EGLN1 variants influence expression and SaO2 levels to associate with high-altitude pulmonary oedema and adaptation

2012 ◽  
Vol 124 (7) ◽  
pp. 479-489 ◽  
Author(s):  
Aastha Mishra ◽  
Ghulam Mohammad ◽  
Tashi Thinlas ◽  
M. A. Qadar Pasha
Keyword(s):  
High Altitude ◽  
Pulmonary Oedema ◽  
Oxygen Sensor ◽  
Arterial Oxygen Saturation ◽  
Systolic Pressure ◽  
Inverse Correlation ◽  
Functional Adaptation ◽  
Arterial Oxygen ◽  
Pulmonary Artery Systolic Pressure ◽  
Association Analyses

EGLN1 [encoding HIF (hypoxia-inducible factor)-prolyl hydroxylase 2] plays a pivotal role in the HIF pathway and has emerged as one of the most intriguing genes with respect to physiology at HA (high altitude). EGLN1, being an actual oxygen sensor, appears to have a potential role in the functional adaptation to the hypobaric hypoxic environment. In the present study, we screened 30 polymorphisms of EGLN1, evaluated its gene expression and performed association analyses. In addition, the role of allelic variants in altering TF (transcription factor)-binding sites and consequently the replacement of TFs at these loci was also investigated. The study was performed in 250 HAPE-p [HAPE (HA pulmonary oedema)-patients], 210 HAPE-f (HAPE-free controls) and 430 HLs (healthy Ladakhi highland natives). The genotypes of seven polymorphisms, rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, differed significantly between HAPE-p and HAPE-f (P<0.008). The genotypes AA, TT, AA, GG, CC, AA and GG of rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252, prevalent in HAPE-p, were identified as risk genotypes and their counterpart homozygotes, prevalent in HLs, were identified as protective. EGLN1 expression was up-regulated 4.56-fold in HAPE-p (P=0.0084). The risk genotypes, their haplotypes and interacting genotypes were associated with up-regulated EGLN1 expression (P<0.05). Similarly, regression analysis showed that the risk alleles and susceptible haplotypes were associated with decreased SaO2 (arterial oxygen saturation) levels in the three groups. The significant inverse correlation of SaO2 levels with PASP (pulmonary artery systolic pressure) and EGLN1 expression and the association of these polymorphisms with SaO2 levels and EGLN1 expression contributed to uncovering the molecular mechanism underlying hypobaric hypoxic adaptation and maladaptation.

scholarly journals Effects of high altitude in pregnancy: an opportunity of research in KAHS

2018 ◽  
Vol 1 (3) ◽  
pp. 1-2
Author(s):  
Binod Aryal
Keyword(s):  
Birth Weight ◽  
South America ◽  
High Altitude ◽  
Work Performance ◽  
Arterial Oxygen Saturation ◽  
Functional Adaptation ◽  
European Ancestry ◽  
Arterial Oxygen ◽  
Adaptation To Hypoxia ◽  
Physiological Changes

Pregnancy is a special condition in a women’s life with unique physiological changes. There has been some research on physiological changes in human body in high altitude; however, there are many things still unknown about pregnancy at high altitude. It is an estimation that about 140 million people worldwide live in high altitude of above 2500 m, and it is believed that the hypobaric hypoxia of pregnancy at high altitude is the most common cause for maternofetal hypoxia. It has been seen that the babies born at high altitude are smaller, and the degree of smallness is inversely correlated with the number of generations of ancestors of high-altitude residence. Some studies show that women in populations with high-altitude ancestry, such as the Aymaras or Quechuas in South America and Tibetans in Asia, deliver heavier babies than women from European ancestry in South America or Han women in China living at high altitude. A study by Jensen and Moore shows that in Colorado, altitude acts as an independent factor in determining birth weight, with a reduction in birth weight of 100 g per 1000 m elevation gain. Studies have shown that low birth weight at high altitude has no association with socioeconomic status. Hence, it may reflect either hypoxia-induced intrauterine growth restriction or genetic adaptation. The latter implies a strong fetomaternal interaction involving adaptation to hypoxia on several levels. It also reflects the importance of interaction between the mother and the fetus which is stressed by the fact that better maternal ventilator response to hypoxic stress at high altitude correlates positively with birth weight. Another study shows that people living at altitudes of 4000 m and above have an arterial partial pressure of oxygen of 50 mmHg and an arterial oxygen saturation of just above 80%. There has been many studies on populations living in high-altitude regions for many generations, like Quechuas and Tibetans, which show many functional and structural adaptations in high altitude. This adaptation helps to allow for a way out for the main metabolic problem they face: maintaining an acceptably high scope for sustained aerobic metabolism despite reduced availability of oxygen in the inspired air. The functional adaptation to high altitude is measured indirectly by determining aerobic capacity, which reflects not only the maximum work performance but also the success of the individual’s biological oxygen transport system.

