Global REACH 2018: the adaptive phenotype to life with chronic mountain sickness and polycythaemia

Hansen, Alexander B.; Moralez, Gilbert; Amin, Sachin B.; Simspon, Lydia L.; Hofstaetter, Florian; Anholm, James D.; Gasho, Christopher; Stembridge, Mike; Dawkins, Tony G.; Tymko, Michael M.; Ainslie, Philip N.; Villafuerte, Francisco C.; Romero, Steven A.; Hearon, Christopher M.; Lawley, Justin S.

doi:10.1113/jp281730

Cited by 15 publications

(19 citation statements)

References 76 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…50—60% in healthy high-altitude residents, which is much higher than our corresponding finding (+23%; Table 3 ), while ( Oberholzer et al, 2020 ) showed a similar result (+17%) in residents at the same altitude as that of our study. Additionally, Claydon et al (2004) and Hansen et al (2021) reported absolute data similar to those in our study in high-altitude residents, but unfortunately, they did not present data for a SL control group. It is possible that intoxication with cobalt from the surrounding cobalt mines augments hypoxia-mediated erythropoiesis ( Jefferson et al, 2002 ) and contributes to the excessive erythrocytosis described by Lawrence et al (1952) and Hurtado (1960) .…”

Section: Discussionsupporting

confidence: 65%

“…While the classic studies ( Lawrence et al, 1952 ; Hurtado 1960 ) and also Hansen et al (2021) and Claydon et al (2004) showed that high-altitude values were similar to sea-level values, Oberholzer et al (2020) found 28% lower PV values in residents at 3,800 m than in control subjects at SL. For CMS patients, the classic studies ( Lawrence et al, 1952 ; Hurtado 1960 ) found a marked reduction in PV by approximately 40%, which was much lower than those described by Hansen et al (2021) (−16%) and Claydon et al (2004) (−9%, nonsignificant). Oberholzer et al (2020) did not find any difference between the HH and CMS groups.…”

Section: Discussionmentioning

confidence: 77%

See 1 more Smart Citation

Hemoglobin Mass and Blood Volume in Patients With Altitude-Related Polycythemia

et al. 2022

View full text Add to dashboard Cite

Patients with chronic mountain sickness (CMS) have a high hemoglobin concentration [Hb] due to increased hemoglobin mass (Hbmass) and possibly reduced plasma volume (PV). The values of Hbmass, PV and blood volume (BV) have been described differently, and the relationships between [Hb] and Hbmass or PV are poorly understood. This study obtained representative Hbmass, PV and BV data from healthy, high-altitude residents and CMS patients and quantified the dependency of [Hb] on Hbmass and PV. Methods: Eighty-seven subjects born at high altitude (∼3,900 m) were enrolled. Thirty-four had CMS (CMS), 11 had polycythemia without CMS (intermediate, IM), 20 were healthy highlanders (HH), and 22 living near sea level (SL, 420 m) served as the sea level (SL) control group. Hbmass, PV and BV were determined using a CO-rebreathing method modified for assessing polycythemia patients. Furthermore, [Hb], hematocrit (Hct), plasma erythropoietin concentration [EPO] and blood gas and acid–base status were determined. Results: In the HH group, Hbmass was 27% higher (940 ± 105 g) than in the SL group (740 ± 112 g) and 72% (1,617 ± 265 g) lower than in the CMS group. The PV in the HH group was similar to that in the SL group (−6%) and 15% higher than that in the CMS group (p < 0.001). In the HH group, the BV (5,936 ± 673 ml) did not differ from that in the SL group and was 28% lower than in the CMS group (7,606 ± 1075 ml, p < 0.001). Log [EPO] was slightly increased in the CMS group relative to the HH group (p < 0.01). All values in the IM group were between those in the HH and CMS groups. Hbmass and BV were positively correlated, and PV was negatively correlated with peripheral O2 saturation. Increased Hbmass and decreased PV contributed approximately 65 and 35%, respectively, to the difference in [Hb] between the HH (17.1 ± 0.8 g/dl) and CMS (22.1 ± 1.0 g/dl) groups. Conclusions: In CMS patients, the decrease in PV only partially compensated for the substantial increase in Hbmass, but it did not prevent an increase in BV; the decrease in PV contributed to an excessively high [Hb].

