Highs and Lows of Sympathetic Neuro-cardiovascular Transduction: Influence of Altitude Acclimatization and Adaptation

High-altitude (>2500m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in 66 indigenous high-altitude populations. Additionally, the relationship between MSNA and blood 67 pressure regulation (i.e., neurovascular transduction) at high-altitude is unclear. We sought to 68 determine 1) how high-altitude effects neuro-cardiovascular transduction and 2) whether 69 differences exist in neuro-cardiovascular transduction between low and high-altitude 70 populations. Measurements of MSNA (microneurography), mean arterial blood pressure (MAP; 71 finger photoplethysmography), and heart rate (electrocardiogram) were collected in: I) 72 lowlanders (n=14) at low (344m) and high-altitude (5050m), II) Sherpa highlanders (n=8; 73 5050m), and III) Andean (with and without excessive erythrocytosis) highlanders (n=15; 74 4300m). Cardiovascular responses to MSNA burst sequences (i.e. singlet, couplet, triplet, and 75 quadruplets) were quantified using custom software (coded in MATLAB, v2015b). Slopes were 76 generated for each individual based on peak responses and normalized total MSNA. High 77 altitude reduced neuro-cardiovascular transduction in lowlanders (MAP slope: high-altitude, 78 0.0075±0.0060 vs low-altitude, 0.0134±0.080; p=0.03). Transduction was elevated in Sherpa 79 (MAP slope, 0.012±0.007) compared to Andeans (0.003±0.002; p=0.001). MAP transduction 80 was not statistically different between acclimatizing lowlanders and Sherpa (MAP slope, p=0.08) 81 or Andeans (MAP slope, p=0.07). When accounting for resting MSNA (ANCOVA), transduction 82 was inversely related to basal MSNA (bursts/min) independent of population (RRI, r= 0.578 83 p<0.001; MAP, r= -0.627 p<0.0001). Our results demonstrate transduction is blunted in 84 individuals with higher basal MSNA, suggesting blunted neuro-cardiovascular transduction is a 85 physiological adaptation to elevated MSNA rather than an effect or adaptation specific to 86 chronic hypoxic exposure

Global REACH 2018: Andean Highlanders, Chronic Mountain Sickness and the Integrative Regulation of Resting Blood Pressure

High‐altitude maladaptation syndrome chronic mountain sickness (CMS) is characterised by excessive erythrocytosis and frequently accompanied by accentuated arterial hypoxaemia. Whether altered autonomic cardiovascular regulation is apparent in CMS is unclear. Therefore, we assessed integrative control of blood pressure (BP) and determined basal sympathetic vasomotor outflow and arterial baroreflex function in 8 Andean natives with CMS ([Hb] 22.6 ± 0.9 g/dL) and 7 healthy highlanders ([Hb] 19.3 ± 0.8 g/dL) at their resident altitude (Cerro de Pasco, Peru; 4383 m). 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 ± 0.7cP; 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 ± 50msec; d = 1.4, P = 0.04) with a greater reflex gain (17.2 ± 6.8 vs 8.8 ± 2.6msec·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 ± 13bursts·min−1; d = 1.0, P = 0.08). In conclusion, our findings indicate adaptive differences in basal sympathetic vasomotor activity and heart rate compensate for the haemodynamic consequences of excessive erythrocyte volume and contribute to integrative blood pressure regulation in Andean highlanders with mild CMS

The 2018 Global Research Expedition on Altitude-related Chronic Health (REACH) to Cerro de Pasco, Peru: An Experimental Overview

