High Altitude Pulmonary Edema in a Mining Worker With an Abnormal Rise in Pulmonary Artery Pressure in Response to Acute Hypoxia Without Prior History of High Altitude Pulmonary Edema.

High altitude pulmonary edema (HAPE) is a potentially life-threatening form of noncardiogenic pulmonary edema that may develop in otherwise healthy individuals upon ascent to high altitude. A constitutional susceptibility has been noted in some individuals, whereas others appear not to be susceptible at all. In our report, we present a case of HAPE triggered by concurrent respiratory tract infection and strenuous exercise in a mining worker with an abnormal rise in pulmonary artery pressure in response to acute hypoxia, without a prior history of HAPE during almost a year of commuting between high altitude and lowland areas.

Circulating Microparticles Are Differentially Increased in Lowlanders and Highlanders with High Altitude Induced Pulmonary Hypertension during the Cold Season.

The role of microparticles (MPs) and cold in high altitude pulmonary hypertension (HAPH) remains unexplored. We investigated the impact of long-term cold exposure on the pulmonary circulation in lowlanders and high-altitude natives and the role of MPs. Pulmonary hemodynamics were evaluated using Doppler echocardiography at the end of the colder and warmer seasons. We further examined the miRNA content of MPs isolated from the study participants and studied their effects on human pulmonary artery smooth muscle (hPASMCs) and endothelial cells (hPAECs). Long-term exposure to cold environment was associated with an enhanced pulmonary artery pressure in highlanders. Plasma levels of CD62E-positive and CD68-positive MPs increased in response to cold in lowlanders and HAPH highlanders. The miRNA-210 expression contained in MPs differentially changed in response to cold in lowlanders and highlanders. MPs isolated from lowlanders and highlanders increased proliferation and reduced apoptosis of hPASMCs. Further, MPs isolated from warm-exposed HAPH highlanders and cold-exposed highlanders exerted the most pronounced effects on VEGF expression in hPAECs. We demonstrated that prolonged exposure to cold is associated with elevated pulmonary artery pressures, which are most pronounced in high-altitude residents. Further, the numbers of circulating MPs are differentially increased in lowlanders and HAPH highlanders during the colder season.

An Exaggerated Rise in Pulmonary Artery Pressure in a High-Altitude Dweller during the Cold Season.

Chronic hypoxia-induced sustained pulmonary vasoconstriction and vascular remodeling lead to mild-to-moderate elevation of pulmonary artery pressure in high-altitude residents. However, in some of them, severe pulmonary hypertension may develop. Besides hypoxia, high-altitude residents also face other environmental challenges such as low ambient temperatures. We describe a case of a 49-year-old woman of Kyrgyz ethnicity with abnormally increased pulmonary artery pressure, revealed by Doppler echocardiography. Significantly elevated pulmonary artery pressure was detected in late winter and this was not associated with right ventricular hypertrophy or right ventricular dysfunction. Repeat echocardiography performed in late summer disclosed a significant attenuation of pulmonary artery pressure elevation, with no changes in right ventricular performance parameters. This case illustrates that, in susceptible individuals, long-term cold exposure could induce an abnormal pulmonary artery pressure rise, which can be reversed during warm seasons as in our patient. In certain circumstances, however, additional factors could contribute to a sustained pulmonary artery pressure increase and the development of persistent pulmonary hypertension, which often leads to right heart failure and premature death.

Cardiac Acclimatization at High Altitude in Two Different Ethnicity Groups.