scholarly journals Continuous Aspiration Thrombectomy in High- and Intermediate-High-Risk Pulmonary Embolism in Real-World Clinical Practice

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Aleksander Araszkiewicz ◽  
Sylwia Sławek-Szmyt ◽  
Stanisław Jankiewicz ◽  
Bartosz Żabicki ◽  
Marek Grygier ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Low Dose ◽  
Mechanical Thrombectomy ◽  
Arterial Oxygen Saturation ◽  
Clinical Status ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Arterial Oxygen ◽  
Pulmonary Artery Systolic Pressure

Objectives. We sought to assess the technical and clinical feasibility of continuous aspiration catheter-directed mechanical thrombectomy (CDT) in patients with high- or intermediate-high-risk pulmonary embolism (PE). Methods and Results. Fourteen patients (eight women and six men; age range: 29–71 years) with high- or intermediate-high-risk PE and contraindications to or ineffective systemic thrombolysis were prospectively enrolled between October 2018 and February 2020. The Indigo Mechanical Thrombectomy System (Penumbra, Inc., Alameda, California) was used as CDT device. Low-dose local thrombolysis (alteplase, 3–12 mg) was additionally applied in three patients. Technical and procedural success was achieved in 14 patients (100%). Complete or nearly complete clearance of pulmonary arteries was achieved in nine patients (64.3%), whereas partial clearance was achieved in five (35.7%). A significant improvement in the pre- and postprocedural patients’ clinical status was observed in the following fields (median; interquartile range): heart rate (110; 100–120/min vs. 85; 80–90/min; p < 0.0001 ), systolic blood pressure (106; 90–127 mmHg vs. 123; 110–133 mmHg; p = 0.049 ), arterial oxygen saturation (88.5; 84.2–93% vs. 95.0; 93.8–95%, p = 0.0051 ), pulmonary artery systolic pressure (55; 44–66 mmHg vs. 42; 34–53 mmHg; p = 0.0015 ), Miller index score (21.5; 20–23 vs. 9.5; 8–13; p < 0.0001 ) and right ventricular/left ventricular ratio (1.3; 1.3–1.5 vs. 1.0; 0.9–1.0; p < 0.0001 ). No major periprocedural bleeding was detected. Conclusions. CDT is a feasible and promising technique for management of high- or intermediate-high-risk PE to decrease thrombus burden, reduce right heart strain, and improve hemodynamic and clinical status. Some patients may benefit from simultaneous local low-dose thrombolytic therapy. Nevertheless, its criteria and role in CTD-managed patients require further elucidation.

Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise

2010 ◽  
Vol 109 (5) ◽  
pp. 1307-1317 ◽  
Author(s):  
André La Gerche ◽  
Andrew I. MacIsaac ◽  
Andrew T. Burns ◽  
Don J. Mooney ◽  
Warrick J. Inder ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Maximal Exercise ◽  
Arterial Oxygen Saturation ◽  
Maximal Oxygen Consumption ◽  
Systolic Pressure ◽  
Arterial Oxygen ◽  
Pulmonary Artery Systolic Pressure ◽  
Peak Exercise ◽  
Similar Proportion ◽  
Vascular Reserve

