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.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia.

BACKGROUND: Altitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m. METHODS: The incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge. RESULTS: There was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year. CONCLUSIONS: At altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe. TRIAL REGISTRATION: The study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

Challenges in the management of high-altitude illnesses and emergencies in Bhutan and Nepal.

Many popular tourist attractions and trekking routes in Bhutan and Nepal are situated between 3000 and 6000 m in elevation. High-altitude emergencies are becoming more common and medical providers must be aware of the practical and medical issues in managing these disorders. We reflect on the challenges in providing high-altitude emergency medical services in Bhutan and Nepal.

Endotracheal Intubation at 3,600 Meters Above Sea Level for High-Altitude Pulmonary Edema Followed by Helicopter Evacuation in Nepal.

Ranging from 64 to 8848 m above sea level, Nepal is a country rich in hilly and mountainous terrain.1 24.8% of Nepal's land area is above 3000 m, 18.9% is between 3000 and 5000 m, and 5.9% is above 5000 m.2 Hikers and trekkers are increasingly attracted to this challenging altitude and terrain, which presents risks for altitude sickness and other physical complications. Responding to medical emergencies in high-altitude areas in Nepal is highly challenging. This difficulty is often exacerbated by inclement weather, unavailability of helicopters, and poor communication regarding the location and condition of patients requiring medical attention and evacuation. High-altitude pulmonary edema (HAPE) is an illness characterized by non-cardiogenic pulmonary edema, which occurs not infrequently in individuals who rapidly ascend above 2500-3000 m in elevation,3 and which has a high mortality rate if not treated in a timely manner. Improved outcomes would be likely if skilled and equipped medical staff had better access to the sites of high-altitude expeditions in Nepal, so that life-saving interventions could be performed promptly. We report the case of a patient with HAPE who was intubated in the field at an altitude of 3600 m, and then evacuated via helicopter to a healthcare facility.

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

BACKGROUND: 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. METHODS: We compare the effect of these two different therapies on oxygen saturation measured by pulse oximetry (SpO2) over time. RESULT: 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. CONCLUSIONS: 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.

Companion Rescue and Risk Management of Trekkers on the Everest Trek, Solo Khumbu Region, Nepal.

BACKGROUND: Trekking to high-altitude locations presents inherent health-related hazards, many of which can managed with specific first aid (FA) training. This study evaluates the trip preparation, FA knowledge, and FA self-assessment of trekkers (organized by tour operators vs. individually planned tours). Data obtained shall be used for specific FA trip preparation and management of emergencies en route for this population. METHODS: A total of 366 trekkers on the Everest Base Camp Trek, Nepal, were interviewed using a questionnaire specifically designed to evaluate their FA knowledge and management of emergencies. Data evaluation was performed using descriptive statistics. RESULTS: A total of 40.5% of trekkers experienced at least one medical incident during their trip, of which almost 50% were due to acute mountain sickness (AMS). There was more AMS in commercially organized groups than in individually planned ones (55% vs. 40%). For more than 50%, no medical care was available during their trip. A total of 80% could answer only 3/21 FA questions completely correctly. Only 1% showed adequate knowledge concerning FA strategies. A total of 70% were willing to enroll in an FA class specialized towards the needs of trekkers. CONCLUSIONS: The importance of high-altitude FA knowledge and trip preparation is widely underestimated. There is an unmet demand amongst trekkers for specific wilderness FA classes.

Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity.

STUDY OBJECTIVES: Chronic mountain sickness (CMS) is commonly observed among Andean and other highland populations. Sleep-disordered breathing (SDB) is highly prevalent at high altitude, and SDB and nocturnal hypoxemia have been observed in CMS. Phlebotomy is commonly performed to treat CMS, but it is unknown whether reducing hematocrit improves SDB. We hypothesized that isovolemic hemodilution (IVHD) in CMS would reduce SBD severity and improve sleep efficiency. METHODS: Six participants with CMS and 8 without CMS, all residents of Cerro de Pasco, Peru (altitude 4340 m), completed baseline nocturnal sleep studies. CMS participants then underwent IVHD, and nocturnal sleep studies were repeated 24-48 hours after IVHD. We analyzed sleep apnea severity, nocturnal oxygenation, and sleep quality in those with CMS relative to those without CMS, and the effects of IVHD in CMS participants. RESULTS: Participants with CMS did not have altered sleep architecture, sleep apnea severity, or nocturnal oxygenation relative to non-CMS participants. However, IVHD in CMS increased apnea-hypopnea index (40.9 ± 6.9 events/h to 61.5 ± 7.7 events/h, P = .009). IVHD increased oxyhemoglobin desaturation index (P = .008) and the percentage of sleep time spent with oxyhemoglobin saturation at or below 80% (P = .012). There was no effect of IVHD on sleep efficiency, arousal index, or sleep staging. CONCLUSIONS: In this cohort, CMS was not associated with worsened SDB or changes in sleep architecture. IVHD, a putative therapeutic option for participants with CMS, appears to worsen nocturnal oxygenation and SDB within 48 hours post-IVHD. CITATION: Sanchez-Azofra A, Villafuerte FC, DeYoung PN, et al. Isovolemic hemodilution in chronic mountain sickness acutely worsens nocturnal oxygenation and sleep apnea severity. J Clin Sleep Med. 2022;18(10):2423-2432.