Gaur, Priya, Meerim Sartmyrzaeva, Abdirashit Maripov, Kubatbek Muratali Uulu, Supriya Saini, Koushik Ray, Krishna Kishore, Almaz Akunov, Akpay Sarybaev, Bhuvnesh Kumar, Shashi Bala Singh, and Praveen Vats. Cardiac acclimatization at high altitude in two different ethnicity groups. High Alt Med Biol. 22:58-69, 2021. Introduction: High altitude (HA) exposure causes substantial increase in pulmonary artery pressure (PAP) and resistance. However, the effects of HA hypoxia exposure on cardiac function remain incompletely understood. Studies evaluating interethnic differences in cardiac functions in response to HA exposure are lacking. We aimed to compare the cardiac performance in Indian versus Kyrgyz healthy lowland subjects over the course of a 3-week HA exposure at 4,111 m. Methodology: Ten Indians and 20 Kyrgyz subjects were studied to assess cardiac acclimatization noninvasively by echocardiography in two different ethnic groups for 3 weeks of stay at HA. Pulmonary hemodynamics, right and left ventricular functions were evaluated at basal and on days 3, 7, 14, and 21 of HA exposure and on day 3 of deinduction. Results: HA exposure significantly increased PAP, pulmonary vascular resistance, cardiac output (CO), and heart rates (HRs) in both groups. Tricuspid regurgitant gradient increased significantly in both the group at day 3 versus basal; 38.9 mmHg (31.8, 42.9) versus 21.9 mmHg (19.5, 22.6) in Kyrgyz; and 34.1 mmHg (30.2, 38.5) versus 20.4 mmHg (19.7, 21.3) in Indians. HR increased significantly in Indians at day 3 and 7, whereas in Kyrgyz throughout exposure. CO increased significantly in both groups at day 3 versus basal with 5.9 L/min (5.5, 6.4) versus 5.1 L/min (4.4, 5.9) in Kyrgyz, and 5.7 L/min (5.56, 5.98) versus 4.9 L/min (4.1, 5.3) in Indians. Both groups exhibited preserved right ventricular diastolic and systolic functions at HAs. HA exposure changed the left ventricular diastolic parameters only in Kyrgyz subjects with impaired mitral inflow E/A, but not in Indian subjects. All cardiac changes induced at HAs have been recovered fully upon deinduction in both, except lateral-septal A', which remained low in Indians. Conclusion: Although pulmonary hemodynamics responses were similar in both groups, there were differences in cardiac functional parameters between the two in response to HA exposure that may be accounted to ethnic variation.

A Case of Chronic Thromboembolic Pulmonary Hypertension in a High-Altitude Dweller.

Chronic hypoxia causes sustained pulmonary vasoconstriction and vascular remodeling leading to development of pulmonary hypertension in high-altitude residents. Although pulmonary hypertension is of mild to moderate degrees in most cases, some high-altitude residents may develop severe pulmonary hypertension. We report a case of a 47-year-old female highlander of Kyrgyz ethnicity who presented with exertional breathlessness and echocardiographic signs of severe pulmonary hypertension, who was diagnosed as having chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, this is the first documented case of severe CTEPH in a high-altitude dweller. This case illustrates that causes other than hypoxia may underlie and/or contribute to severe pulmonary hypertension in residents of high altitude.

Circulating Apoptotic Signals During Acute and Chronic Exposure to High Altitude in Kyrgyz Population.

Background: Circulating apoptotic signals (CASs) have been described in the pathologies associated with dysregulated apoptosis, such as cancer, heart diseases, and pulmonary hypertension (PH). However, nothing is known about the expression profiles of these markers in the circulation of humans exposed to acute and chronic effects of high altitude (HA). Methods: Gene expression levels of different apoptotic signals (ASs) were analyzed in human pulmonary artery smooth muscle cells (PASMCs) upon hypoxia incubation. In addition, we measured the plasma values of relevant CAS in Kyrgyz volunteers during acute and chronic exposure to HA. Finally, we analyzed the effects of pro-apoptotic mediator Fas ligand (FasL) on apoptosis and proliferation of human PASMCs. Results: Several cellular AS were increased in PASMCs exposed to hypoxia, in comparison to normoxia condition. Among analyzed CAS, there was a prominent reduction of FasL in lowlanders exposed to HA environment. Furthermore, decreased circulatory levels of FasL were found in highlanders with HA-induced PH (HAPH), as compared to the lowland controls. Furthermore, FasL concentration in plasma negatively correlated with tricuspid regurgitant gradient values. Finally, FasL exerted pro-apoptotic and anti-proliferative effects on PASMCs. Conclusion: Our data demonstrated that circulating levels of FasL are reduced during acute and chronic exposure to HA environment. In addition, dysregulated FasL may play a role in the context of HAPH due to its relevant functions on apoptosis and proliferation of PASMCs.

Pulmonary Vascular Pressure Response to Acute Cold Exposure in Kyrgyz Highlanders.