Pulmonary transit of agitated contrast (PTAC) occurs to variable extents during exercise. We tested the hypothesis that the onset of PTAC signifies flow through larger-caliber vessels, resulting in improved pulmonary vascular reserve during exercise. Forty athletes and fifteen nonathletes performed maximal exercise with continuous echocardiographic Doppler measures [cardiac output (CO), pulmonary artery systolic pressure (PASP), and myocardial velocities] and invasive blood pressure (BP). Arterial gases and B-type natriuretic peptide (BNP) were measured at baseline and peak exercise. Pulmonary vascular resistance (PVR) was determined as the regression of PASP/CO and was compared according to athletic and PTAC status. At peak exercise, athletes had greater CO (16.0 ± 2.9 vs. 12.4 ± 3.2 l/min, P < 0.001) and higher PASP (60.8 ± 12.6 vs. 47.0 ± 6.5 mmHg, P < 0.001), but PVR was similar to nonathletes ( P = 0.71). High PTAC (defined by contrast filling of the left ventricle) occurred in a similar proportion of athletes and nonathletes (18/40 vs. 10/15, P = 0.35) and was associated with higher peak-exercise CO (16.1 ± 3.4 vs. 13.9 ± 2.9 l/min, P = 0.010), lower PASP (52.3 ± 9.8 vs. 62.6 ± 13.7 mmHg, P = 0.003), and 37% lower PVR ( P < 0.0001) relative to low PTAC. Right ventricular (RV) myocardial velocities increased more and BNP increased less in high vs. low PTAC subjects. On multivariate analysis, maximal oxygen consumption (V̇o2max) ( P = 0.009) and maximal exercise output ( P = 0.049) were greater in high PTAC subjects. An exercise-induced decrease in arterial oxygen saturation (98.0 ± 0.4 vs. 96.7 ± 1.4%, P < 0.0001) was not influenced by PTAC status ( P = 0.96). Increased PTAC during exercise is a marker of pulmonary vascular reserve reflected by greater flow, reduced PVR, and enhanced RV function.

Hypoxia-induced intrapulmonary arteriovenous shunting at rest in healthy humans

2010 ◽  
Vol 109 (4) ◽  
pp. 1072-1079 ◽  
Author(s):  
Steven S. Laurie ◽  
Ximeng Yang ◽  
Jonathan E. Elliott ◽  
Kara M. Beasley ◽  
Andrew T. Lovering
Keyword(s):  
Mixture Fraction ◽  
Contrast Echocardiography ◽  
Arterial Oxygen Saturation ◽  
Systolic Pressure ◽  
Arterial Oxygen ◽  
Pulmonary Artery Systolic Pressure ◽  
Arteriovenous Shunting ◽  
Healthy Humans ◽  
Four Levels ◽  
Fraction Of Inspired Oxygen

Intrapulmonary arteriovenous (IPAV) shunting has been shown to occur at rest in some subjects breathing a hypoxic gas mixture [fraction of inspired oxygen (FiO2) = 0.12] for brief periods of time. In the present study we set out to determine if IPAV shunting could be induced at rest in all subjects exposed to hypoxia for 30 min. Twelve subjects (6 women) breathed four levels of hypoxia (FiO2 = 0.16, 0.14, 0.12, and 0.10) for 30 min each in either an ascending or descending order with a 15-min normoxic break between bouts. Saline contrast echocardiography was used to detect IPAV shunt and a shunt score (0–5) was assigned based on contrast in the left ventricle with a shunt score ≥ 2 considered significant. Pulmonary artery systolic pressure (PASP) was determined using Doppler ultrasound. The total number of subjects demonstrating shunt scores ≥ 2 for FiO2 = 0.16, 0.14, 0.12, and 0.10 was 1/12, 7/12, 9/12, and 12/12, respectively. Shunt scores were variable between subjects but significantly greater than normoxia for FiO2 = 0.12 and 0.10. Shunt scores correlated with peripheral measurements of arterial oxygen saturation (SpO2) ( r w = −0.67) and PASP ( r w = 0.44), despite an increased shunt score but no increase in PASP while breathing an FiO2 = 0.12. It is unknown how hypoxia induces the opening of IPAV shunts, but these vessels may be controlled via similar mechanisms as systemic vessels that vasodilate in response to hypoxia. Despite intersubject variability our results indicate significant IPAV shunting occurs at rest in all subjects breathing an FiO2 = 0.10 for 30 min.

scholarly journals Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise

2020 ◽  
Vol 120 (12) ◽  
pp. 2693-2704
Author(s):  
Erika Schagatay ◽  
Alexander Lunde ◽  
Simon Nilsson ◽  
Oscar Palm ◽  
Angelica Lodin-Sundström
Keyword(s):  
High Altitude ◽  
Acute Hypoxia ◽  
Arterial Oxygen Saturation ◽  
Hemoglobin Concentration ◽  
Step Test ◽  
Arterial Oxygen ◽  
Spleen Volume ◽  
Spleen Contraction ◽  
Response To Exercise ◽  
Rest And Exercise