Clinician's Corner: Counseling Patients with Pulmonary Vascular Disease Traveling to High Altitude.

Ulrich, Silvia, Mona Lichtblau, Simon R. Schneider, Stéphanie Saxer, and Konrad E. Bloch, Clinician's corner: counseling patients with pulmonary vascular disease traveling to high altitude. High Alt Med Biol. 23:201-208, 2022.-Pulmonary vascular diseases (PVDs) with precapillary pulmonary hypertension (PH), such as pulmonary arterial or chronic thromboembolic PH, impair exercise performance and survival in patients. Vasodilators and other treatments improve quality of life and prognosis to an extent in patients who have PVDs as chronic disorders. Obviously, patients with PVD wish to participate in usual daily activities, including travel to popular settlements and mountainous regions located at high altitude. However, the pulmonary hemodynamic impairment due to PVD leads to blood and tissue hypoxia, particularly during exercise and sleep. It is thus of concern that alveolar hypoxia at higher altitude may exacerbate patients' symptoms and lead to decompensation. Current PH guidelines discourage high-altitude exposure for fear of altitude-related adverse health effects. However, several recent well-designed prospective and randomized trials show that despite altitude-induced hypoxemia, pulmonary hemodynamic changes and impairment of exercise performance in patients with PVD are similar to the responses in healthy people or in patients with mild chronic obstructive pulmonary disease. The vast majority of patients with PVD can tolerate short-term exposure to moderate altitudes up to 2,500 m. For the roughly 10% of patients with stable disease who develop severe hypoxemia when ascending to 2,500 m, they respond well to low-level supplemental oxygen support. The best low-altitude predictors for adverse health effects at high altitude are the known clinical risk factors for PVD such as symptoms, functional class, exercise capacity, and exertional oxygen desaturation, whereas hypoxia altitude simulation testing is of little additive value. In any case, patients should be instructed that altitude-related adverse health effects may be difficult to predict and that in case of worsening symptoms, immediate accompanied descent to lower altitude and oxygen therapy are required. Patients with severe hypoxemia near sea level may safely visit high-altitude regions up to 1,500-2,000 m while continuing oxygen therapy and avoiding strenuous exercise. All PH patients should be counseled before any high-altitude sojourn by doctors with experience in PVD and high-altitude medicine and have an action plan for the occurrence of severe hypoxemia and other altitude-related conditions such as acute mountain sickness.

Accessory Climbing Routes Associated With More Rescue Operations Than the Main Climbing Route: A Retrospective 12-Year Report of Yushan National Park.

INTRODUCTION: This study compared the casualties and types of rescues conducted on the main climbing route (MCR) and accessory climbing routes (ACRs) in Yushan National Park (YSNP) between 2008 and 2019. METHODS: We collected the following information for all documented mountain rescue operations conducted on the MCRs and ACRs in YSNP between 2008 and 2019: accident location, casualty type, victim number, and type of rescue. The victims were categorized as to injury, illness, mortality, or no medical problem (NMP) groups according to their condition at the time of rescue. RESULTS: Two-hundred forty-four rescue operations involving 329 victims were conducted during the 12-y study period. Among them, 105 (32%) did not require medical treatment, 102 (31%) were injured, 82 (25%) were ill, and 40 (12%) were deceased. Of the 82 individuals with illness, 69 (84%) had acute altitude sickness. The accident and mortality rates on the ACRs were significantly higher than those on the MCR (P<0.001; χ2). The ACR incidents involved significantly higher percentages of helicopter-based rescues and victims in the NMP group (P<0.001). CONCLUSIONS: Acute altitude sickness accounted for most of the rescues. ACRs had higher injury and mortality rates and required more helicopter-based rescues for patients who did not have medical problems. This study may serve as a reference to reduce casualties and overuse of helicopters by educating tourists on the appropriate use of maps and the evaluation of trails in relation to weather conditions.