show abstract

Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 77%

Hemoglobin Mass and Blood Volume in Patients With Altitude-Related Polycythemia

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although exercise fatigue and reduced exercise capacity have been commonly reported in CMS patients, allegedly due to systemic or pulmonary haemodynamic burden and O 2 -diffusion impairment as a consequence of excessive haematocrit and blood viscosity (Letcher et al, 1981;Monge, 1943;Ostergaard, 2020;Pratali et al, 2012;Soria et al, 2019;Stuber et al, 2010;Winslow & Monge-C, 1987), several studies indirectly suggest that adaptive mechanisms exist to maintain O 2 transport in the face of a high haematocrit (Juvonen et al, 1991;Lindenfeld et al, 1985). We have previously shown that Andeans diagnosed with mild to moderate CMS can attain normal maximal aerobic capacities compared to healthy Andean controls in Cerro de Pasco (4340 m) (Groepenhoff et al, 2012), and we have also recently confirmed these findings and identified evidence for an adaptive phenotype for O 2 transport during exercise with EE (Hansen et al, 2021).…”

Section: New Findingssupporting

confidence: 74%

Sub‐maximal aerobic exercise training reduces haematocrit and ameliorates symptoms in Andean highlanders with chronic mountain sickness

Macarlupú

Vizcardo‐Galindo

Figueroa-Mujíca

et al. 2021

Experimental Physiology

View full text Add to dashboard Cite

Excessive erythrocytosis is the hallmark sign of chronic mountain sickness (CMS), a debilitating syndrome associated with neurological symptoms and increased cardiovascular risk. We have shown that unlike sedentary residents at the same altitude, trained individuals maintain haematocrit within sea-level range, and thus we hypothesise that aerobic exercise training (ET) might reduce excessive haematocrit and ameliorate CMS signs and symptoms. Eight highlander men (38 ± 12 years) with CMS (haematocrit: 70.6 ± 1.9%, CMS score: 8.8 ± 1.4) from Cerro de Pasco, Peru (4340 m) participated in the study. Baseline assessment included haematocrit, CMS score, pulse oximetry, maximal cardiopulmonary exercise testing and in-office plus 24 h ambulatory blood pressure (BP) monitoring. Blood samples were collected to assess cardiometabolic, erythropoietic, and haemolysis markers. ET consisted of pedalling exercise in a cycloergometer at 60% of VO 2 peak for 1 h/day, 4 days/week for 8 weeks, and participants were assessed at weeks 4 and 8. Haematocrit and CMS score decreased significantly by week 8 (to 65.6 ± 6.6%, and 3.5 ± 0.8, respectively, P < 0.05), while VO 2 peak and maximum workload increased with ET (33.8 ± 2.4 vs. 37.2 ± 2.0 ml/min/kg, P < 0.05; and 172.5 ± 9.4 vs. 210.0 ± 27.8 W, P < 0.01; respectively).Except for an increase in high-density lipoprotein cholesterol, other blood markers and BP showed no differences. Our results suggest that reduction of haematocrit and CMS symptoms results mainly from haemodilution due to plasma volume expansion rather than to haemolysis. In conclusion, we show that ET can effectively reduce haematocrit, ameliorate symptoms and improve aerobic capacity in CMS patients, suggesting that regular aerobic exercise might be used as a low-cost non-invasive and non-pharmacological management strategy.

show abstract

“…One is pulmonary arterial hypertension during mild exercise, sometimes even at rest, indicating altered haemodynamics. It remains to be elucidated to what extent this is due to the increased blood viscosity in polycythaemia alone or by other maladaptive responses in severe CMS such as the increased sympathetic tone, which was even found in mild CMS in the present study (Hansen et al 2021). It would thus be of interest to expand these studies to severe polycythaemia and/or CMS to test these possibilities.…”

mentioning

confidence: 78%

“…In this issue of The Journal of Physiology, Hansen et al (2021) present very interesting results from an elaborate and difficult to perform study trying to explain how the cardiovascular system manages to bring the viscous blood of polycythaemic high-altitude residents to working skeletal muscle to prevent loss of performance capacity. The significance of this study lies in its widespread applicability to various clinical/pathological situations in which tissue hypoxia occurs by decreased arterial oxygen load and/or by impaired tissue supply.…”

mentioning

confidence: 99%