed genes in control rats, and in rats exposed to AHH and AHH with QLT treatment. Results Inflammation-related effectors induced following QLT treatment for AHH included MMP9 and TIMP1, and involved several phosphorylation signaling pathways implicated in AHH pathogenesis such as PI3K/AKT and MAPK signaling. Conclusion This study provides insights into the major signaling pathways induced by AHH and in the protective mechanisms involved in QLT formula activity.

Pericytes within a pulmonary neurovascular unit in coronavirus disease 2019-elicited pathological changes

: A pericyte-centered theory suggesting that embolisms occurring within the microvasculature of a neurovascular unit can result in either parenchymal hemorrhage or intravascular congestion is presented here. Dysfunctional microvascular pericytes are characterized by their location in the neurovascular unit, either on the arteriole or venule side. Pathophysiological and pathological changes caused by coronavirus disease 2019 (COVID-19) include pulmonary hypertension, edema, focal hemorrhage, microvascular congestion, and thrombosis. In this paper, I have extended the application of the pericytes-centered hypothesis to COVID-19 by proposing the concept of a pulmonary neurovascular unit (pNVU); application of this concept implies that human lungs contain approximately 300 million pNVUs. This concept of existing local regulation of microvascular blood flow is supported by the observation of pathophysiology in pulmonary embolism and in acute high-altitude illness. The autonomic control seen in these three disease states matches blood flow with oxygen supply in each pNVU to maintain physiological blood oxygen saturation level. Here, I illustrate how the malfunction of microvascular pericytes may cause focal hemorrhage, edema or microvascular congestion and thrombosis. A bypass existing in each pNVU would autonomically deviate blood flow from a COVID-19-affected pNVU to other healthy pNVUs. This action would prevent systemically applied medicines from reaching the therapeutic threshold in COVID-19- affected pNVUs. While testing this hypothesis with experimental evidence is urgently needed, supporting therapy aimed at improving microcirculation or rebuilding the physiological function of microvascular pericytes is recommended as a potentially effective treatment of COVID 19.

Abstract 14228: Pericytes Within a Pulmonary Neurovascular Unit in Covid-19-elicited Pathologic Changes

A pericyte-centered hypothesis suggests that embolisms occurring within microvasculature of a neurovascular unit can result in either parenchymal hemorrhage or intravascular congestion. Dysfunctional microvascular pericytes are featured depending on their location in the neurovascular unit. I extend the hypothesis by proposing a concept of pulmonary neurovascular unit (pNVU). In simulating pathophysiology in pulmonary embolisms, acute high-altitude illness and COVID-19, an existing local regulation of microvascular blood flow is believable. This control balances blood flow with oxygen supply to maintain physiological blood oxygen saturation level. We have reported a working module for the neurovascular unit in the sexually dimorphic nucleus of the preoptic area. Pericytes, labeled with alpha-smooth muscle actin immunoreactivity, are significantly denser within the microvasculature of the neurovascular unit in males, signifying their biological functions or potential pathophysiological role in diseases. Noticeably, an illustration provides an explanation of how malfunction of microvascular pericytes causes pulmonary focal hemorrhage, edema or microvascular congestion and thrombi [Fig. 1]. A bypass existing in the pNVU would autonomically deviate blood flow from COVID-19-affected pNVU to other healthy pNVU. Consequentially, systematically applied medicines including chloroquine and/or hydroxychloroquine became valueless due to low concentration of the medicine in the COVID-19-affected regions. Alternatively, a preventive, early antiviral therapy may be efficacious because dysfunctional blood-air exchange precedents and malfunction of pulmonary microcirculation follows. While testing the hypothesis with experimental evidence is urgently needed, supporting therapy aimed at improvement of microcirculation or rebuilding of microvascular pericytes’ physiological function may be recommended during the COVID pandemic.

High Altitude Illness

Key Points Individuals traveling to high altitudes (usually to ≥2,500 m) are at risk of developing high altitude illness (HAI), especially if ascending quickly.Acclimatization and slow ascent are the most effective ways to avoid HAI.Acetazolamide is prevention and treatment.High altitude illnesses typically respond to descent, oxygen therapy, or both.