Abstract Purpose Hypoxia and exercise are known to separately trigger spleen contraction, leading to release of stored erythrocytes. We studied spleen volume and hemoglobin concentration (Hb) during rest and exercise at three altitudes. Methods Eleven healthy lowlanders did a 5-min modified Harvard step test at 1370, 3700 and 4200 m altitude. Spleen volume was measured via ultrasonic imaging and capillary Hb with Hemocue during rest and after the step test, and arterial oxygen saturation (SaO2), heart rate (HR), expiratory CO2 (ETCO2) and respiratory rate (RR) across the test. Results Resting spleen volume was reduced with increasing altitude and further reduced with exercise at all altitudes. Mean (SE) baseline spleen volume at 1370 m was 252 (20) mL and after exercise, it was 199 (15) mL (P < 0.01). At 3700 m, baseline spleen volume was 231 (22) mL and after exercise 166 (12) mL (P < 0.05). At 4200 m baseline volume was 210 (23) mL and after exercise 172 (20) mL (P < 0.05). After 10 min, spleen volume increased to baseline at all altitudes (NS). Baseline Hb increased with altitude from 138.9 (6.1) g/L at 1370 m, to 141.2 (4.1) at 3700 m and 152.4 (4.0) at 4200 m (P < 0.01). At all altitudes Hb increased from baseline during exercise to 146.8 (5.7) g/L at 1370 m, 150.4 (3.8) g/L at 3700 m and 157.3 (3.8) g/L at 4200 m (all P < 0.05 from baseline). Hb had returned to baseline after 10 min rest at all altitudes (NS). The spleen-derived Hb elevation during exercise was smaller at 4200 m compared to 3700 m (P < 0.05). Cardiorespiratory variables were also affected by altitude during both rest and exercise. Conclusions The spleen contracts and mobilizes stored red blood cells during rest at high altitude and contracts further during exercise, to increase oxygen delivery to tissues during acute hypoxia. The attenuated Hb response to exercise at the highest altitude is likely due to the greater recruitment of the spleen reserve during rest, and that maximal spleen contraction is reached with exercise.

Long-term results after palliative intra-cardiac repair for tetralogy of Fallot and diminutive pulmonary arteries

2019 ◽  
Vol 29 (8) ◽  
pp. 1036-1039
Author(s):  
Yoichi Kawahira ◽  
Kyoichi Nishigaki ◽  
Koji Kagisaki ◽  
Takuji Watanabe ◽  
Kazuki Tanimoto
Keyword(s):  
Right Ventricle ◽  
Tetralogy Of Fallot ◽  
Arterial Oxygen Saturation ◽  
Pulmonary Arteries ◽  
Systolic Pressure ◽  
Cardiac Repair ◽  
Long Term Results ◽  
Arterial Oxygen ◽  
The Right

AbstractBackground:In patients with tetralogy of Fallot with the diminutive pulmonary arteries, we sometimes have to give up the complete intra-cardiac repair due to insufficient growth of the pulmonary arteries. We have carried out palliative intra-cardiac repair using a fenestrated patch.Methods:Of all 202 patients with tetralogy of Fallot in our centre since 1996, five patients (2.5%) with the diminutive pulmonary arteries underwent palliative intra-cardiac repair using a fenestrated patch. Mean operative age was 1.8 years. Previous operation was Blalock–Taussig shunt in 4. At operation, the ventricular septal defect was closed using a fenestrated patch and the right ventricular outflow tract was enlarged. Follow-up period was 9.8 ± 2.6 years.Results:There were no operative and late deaths. Fenestration closed spontaneously on its own in four patients 2.7 ± 2.1 years after the intra-cardiac repair with a stable haemodynamics; however, the last patient with the smallest pulmonary artery index had supra-systemic pressure of the right ventricle post-operatively. The fenestration was emergently enlarged. Systemic arterial oxygen saturation was significantly and dramatically increased from 83.5 to 94% after the palliative intra-cardiac repair, and to 98% at the long term. A ratio of systolic pressure of the right ventricle to the left was significantly decreased to 0.76 ± 0.12 at the long term. Now all five patients were Ross classification class I.Conclusion:Although frequent catheter and surgical interventions were needed after the palliative intra-cardiac repair, this repair might be a choice improving quality of life with good results in patients with tetralogy of Fallot associated with the diminutive pulmonary arteries.

