Global REACH 2018: Andean highlanders, chronic mountain sickness and the integrative regulation of resting blood pressure

Abstract

The high-altitude maladaptation syndrome chronic mountain sickness (CMS) is characterized by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, during the 2018 Global REACH expedition to Cerro de Pasco, Peru (4383 m), we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in eight Andean natives with CMS ([Hb] 22.6 ± 0.9 g⋅dL −1) and seven healthy highlanders ([Hb] 19.3 ± 0.8 g⋅dL −1). R-R interval (RRI, electrocardiogram), beat-by-beat BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA; microneurography) were recorded at rest and during pharmacologically induced changes in BP (modified Oxford test). Although [Hb] and blood viscosity (7.8 ± 0.7 vs. 6.6 ± 0.7 cP; d = 1.7, P = 0.01) were elevated in CMS compared to healthy highlanders, cardiac output, total peripheral resistance and mean BP were similar between groups. The vascular sympathetic baroreflex MSNA set-point (i.e. MSNA burst incidence) and reflex gain (i.e. responsiveness) were also similar between groups (MSNA set-point, d = 0.75, P = 0.16; gain, d = 0.2, P = 0.69). In contrast, in CMS the cardiovagal baroreflex operated around a longer RRI (960 ± 159 vs. 817 ± 50 ms; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs. 8.8 ± 2.6 ms⋅mmHg −1 ; d = 1.8, P = 0.01) versus healthy highlanders. Basal sympathetic vasomotor activity was also lower compared to healthy highlanders (33 ± 11 vs. 45 ± 13 bursts⋅min −1 ; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

A sympathetic view of blood pressure control at high altitude: new insights from microneurographic studies

“…Excessive erythrocyte volume, and the resulting elevations in haematocrit and blood viscosity, increase resistance to blood flow, exacerbate ventilation–perfusion mismatch and impair pulmonary gas exchange (Winslow et al., 1985), which further exacerbates arterial hypoxaemia. Despite lower arterial oxygen tensions and saturations, Simpson et al (2021) reported a 25% lower MSNA burst frequency in Andeans with mild CMS, compared to healthy Andean highlanders (Figure 1). Whether this is also true for more severe cases of CMS remains unclear and a direction for future study.…”

“…Using the same approach, vascular sympathetic baroreflex function has also been explored in Peruvian Andeans of Quechan ancestry, with and without CMS (Simpson et al., 2021). Unexpectedly, vascular sympathetic baroreflex responsiveness was similar in both groups.…”

“…Moreover, Andeans with mild CMS exhibit a 20% greater total blood volume, secondary to an increased erythrocyte volume, compared to healthy Andeans (Claydon et al., 2004; Simpson et al., 2021). This greater blood volume corresponded to 25% lower MSNA, leading to a conclusion that relative sympathoinhibition in mild CMS balances haemodynamic effects of excessive erythrocytosis (i.e., elevated blood volume and blood viscosity) and maintains arterial pressure within a normal range (Simpson et al., 2021). Nevertheless, direct manipulation of blood volume is required to investigate its role in MSNA regulation in highlanders.…”

“…Furthermore, there was no change in vascular sympathetic baroreflex function (i.e., MSNA operating point, operating pressure and gain). Similarly to lowlanders, hyperoxia does not significantly influence vascular sympathetic baroreflex function in Andean highlanders nor Nepalese Sherpa, and has minimal effects upon basal MSNA at HA (Simpson et al., 2019; Simpson et al., 2021). In this study, hyperoxia duration was relatively brief, in order to eliminate peripheral chemoreceptor drive whilst minimising secondary effects of changes in CO 2 and minute ventilation.…”

Experimental Physiology special issue: Extreme environmental physiology

“…We then re‐enter Earth's atmosphere but remain at altitude, with a series of 10 papers that look at different aspects of the impact of altitude on physiology. This includes results from the 2018 Global Research Expedition to Peru examining altitude‐related chronic health (Global REACH) and comparing the physiological and pathophysiological responses of lowlanders and Andeans to exercise (Simpson et al., 2021; Tymko et al., 2021). Jiang and colleagues employ a network physiology approach to interpret the information contained in fluctuations of during normobaric hypoxia (Jiang et al., 2021).…”