Respiratory physiology at high altitude and considerations for pediatric patients.

Over 150 million people, including many children, live at high altitude (>2500 m) with the majority residing in Asia and South America. With increases in elevation, the partial pressure of oxygen (pO2) is reduced, resulting in a hypobaric hypoxic environment. Fortunately, humans have evolved adaptive processes which serve to acclimate the body to such conditions. These mechanisms, occurring along a specific time course, result in tachypnea, tachycardia, diuresis, and hematopoiesis, and a shift in the oxygen dissociation curve favoring an increased affinity for oxygen. These, along with other physiological effects, including increased pulmonary vascular resistance, alterations in cerebral blood flow, and changes in sensitivity to opioids, must be considered when administering anesthesia at high altitudes. Susceptible individuals or those who ascend too quickly may outpace the body's ability to acclimate resulting in one or more forms of high-altitude sickness ranging from the milder acute mountain sickness to the more serious conditions of high-altitude pulmonary edema and cerebral edema, either of which can be life-threatening if not promptly recognized and treated. Since the adaptive mechanisms for acclimatization greatly affect the cardiopulmonary systems, patients with underlying health issues such as sleep apnea, congenital heart disease, and asthma may have susceptibilities and warrant special consideration. Clinicians should have an understanding of the physiologic adaptations, anesthetic considerations, and special concerns in these populations in order to offer the best care possible.

High-altitude mountain telemedicine.

INTRODUCTION: An innovative teleconsultation platform has been designed, developed and validated between summer 2017 and winter 2018, in five mountain huts and in three remote outpatient clinical centres of the Italian region Valle d'Aosta of the Mont Blanc massif area. METHODS: An ad-hoc videoconference system was developed within the framework of the e-Rés@MONT (Interreg ALCOTRA) European project, to tackle general health problems and high-altitude diseases (such as acute mountain sickness, high-altitude pulmonary and cerebral oedema). The system allows for contacting physicians at the main hospital in Aosta to perform a specific diagnosis and to give specific advice and therapy to the patients in an extreme environment out-hospital setting. At an altitude between 1500-3500 m, five trained nurses performed clinical evaluations (anamnesis, blood pressure, heart rate, oxygen saturation), electrocardiographic and echography monitoring on both tourists and residents as necessary; all of the collected data were sent to the physicians in Aosta. RESULTS: A total of 702 teleconsultation cases were performed: 333 dismissed (47%), 356 observed (51%) and 13 immediate interventions (2%). In 30 cases the physicians decided there was no need for helicopter and ambulance rescue intervention and hospital admissions. The main physiological measures, the classified pathologies, the severe cases and the cost savings are described in this article. DISCUSSION: The e-Rés@MONT teleconsultation platform has been discussed in terms of treated cases, feasibility, proactivity in reducing complexities, direct and indirect advantages, and diagnostics help; moreover, general and specific pros and cons have been debated, and future steps have been exposed.

Mal de montaña de tipo agudo, subagudo y crónico / Acute, subacute and chronic mountain sickness

Más de 100 millones de personas ascienden cada año a áreas montañosas elevadas en todo el planeta y en altitudes no extremas (< 5.500 m) entre el 10 y el 85% se ven afectados por el denominado mal agudo de montaña, la enfermedad más frecuentemente inducida por una hipoxia hipobárica ligera-moderada. Asimismo, unos 140 millones de seres humanos viven de forma permanente en cotas comprendidas entre 2.500-5.500 m y hasta un 10% de ellos padecen la forma subaguda del mal de montaña (hipertensión pulmonar de la gran altitud) o la forma crónica (enfermedad de Monge), esta última especialmente frecuente en etnias andinas. La presente revisión expone los conceptos generales más relevantes en torno a estas 3variantes clínicas, las cuales pueden ser incapacitantes, llegar a complicarse y ser potencialmente mortales, siendo esencial realizar una correcta prevención, diagnóstico, terapéutica y manejo de las mismas en un entorno hostil como es la alta montaña (AU)

More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500 m), 10–85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500–5500 m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential (AU)

Acute, subacute and chronic mountain sickness.

More than 100 million people ascend to high mountainous areas worldwide every year. At nonextreme altitudes (<5500m), 10-85% of these individuals are affected by acute mountain sickness, the most common disease induced by mild-moderate hypobaric hypoxia. Approximately 140 million individuals live permanently at heights of 2500-5500m, and up to 10% of them are affected by the subacute form of mountain sickness (high-altitude pulmonary hypertension) or the chronic form (Monge's disease), the latter of which is especially common in Andean ethnicities. This review presents the most relevant general concepts of these 3 clinical variants, which can be incapacitating and can result in complications and become life-threatening. Proper prevention, diagnosis, treatment and management of these conditions in a hostile environment such as high mountains are therefore essential.