P6480Asymmetric dimethylarginine (ADMA) predicts altitude-associated hypoxic pulmonary arterial hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R H Boeger ◽  
P Siques ◽  
J Brito ◽  
E Schwedhelm ◽  
E Pena ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Logistic Regression ◽  
Oxygen Saturation ◽  
High Altitude ◽  
Sea Level ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen ◽  
Arterial Blood ◽  
Pulmonary Arterial

Abstract Prolonged exposure to altitude-associated chronic hypoxia (CH) may cause high altitude pulmonary hypertension (HAPH). Chronic intermittent hypobaric hypoxia (CIH) occurs in individuals who commute between sea level and high altitude. CIH is associated with repetitive acute hypoxic acclimatization and conveys the long-term risk of HAPH. As nitric oxide (NO) is an important regulator of systemic and pulmonary vascular tone and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis that increases in hypoxia, we aimed to investigate whether ADMA predicts the incidence of HAPH among Chilean frontiers personnel exposed to six months of CIH. We performed a prospective study of 123 healthy male subjects who were subjected to CIH (5 days at appr. 3,550 m, followed by 2 days at sea level) for six months. ADMA, SDMA, L-arginine, arterial oxygen saturation, systemic arterial blood pressure, and haematocrit were measured at baseline and at months 1, 4, and 6 at high altitude. Acclimatization to high altitude was determined using the Lake Louise Score and the presence of acute mountain sickness (AMS). Echocardiography was performed after six months of CIH in a subgroup of 43 individuals with either good (n=23) or poor (n=20) aclimatization to altitude, respectively. Logistic regression was used to assess the association of biomarkers with HAPH. 100 study participants aged 18.3±1.3 years with complete data sets were included in the final analysis. Arterial oxygen saturation decreased upon the first ascent to altitude and plateaued at about 90% during the further course of the study. Haematocrit increased to about 47% after one month and remained stable thereafter. ADMA continuously increased and SDMA decreased during the study course, whilst L-arginine levels showed no distinct pattern. The incidence of AMS and the Lake Louise Score were high after the first ascent (53 and 3.1±2.4, respectively) and at one month of CIH (47 and 3.0±2.6, respectively), but decreased to 20 and 1.4±2.0 at month 6, respectively (both p<0.001 for trend). In echocardiography, 18 participants (42%) showed a mean pulmonary arterial pressure (mPAP) greater than 25 mm Hg (mean ± SD, 30.4±3.9 mm Hg), out of which 9 (21%) were classified as HAPH (mPAP ≥30 mm Hg; mean ± SD, 33.9±2.2 mm Hg). Baseline ADMA, but not SDMA, was significantly associated with mPAP at month 6 in univariate logistic regression analysis (R = 0.413; p=0.007). In ROC analysis, a cut-off for baseline ADMA of 0.665 μmol/l was determined as the optimal cut-off level to predict HAPH (mPAP >30 mm Hg) with a sensitivity of 100% and a specificity of 63.6%. ADMA concentration increases during long-term CIH. It is an independent predictive biomarker for the incidence of HAPH. SDMA concentration decreases during CIH and shows no association with HAPH. Our data support a role of impaired NO-mediated pulmonary vasodilation in the pathogenesis of high altitude pulmonary hypertension. Acknowledgement/Funding CONICYT/FONDEF/FONIS Sa 09I20007; FIC Tarapaca BIP 30477541-0; BMBF grant 01DN17046 (DECIPHER); Georg & Jürgen Rickertsen Foundation, Hamburg

scholarly journals Associations between arterial oxygen saturation, body size and limb measurements among high-altitude andean children

2013 ◽  
Vol 25 (5) ◽  
pp. 629-636 ◽  
Author(s):  
Emma Pomeroy ◽  
Jay T. Stock ◽  
Sanja Stanojevic ◽  
J. Jaime Miranda ◽  
Tim J. Cole ◽  
...  
Keyword(s):  
Body Size ◽  
Oxygen Saturation ◽  
High Altitude ◽  
Arterial Oxygen Saturation ◽  
Arterial Oxygen
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