Left ventricular adaptation to high altitude: speckle tracking echocardiography in lowlanders, healthy highlanders and highlanders with chronic mountain sickness.
Dedobbeleer Chantal,Hadefi Alia,Pichon Aurelien,Villafuerte Francisco,Naeije Robert,Unger Philippe
The international journal of cardiovascular imaging
Hypoxic exposure depresses myocardial contractility in vitro, but has been associated with indices of increased cardiac performance in intact animals and in humans, possibly related to sympathetic nervous system activation. We explored left ventricular (LV) function using speckle tracking echocardiography and sympathetic tone by spectral analysis of heart rate variability (HRV) in recently acclimatized lowlanders versus adapted or maladapted highlanders at high altitude. Twenty-six recently acclimatized lowlanders, 14 healthy highlanders and 12 highlanders with chronic mountain sickness (CMS) were studied. Control measurements at sea level were also obtained in the lowlanders. Altitude exposure in the lowlanders was associated with slightly increased blood pressure, decreased LV volumes and decreased longitudinal strain with a trend to increased prevalence of post-systolic shortening (p = 0.06), whereas the low frequency/high frequency (LF/HF) ratio increased (1.62 ± 0.81 vs. 5.08 ± 4.13, p < 0.05) indicating sympathetic activation. Highlanders had a similarly raised LF/HF ratio, but no alteration in LV deformation. Highlanders with CMS had no change in LV deformation, no significant increase in LF/HF, but decreased global HRV still suggestive of increased sympathetic tone, and lower mitral E/A ratio compared to healthy highlanders. Short-term altitude exposure in lowlanders alters indices of LV systolic function and increases sympathetic nervous system tone. Life-long altitude exposure in highlanders is associated with similar sympathetic hyperactivity, but preserved parameters of LV function, whereas diastolic function may be altered in those with CMS. Altered LV systolic function in recently acclimatized lowlanders may be explained by combined effects of hypoxia and changes in loading conditions.
10.1007/s10554-015-0614-1
Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders.
Sydykov Akylbek,Mamazhakypov Argen,Maripov Abdirashit,Kosanovic Djuro,Weissmann Norbert,Ghofrani Hossein Ardeschir,Sarybaev Akpay Sh,Schermuly Ralph Theo
International journal of environmental research and public health
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.
10.3390/ijerph18041692
High altitude-induced borderline pulmonary hypertension impaired cardiorespiratory fitness in healthy young men.
Yang Te,Li Xiangjun,Qin Jun,Li Shuangfei,Yu Jie,Zhang Jihang,Yu Shiyong,Wu Xiaojing,Huang Lan
International journal of cardiology
OBJECTIVE:High altitude exposure has been suggested to cause borderline elevation of pulmonary artery pressure (PAP) in quite a few healthy individuals. This cohort study was to investigate the impact of altitude induced borderline pulmonary hypertension (PH) on cardiorespiratory fitness in healthy subjects. METHODS:299 healthy Chinese young men with normal PAP were consecutively studied between July 2011 and September 2013. Among these subjects 114 kept living at low altitude (450m), 91 ascended to high altitude (3700m) from low altitude within 24h (acute exposure), and 94 resided at 3700m for more than 1year (chronic exposure). Mean PAP and cardiac function were examined by echocardiography, and cardiorespiratory fitness was determined by predicted work capacity at a heart rate of 170beats per minute (PWC170). RESULTS:Mean PAP remained within normal range (<20mmHg) in 113 of 114 participants (99%) at low altitude. In contrast, the incidence of borderline PH (mPAP between 20 and 25mmHg) was 29% and 37% for respective acute and chronic exposures. Compared to the subjects with normal mPAP within each of the exposure groups, the subjects with borderline PH had increased right ventricular Tei index (RV-Tei), which correlated with the decline of PWC170 (acute exposure: r=-0.296, p=0.004; chronic exposure: r=-0.247, p=0.016). However, these changes were relatively milder than those with confirmed PH (mPAP>25mmHg). CONCLUSION:Borderline PH compromised cardiorespiratory fitness in healthy young men. The decline of cardiorespiratory fitness was related at least in part with the impaired right ventricular function, which was correlated with the elevated mPAP.
10.1016/j.ijcard.2014.12.044
Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage.