Background/Aims: Long-term high altitude residence leads to a sustained increase in pulmonary vascular resistance and elevation of pulmonary artery pressure due to chronic alveolar hypoxia. However, living at high altitude is also associated with other environmental factors such as cold. There is still little experimental evidence suggesting detrimental effects of low temperatures on the pulmonary vasculature. Therefore, our objective was to investigate acute effects of cold exposure on the pulmonary circulation in Kyrgyz high altitude natives. Methods: Responses of the pulmonary circulation during acute exposure to controlled cold conditions (4°C-6°C) for 60 minutes were measured in highlanders using Doppler echocardiography. Based on the Doppler echocardiography-derived tricuspid regurgitant systolic pressure gradient (TRG), subjects with TRG ≥40 mmHg were allocated into the pulmonary hypertension (PH) group. Participants from the PH group were compared with volunteer control subjects with TRG <40 mmHg. All baseline measurements were evaluated in a warm room during 60 minutes (22°C-28°C). Following baseline echocardiography, the subjects were assigned to either warm or cold exposure for an additional 60 minutes. Results: Acute cold exposure significantly increased TRG both in the control (ΔTRG, 4.93 mmHg) and in the PH (ΔTRG, 8.15 mmHg) group, compared to the respective warm exposure conditions (ΔTRG, -0.14 and -0.05 mmHg). No changes in cardiac output were observed upon cold exposure. Conclusion: Thus, acute exposure to cold leads to elevation of pulmonary artery pressure in high altitude residents.

A Case of Subacute Infantile Mountain Sickness in a Kyrgyz Child.

Muratali Uulu, Kubatbek, Meerim Cholponbaeva, Melis Duishobaev, Aidana Toktosunova, Abdirashit Maripov, Akylbek Sydykov, and Akpay Sarybaev. A case of subacute infantile mountain sickness in a Kyrgyz child. High Alt Med Biol. 19:208-210, 2018.-Subacute infantile mountain sickness (SIMS) is a syndrome of severe pulmonary hypertension and right heart failure that develops in infants born in the lowlands and subsequently brought to live at high altitudes. Earlier postmortem studies have demonstrated significant remodeling of small pulmonary arteries as well as right ventricular hypertrophy and dilatation. In this report, we present a case of SIMS in a Kyrgyz child born to a native highlander mother evaluated by conventional echocardiography and tissue Doppler imaging. An echocardiogram showed severe pulmonary hypertension, a markedly dilated right ventricle with flattening of interventricular septum, and right ventricular dysfunction. To our knowledge, this is the first report of noninvasive imaging of pulmonary circulation and right ventricle in an infant with SIMS and confirmed the diagnosis using echocardiography.

Right Ventricular Remodeling and Dysfunction in Obstructive Sleep Apnea: A Systematic Review of the Literature and Meta-Analysis.

BACKGROUND: Recent studies have reported that obstructive sleep apnea (OSA) patients present alterations in right ventricular (RV) structure and function. However, large randomized controlled trials evaluating the impact of OSA on the right ventricle are lacking. METHODS: A comprehensive electronic database (PubMed, Web of Science, and Google Scholar) and reference search up to October 30, 2016, was performed. A systematic review and meta-analysis were performed to assess RV structure and function in OSA patients based on conventional echocardiography and tissue Doppler imaging. RESULTS: Twenty-five studies with 1,503 OSA patients and 796 controls were included in this study. OSA patients exhibited an increase in RV internal diameter (weighted mean difference (WMD) (95% confidence intervals (CIs)) 2.49 (1.62 to 3.37); p = 0.000) and RV wall thickness (WMD (95% CIs) 0.82 (0.51 to 1.13); p = 0.000). Furthermore, OSA patients had a significantly elevated RV myocardial performance index (WMD (95% CI) 0.08 (0.06 to 0.10); p = 0.000), decreased RV S' (WMD (95% CI) -0.95 (-1.59 to -0.32); p = 0.003), tricuspid annular plane systolic excursion (WMD (95% CI) -1.76 (-2.73 to -0.78); p = 0.000), and RV fractional area change (WMD (95% CI) -3.16 (-5.60 to -0.73); p = 0.011). CONCLUSION: OSA patients display RV dilatation, increased wall thickening, and altered RV function.