Oxygen Enrichment Mitigates High-Altitude Hypoxia-Induced Hippocampal Neurodegeneration and Memory Dysfunction Associated with Attenuated Tau Phosphorylation.

Cai, Jing, Junyong Ruan, Xi Shao, Yuanjun Ding, Kangning Xie, Chi Tang, Zedong Yan, Erping Luo, and Da Jing. Oxygen enrichment mitigates high-altitude hypoxia-induced hippocampal neurodegeneration and memory dysfunction associated with attenuated tau phosphorylation. High Alt Med Biol. 22:274-284, 2021. Background: Brain is predominantly vulnerable to high-altitude hypoxia (HAH), resulting in neurodegeneration and cognitive impairment. The technology of oxygen enrichment has proven effective to decrease the heart rate and improve the arterial oxygen saturation by reducing the equivalent altitude. However, the efficacy of oxygen enrichment on HAH-induced cognitive impairments remains controversial based on the results of neuropsychological tests, and its role in HAH-induced hippocampal morphological and molecular changes remains unknown. Therefore, this study aims to systematically investigate the effects of oxygen enrichment on the memory dysfunction and hippocampal neurodegeneration caused by HAH. Materials and Methods: Fifty-one male Sprague-Dawley rats were equally assigned to three groups: normal control, HAH, and HAH with oxygen enrichment (HAHO). Rats in the HAH and HAHO groups were exposed to hypoxia for 3 days in a hypobaric hypoxia chamber at a simulated altitude of 6,000 m. Rats in the HAHO group were supplemented with oxygen-enriched air, with 12 hours/day in the hypobaric hypoxia chamber. Results: Our results showed that oxygen enrichment improved the locomotor activity of HAH-exposed rats. The Morris water maze test revealed that oxygen enrichment significantly ameliorated HAH-induced spatial memory deficits. Oxygen enrichment also improved morphological alterations of pyramidal cells and the ultrastructure of neurons in the hippocampal CA1 region in rats exposed to acute HAH. Tau hyperphosphorylation at Ser396, Ser262, Thr231, and Thr181 was also significantly attenuated by oxygen enrichment in HAH-exposed rats. Conclusions: Together, our study reveals that oxygen enrichment can ameliorate HAH-induced cognitive impairments associated with improved hippocampal morphology and molecular expression, and highlights that oxygen enrichment may become a promising alternative treatment against neurodegeneration for humans ascending to the plateau.

Diploma in Mountain Medicine: A Perspective of a Female Doctor from Nepal.

Poudel, Sangeeta. Diploma in mountain medicine: a perspective of a female doctor from Nepal. High Alt Med Biol. 22:417-419, 2021.-Mountaineering is an alluring recreation receiving increasing global attention. With increasing adventure activities in the mountain, the risk of mishaps is high. Each year many trekkers, athletes, pilgrims, and porters are significantly affected and some even lose their lives due to a lack of knowledge in identification and management of altitude illness and other traumatic injuries. The diploma in mountain medicine (DiMM) trains participants in high-altitude environments to access area safety, diagnose, treat, and evacuate victims using available resources, improvised techniques, and rope skills. Doctors willing to work in the wilderness have to work in austere medical clinics, participate in search and rescues, volunteer at sporting events, or work on an expedition often being the only available doctor. Despite challenges, mountain doctors work in the wilderness as a hobby and some make a career of it, as in certain countries mountain medicine is now recognized as a subspeciality. As it becomes more accessible, the mountain medicine course is becoming increasingly popular, with the course in Nepal being no exception. It is developed as a specialty in developed countries, whereas in developing countries it will soon reach maturity. This is a personal report of a young female doctor taking part in a DiMM course in 2019 from Nepal.

[Blood pressure and high altitude: physiological response and clinical management]. / Presión arterial y altitud: respuestas fisiológicas y manejo clínico.

High altitude is an extreme environment that challenges human beings exposed because of work, recreational activities, or habitat. Exposure to hypobaric hypoxia results in physiological adaptations in response to the geography and the associated extreme environmental conditions. These acclimatization responses can be diverse and result from evolutionary changes and comorbidities. In this context, this review aims to identify the available evidence on the effects of high altitude on blood pressurefrom the physiological to clinical aspects at rest and during exerciseand the underlying mechanisms and possible clinical implications of acute and chronic intermittent hypoxia.