Wang Qingshu,Hu Ling,Hu Yu,Gong Gu,Tan Hua,Deng Li,Sun Xiaoqin,Yi Xiaobo,Sun Yangyang,Wu Wei,Li Tao
Cardiology
OBJECTIVE:To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage. METHODS:Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0.3 g Hb/kg/day or an equivalent volume of saline. The in vivo left ventricle function, cardiac enzyme release, histopathological changes, apoptosis and inflammation were also measured. RESULTS:High-altitude hypoxia induced significant cardiac damage, as demonstrated by impaired cardiac function and increased proapoptotic, proinflammatory and pro-oxidant markers. Pretreatment with CO-HBOC significantly improved cardiac performance, reduced cardiac enzyme release and limited myocardial apoptosis. The increased inflammatory response was also suppressed. In addition to the preserved mitochondrial structure, hypobaric hypoxia-induced mitochondrial oxidative damage was remarkably attenuated. Moreover, these antiapoptotic and antioxidative effects were accompanied by an upregulated phosphorylation of Akt, ERK and STAT3. CONCLUSION:This study demonstrated that CO-HBOC provides a promising protective effect on high-altitude hypoxia-induced myocardial injury, which is mediated by the inhibition of inflammation and mitochondrial oxidative damage.
10.1159/000448652
Metabolic Alterations of Qinghai-Tibet Plateau Pikas in Adaptation to High Altitude.
Cao Xue-Feng,Bai Zhen-Zhong,Ma Lan,Ma Shuang,Ge Ri-Li
High altitude medicine & biology
Cao, Xue-Feng, Zhen-Zhong Bai, Lan Ma, Shuang Ma, and Ri-Li Ge. Metabolic alterations of Qinghai-Tibet plateau pikas in adaptation to high altitude. High Alt Med Biol. 18:219-225, 2017.-To determine specific metabolic alterations in the myocardium of plateau pikas (Ochotona curzoniae) and potential metabolic biomarkers involved in their adaptation to the high-altitude environment of the Qinghai-Tibet Plateau. Ten pikas were captured by traps in the Kekexili Reserve (4630 m a.s.l; n = 5) and at the foot of the Laji Mountain (2600 m a.s.l; n = 5) on the Qinghai-Tibet Plateau, Qinghai Province, China. Metabolite levels were determined by gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) metabolomics, and multivariate statistical analysis was performed. Several metabolites involved in carbohydrate, fat, energy, and redox homeostasis pathways were significantly altered in pikas living at 4630 m. In addition, those pikas showed increased levels of lactic acid, sarcosine, 4-hydroxybutyrate, methionine, tartaric acid, ribose, tyrosine, pentadecanoic acid, 2-monoolein, 3,5-dihydroxyphenylglycine, trehalose-6-phosphate, succinic acid, myoinositol, fumaric acid, taurine, 2-hydroxybutanoic acid, gluconic acid, citrulline, and glutathione, but decreased levels of oleic acid and 2'-deoxyadenosine 5'-monophosphate. Metabolic activity is significantly altered in the myocardium of pikas in the high-altitude areas of the Qinghai-Tibet Plateau. This study provides important insights into metabolic biomarkers related to the adaptation of pikas to high-altitude hypoxia.
10.1089/ham.2016.0147
Long-Term Intermittent Work at High Altitude: Right Heart Functional and Morphological Status and Associated Cardiometabolic Factors.
Brito Julio,Siques Patricia,López Rosario,Romero Raul,León-Velarde Fabiola,Flores Karen,Lüneburg Nicole,Hannemann Juliane,Böger Rainer H
Frontiers in physiology
Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition. A cross-sectional study of 120 healthy miners working at an altitude of 4,400-4,800 m for over 5 years in 7-day commuting shifts was designed. Echocardiography was performed on day 2 at sea level. Additionally, biomedical and biochemical variables, Lake Louise scores (LLSs), sleep disturbances and physiological variables were measured at altitude and at sea level. The population was 41.8 ± 0.7 years old, with an average of 14 ± 0.5 (range 5-29) years spent at altitude. Most subjects still suffered from mild to moderate symptoms of acute mountain sickness (mild was an LLS of 3-5 points, including cephalea; moderate was LLS of 6-10 points) (38.3%) at the end of day 1 of the shift. Echocardiography showed a 23% mean pulmonary artery pressure (mPAP) >25 mmHg, 9% HAPH (≥30 mmHg), 85% mild increase in right ventricle wall thickness (≥5 mm), 64% mild right ventricle dilation, low pulmonary vascular resistance (PVR) and fairly good ventricle performance. Asymmetric dimethylarginine (ADMA) (OR 8.84 (1.18-66.39); < 0.05) and insulin (OR: 1.11 (1.02-1.20); < 0.05) were associated with elevated mPAP and were defined as a cut-off. Interestingly, the correspondence analysis identified association patterns of several other variables (metabolic, labor, and biomedical) with higher mPAP. Working intermittently at high altitude involves a distinctive pattern. The most relevant and novel characteristics are a greater prevalence of elevated mPAP and HAPH than previously reported at chronic intermittent hypobaric hypoxia (CIHH), which is accompanied by subsequent morphological characteristics. These findings are associated with cardiometabolic factors (insulin and ADMA). However, the functional repercussions seem to be minor or negligible. This research contributes to our understanding and surveillance of this unique model of chronic intermittent high-altitude exposure.
