Performance in the Six-Minute Walking Test Does Not Discriminate Excessive Erythrocytosis Patients in a Severe Hypoxic Environment.

BACKGROUND: Chronic exposure to severe hypoxia causes an increase in hematocrit (Hct) and hemoglobin concentration ([Hb]), which can lead to excessive erythrocytosis (EE) and impact physical performance. This work aims to determine the differences in the six-minute walking test (6MWT) between EE and healthy subjects residing at more than 5000 m. METHODS: A prospective, cross-sectional study was performed on 71 men (36 healthy and 25 suffering from EE) living in La Rinconada, Peru (5100 m). Basal levels of [Hb] and Hct were obtained. All the subjects performed the 6MWT, and distance reached, vital signs, dyspnea, and fatigue (Borg scale) at the end of the test were recorded. RESULTS: The average [Hb] and Hct levels in the control group were 18.7 ± 1.2 g/dL and 60.4 ± 7.1%, respectively, contrasting with EE subjects, who showed 23.4 ± 1.6 g/dL and 73.6 ± 5.9% (p < 0.001). However, no statistically significant differences were observed in BMI or other anthropometric parameters. At the end of the 6MWT, the distance traveled and vital constants were similar between both groups, except for arterial oxygen saturation, which was consistently lower in subjects with EE throughout the test. CONCLUSION: EE does not significantly affect 6MWT performance at high altitudes, nor the hemodynamic control during moderate aerobic exercise of subjects who live permanently in a severely hypoxic environment.

Blood viscosity and its determinants in the highest city in the world.

KEY POINTS: Highlanders develop unique adaptative mechanisms to chronic hypoxic exposure, including substantial haemoglobin and haematocrit increases. However, a significant proportion of populations living permanently at high altitude develop maladaptive features known as chronic mountain sickness (CMS). This study aimed to assess the effects of permanent life at high altitude on clinical and haemorheological parameters (blood viscosity and red blood cell aggregation) and to compare clinical and haemorheological parameters of dwellers from the highest city in the world according to CMS severity. Blood viscosity increased with altitude, together with haemoglobin concentration and haematocrit. At 5100 m, highlanders with moderate-to-severe CMS had higher blood viscosity mainly at high shear rate and even at corrected haematocrit (40%), with a lower red blood cell aggregation. Blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit. ABSTRACT: Chronic mountain sickness (CMS) is a condition characterised by excessive erythrocytosis (EE). While EE is thought to increase blood viscosity and subsequently to trigger CMS symptoms, the exact relationship between blood viscosity and CMS symptoms remains incompletely understood. We assessed the effect of living at high altitude on haemoglobin, haematocrit and haemorheological parameters (blood viscosity and red blood cell aggregation), and investigated their relationship with CMS in highlanders living in the highest city in the world (La Rinconada, Peru, 5100 m). Ninety-three men participated in this study: 10 Caucasian lowlanders, 13 Andean highlanders living at 3800 m and 70 Andean highlanders living at 5100 m (35 asymptomatic, CMS score ≤5; 15 with mild CMS, CMS score between 6 and 10; 20 with moderate-to-severe CMS, CMS score >10). Blood viscosity was measured at native and corrected haematocrit (40%). Haemoglobin concentration and haematocrit increased with the altitude of residency. Blood viscosity also increased with altitude (at 45 s-1 : 6.7 ± 0.9 mPa s at sea level, 14.0 ± 2.0 mPa s at 3800 m and 27.1 ± 8.8 mPa s at 5100 m; P < 0.001). At 5100 m, blood viscosity at corrected haematocrit was higher in highlanders with moderate-to-severe CMS (at 45 s-1 : 18.9 ± 10.7 mPa s) than in highlanders without CMS (10.2 ± 5.9 mPa s) or with mild CMS (12.1 ± 6.1 mPa s) (P < 0.05). In conclusion, blood viscosity may contribute to CMS symptomatology but the increased blood viscosity in CMS patients cannot solely be explained by the rise in haematocrit.

Plasma Proteomics of Ladakhi Natives Reveal Functional Regulation Between Renin-Angiotensin System and eNOS-cGMP Pathway.

Padhy, Gayatri, Anamika Gangwar, Manish Sharma, Kalpana Bhargava, and Niroj Kumar Sethy. Plasma proteomics of Ladakhi natives reveal functional regulation between renin-angiotensin system and eNOS-cGMP pathway. High Alt Med Biol. 18:27-36, 2017.-Humans have been living in high altitudes for more than 25,000 years but the molecular pathways promoting survival and performance in these extreme environments are not well elucidated. In an attempt to understand human adaptation to high altitudes, we used two-dimensional gel electrophoresis combined with MALDI-TOF/TOF to identify plasma proteins and associated pathways of ethnic Ladakhi natives residing at 3520 m. This resulted in the identification of 36 differential proteins compared with sea-level individuals. Proteins belonging to coagulation cascade and complement activation were found to be less abundant in Ladakhi natives. Interestingly, we observed lower abundance of angiotensinogen (ANGT) and subsequent analysis also revealed lower levels of both ANGT and angiotensin II (Ang II) in Ladakhi natives. Concomitantly, we observed elevated levels of eNOS, phosphorylated eNOS (Ser1177), and plasma biomarkers for nitric oxide (NO) production (nitrate and nitrite) and availability (cGMP). These results suggest that functional interplay between renin-angiotensin system and NO-cGMP pathway contributes to the hypoxia adaptation in Ladakhi natives. These findings will augment the present understanding of higher NO and NO-derived metabolite availability during human adaptation to high altitude.