La gran altitud es un ambiente extremo que impone fuertes desafíos para el ser humano que se expone por actividades laborales, recreativas o que vive en esta condición. La exposición a hipoxia hipobárica genera una serie de adaptaciones fisiológicas dadas por el entorno geográfico y las condiciones ambientales extremas asociadas. Estas respuestas de aclimatación pueden ser heterogéneas, siendo el resultado de cambios evolutivos y de la existencia de comorbilidades o patologías asociadas. En este contexto, el objetivo de este artículo es identificar la evidencia científica acerca de los efectos de la altitud geográfica en la presión arterial, desde los aspectos fisiológicos a las implicaciones clínicas en reposo y ejercicio. Asimismo, se abordan los mecanismos subyacentes y las posibles implicaciones clínicas en hipoxia aguda e hipoxia intermitente crónica.

Effect of exercise training in rats exposed to chronic hypoxia: Application for Monge's disease.

Physical exercise may improve hematological conditions in high altitude dwellers suffering from Chronic Mountain Sickness (CMS), in reducing hemoglobin concentration. Therefore, the present study aimed to characterize the effects of 1-month exercise training session in a model of rats exposed to chronic hypoxia. Four groups of male rats were studied: normoxic sedentary (NS, n = 8), normoxic training (NT, n = 8), hypoxic sedentary (HS, n = 8), and hypoxic training group (HT, n = 8). Hypoxic groups were exposed to hypobaric hypoxia for one month (PB =433 Torr). Training intensity was progressively increased from a running speed of 10.4 to 17.8 m/min. Chronic hypoxia led to an increase in hematocrit (HCT) associated with a decrease in plasma volume despite an increase in water intake. Training led to a reduction in HCT (p < 0.01), with a non-significant increase in plasma volume and weight gain. Hypoxia and training had inhibitory effects on haptoglobin (NS group: 379 ± 92; HT: 239 ± 34 µg/ml, p < 0.01). Chronic hypoxia and exercise training increased SpO2 measured after acute hypoxic exposure. Training blunted the decrease in V˙ O2 peak, time of exhaustion, and maximum speed associated with chronic exposure to hypoxia. Chronic hypoxia led to a right ventricular hypertrophy, which was not corrected by 1-month exercise training. Altogether, by decreasing hematocrit, reducing body weight, and limiting performance decrease, training in hypoxia may have a beneficial effect on excessive erythropoiesis in chronic hypoxia. Therefore, regular exercise training might be beneficial to avoid worsening of CMS symptoms in high altitude dwellers and to improve their quality of life.

Markers of cardiovascular risk and their reversibility with acute oxygen therapy in Kyrgyz highlanders with high altitude pulmonary hypertension.

BACKGROUND: High altitude pulmonary hypertension (HAPH), a chronic altitude related illness, is associated with hypoxemia, dyspnea and reduced exercise performance. We evaluated ECG and pulse wave-derived markers of cardiovascular risk in highlanders with HAPH (HAPH+) in comparison to healthy highlanders (HH) and lowlanders (LL) and the effects of hyperoxia. METHODS: We studied 34 HAPH+ and 54 HH at Aksay (3250m), and 34 LL at Bishkek (760m), Kyrgyzstan. Mean pulmonary artery pressure by echocardiography was mean±SD 34±3, 22±5, 16±4mmHg, respectively (p<0.05 all comparisons). During quiet rest, breathing room air or oxygen in randomized order, we measured heart-rate adjusted QT interval (QTc), an ECG-derived marker of increased cardiovascular mortality, and arterial stiffness index (SI), a marker of cardiovascular disease derived from pulse oximetry plethysmograms. RESULTS: Pulse oximetry in HAPH+, HH and LL was, mean±SD, 88±4, 92±2 and 95±2%, respectively (p<0.05 vs HAPH+, both comparisons). QTc in HAPH+, HH and LL was 422±24, 405±27, 400±28ms (p<0.05 HAPH+ vs. others); corresponding SI was 10.5±1.9, 8.4±2.6, 8.5±2.0m/s, heart rate was 75±8, 68±8, 70±10 bpm (p<0.05, corresponding comparisons HAPH+ vs. others). In regression analysis, HAPH+ was an independent predictor of increased QTc and SI when controlled for several confounders. Oxygen breathing increased SI in HH but not in HAPH+, and reduced QTc in all groups. CONCLUSIONS: Our data suggest that HAPH+ but not HH may be at increased risk of cardiovascular mortality and morbidity compared to LL. The lack of a further increase of the elevated SI during hyperoxia in HAPH+ may indicate dysfunctional control of vascular tone and/or remodelling.