10.3389/fphys.2018.00248
The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives.
Stembridge Mike,Williams Alexandra M,Gasho Christopher,Dawkins Tony G,Drane Aimee,Villafuerte Francisco C,Levine Benjamin D,Shave Rob,Ainslie Philip N
Proceedings of the National Academy of Sciences of the United States of America
In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e., no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa, and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also was elevated in Sherpa compared with lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and in Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and toward a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude.
10.1073/pnas.1909002116
Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans.
American journal of human genetics
The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia. In contrast, high-altitude-adapted Quechua- and Aymara-speaking inhabitants of the Andean Altiplano are not protected from high-altitude polycythemia in the same way, yet they exhibit other adaptive features for which the genetic underpinnings remain obscure. Here, we used whole-genome sequencing to scan high-altitude Andeans for signals of selection. The genes showing the strongest evidence of selection-including BRINP3, NOS2, and TBX5-are associated with cardiovascular development and function but are not in the response-to-hypoxia pathway. Using association mapping, we demonstrated that the haplotypes under selection are associated with phenotypic variations related to cardiovascular health. We hypothesize that selection in response to hypoxia in Andeans could have vascular effects and could serve to mitigate the deleterious effects of polycythemia rather than reduce polycythemia itself.
10.1016/j.ajhg.2017.09.023
Alterations to cardiac morphology and function among high-altitude workers: a retrospective cohort study.
Han Shurong,Zhao Lin,Ma Shiwei,Chen Zhangjian,Wu Shiping,Shen Min,Xia Guobin,Jia Guang
Occupational and environmental medicine
OBJECTIVES:Exposure to high altitude can affect human health, including the development of adverse cardiovascular effects. This study aimed to investigate alterations in cardiac morphology and function in high-altitude workers and to identify risk factors associated with cardiac abnormalities. METHODS:A retrospective cohort study was conducted with 286 Qinghai-Tibetan Railroad maintenance workers. Participant data were collected from company personnel records. Data on echocardiography and diagnosis of cardiac abnormalities were extracted from participants' medical records. Time-to-event analysis was used to investigate the risk of cardiac abnormalities among participants with different baseline characteristics and identify risk factors associated with cardiac abnormalities that developed as a result of working at high altitude. RESULTS:A total of 173 participants had developed cardiac abnormalities during the follow-up period. The most common cardiac abnormality was right atrial enlargement, followed by left ventricular diastolic dysfunction and tricuspid regurgitation. Among participants with cardiac abnormalities, the median follow-up time was 17 months. Compared with participants who were younger than 20 years and working at altitude <4000 m, participants older at employment and working at extremely high altitude were more likely to develop cardiac abnormalities. Nearly 40% of the participants who worked at altitude <4000 m remained without cardiac abnormalities during the follow-up period. CONCLUSIONS:Over 60% of participants developed cardiac abnormalities after working at high altitude, predominantly right heart enlargement and left ventricular diastolic dysfunction. Age at employment and workplace altitude were significant risk factors for cardiac abnormalities. Enhanced regular physical examinations are recommended for high-altitude workers.
10.1136/oemed-2019-106108
The prognostic value of altitude in patients with heart failure with reduced ejection fraction.