In 2016, the international research team - Global Research Expedition onAltitude-related Chronic Health (REACH) - was established and executed a high altituderesearch expedition to Nepal. The team consists of ~45 students, principal investigatorsand physicians with the common objective of conducting experiments focused on highaltitude adaptation in lowlanders, and highlanders with lifelong exposure to high altitude.In 2018, Global REACH traveled to Peru where we performed a series of experiments inthe Andean highlanders. The experimental objectives, organization and characteristics,and key cohort data from Global REACH's latest research expedition are outlined herein.Herein, fifteen major studies are described that aimed to elucidate the physiologicaldifferences in high altitude acclimatization between lowlanders (n=30) and Andean bornhighlanders with (n=22) and without (n=45) Excessive Erythrocytosis (EE). Afterbaseline testing in Kelowna, BC, Canada (344m), Global REACH travelled to Lima, Peru(~80 m), and then ascended by automobile to Cerro de Pasco, Peru (~4300m) whereexperiments were conducted over 25 days. The core studies focused on elucidating themechanism(s) governing cerebral and peripheral vascular function, cardiopulmonaryregulation, exercise performance, and autonomic control. Despite encountering seriouslogistical challenges, each of the proposed studies were completed at both sea level andhigh altitude amounting to ~780 study sessions and >3000 hrs of experimental testing.Participant demographics and data related to acid-base balance and exercise capacityare presented. The collective findings will contribute to our understanding of howlowlanders and Andean highlanders have adapted under high altitude stress

High altitudes, population density, and poverty: Unraveling the complexities of COVID-19 in Peru during the years 2020–2022

Background: Several factors related to hospitalizations, morbidity, and mortality from COVID-19 have been identified. However, limited exploration has been done on geographic and socioeconomic factors that could significantly impact these outcomes. Objectives: This study aimed to determine whether altitude, population density, and percentage of population in total poverty are associated with COVID-19 incidence per 1000 inhabitants and COVID-19 case-fatality rate in Peru, from 2020 to 2022. Methods: This study utilized a multiple group ecological design and relied on secondary databases containing daily records of COVID-19 positive cases and deaths due to COVID-19. An epidemiological analysis was performed, subsequently processed using a random effects model. Results: As of August 2022, Peru had recorded a total of 3,838,028 COVID-19 positive cases and 215,023 deaths due to COVID-19. Our analysis revealed a statistically significant negative association between altitude and COVID-19 incidence (aBETA: −0.004; Standard Error: 0.001; p < 0.05). Moreover, we observed a positive association between population density and incidence (aBETA: 0.006; Standard Error: 0.001; p < 0.05). However, we found no significant association between the percentage of population in total poverty and COVID-19 incidence. Conclusion: Our study found that an increase in altitude was associated with a decrease in COVID-19 incidence, while an increase in population density was associated with an increase in COVID-19 incidence. High altitude, population density and percentage of population in total poverty does not change case-fatality rate due to COVID-19

Sociodemographic Predictors Associated with the Willingness to Get Vaccinated against COVID-19 in Peru: A Cross-Sectional Survey

During the race for the development of a vaccine against COVID-19, even before its commercialization, part of the population has already shown a growing fear of its application. We designed an analytical cross-sectional study using an anonymous survey in the 25 departments of Peru. We surveyed whether the participants were planning on getting vaccinated, as well as other characteristics that were cross-checked in a uni-, bi- and multivariate manner. Of the 1776 respondents, 70% (1251) stated that they were planning to be vaccinated, 20% (346) did not know yet or doubted it, and 10% (179) did not want to be vaccinated. We observed that those who did not get infected with COVID-19 exhibited a higher frequency to not wanting or were uncertain about getting vaccinated (aPR: 1.40; 95% CI: 1.09&ndash;1.81; p-value = 0.008). In contrast, there was a lower frequency of vaccine refusal among university students (aPR: 0.75; 95% CI: 0.61&ndash;0.92; p-value = 0.005) and healthcare workers (aPR: 0.59; 95% CI: 0.44&ndash;0.80; p-value = 0.001); adjusted by place of residence. There is still an important percentage of respondents who do not want to be vaccinated or are hesitant to do it, which was associated with educational level, being a healthcare worker and if they were previously infected with COVID-19. Our results could offer useful information about COVID-19 vaccination campaigns