Kaya Ahmet,Bayramoğlu Adil,Bektaş Osman,Yaman Mehmet,Günaydın Zeki Yüksel,Topcu Selim,Gülcü Oktay,Aksu Uğur,Kalkan Kamuran,Tanboğa Ibrahim
Anatolian journal of cardiology
OBJECTIVE:It is well known that the altitude may affect the cardiovascular system. However, there were a few data related to the effect of altitude on the adverse outcome in patients with heart failure with reduced ejection fraction (HFREF). The aim of the present study was to investigate the role of intermediate high altitude on the major adverse cardiovascular outcome in patients with HFREF. METHODS:Patients with HFREF admitted to the outpatient clinics at the first center at sea level and the second center at 1890 m were prospectively enrolled in the study. HFREF was defined as symptoms/signs of heart failure and left ventricular ejection fraction <40%. The major adverse cardiac outcome (MACE) was defined as all-cause death, stroke, and re-hospitalization due to heart failure. The median follow-up period of the study population was 27 months. RESULTS:The study included 320 (58.55% male, mean age 65.7±11.2 years) patients. The incidence of all-cause death was 8.5%, stroke 6.1%, re-hospitalization due to decompensated heart failure 34.3%, and MACE 48.9%. In Kaplan-Meier analysis, patients with HFREF living at high altitude had more MACE (71.1% vs. 25.3%, log rank p=0.005) and presented with more stroke (11.3% vs. 2.1%, log rank p=0.001) and re-hospitalization due to heart failure (65.1% vs. 20.1%, log rank p<0.001) rates than those at low altitude in the follow-up; however, the rate of all-cause death was similar (9.4% vs. 8.1%, log rank p=0.245). CONCLUSION:In the present study, we demonstrated that the intermediate high altitude is the independent predictor of MACE in patients with HFREF. High altitude may be considered as a risk factor in decompensating heart failure.
10.14744/AnatolJCardiol.2019.81535
[Altitude and the right heart].
Naeije R
Revue des maladies respiratoires
INTRODUCTION:Altitude is associated with a decrease in partial pressure of oxygen. Hypoxia induces pulmonary vasoconstriction with subsequent fixed increase in pulmonary artery pressure, and eventual right heart failure. CURRENT KNOWLEDGE:High altitude exposure is associated with an increase in pulmonary artery pressure that is proportional to initial vasoconstriction. Echocardiographic evaluations on a large number of subjects show that the altitude-induced increase in pulmonary pressure is generally modest and does not exceed the 25mmHg that are diagnostic of pulmonary hypertension. This does not greatly increase right ventricular afterload, so that imaging of the right ventricle only shows some alterations of indices of systolic or diastolic function, but preserved contractile reserve during exercise. In less than 1% of cases, hypoxic vasoconstriction is strong and may be a cause of severe pulmonary hypertension and right heart failure. PERSPECTIVES:The prognostic relevance of altitude-induced pulmonary hypertension and associated cardiac function alterations is not known. Treatment of hypoxic pulmonary hypertension relies on evacuation to a lower altitude, oxygen and pulmonary vasodilators. These treatment strategies have not been rigorously evaluated. CONCLUSIONS:Altitude may be a cause of right heart failure. This uncommon complication of altitude exposure requires further epidemiological and therapeutic studies.
10.1016/j.rmr.2017.01.013
Physiological Changes to the Cardiovascular System at High Altitude and Its Effects on Cardiovascular Disease.
Riley Callum James,Gavin Matthew
High altitude medicine & biology
Riley, Callum James, and Matthew Gavin. Physiological changes to the cardiovascular system at high altitude and its effects on cardiovascular disease. High Alt Med Biol. 18:102-113, 2017.-The physiological changes to the cardiovascular system in response to the high altitude environment are well understood. More recently, we have begun to understand how these changes may affect and cause detriment to cardiovascular disease. In addition to this, the increasing availability of altitude simulation has dramatically improved our understanding of the physiology of high altitude. This has allowed further study on the effect of altitude in those with cardiovascular disease in a safe and controlled environment as well as in healthy individuals. Using a thorough PubMed search, this review aims to integrate recent advances in cardiovascular physiology at altitude with previous understanding, as well as its potential implications on cardiovascular disease. Altogether, it was found that the changes at altitude to cardiovascular physiology are profound enough to have a noteworthy effect on many forms of cardiovascular disease. While often asymptomatic, there is some risk in high altitude exposure for individuals with certain cardiovascular diseases. Although controlled research in patients with cardiovascular disease was largely lacking, meaning firm conclusions cannot be drawn, these risks should be a consideration to both the individual and their physician.
10.1089/ham.2016.0112