Parasympathetic withdrawal increases heart rate after 2 weeks at 3454 m altitude

Abstract

Chronic hypoxia increases resting heart rate (HR), but the underlying mechanism remains incompletely understood. We investigated the relative contributions of the sympathetic and parasympathetic nervous systems, along with potential non-autonomic mechanisms, by individual and combined pharmacological inhibition of muscarinic and/or β-adrenergic receptors. In seven healthy lowlanders, resting HR was determined at sea level (SL) and after 15-18 days of exposure to 3454 m high altitude (HA) without drug intervention (control, CONT) as well as after intravenous administration of either propranolol (PROP), or glycopyrrolate (GLYC), or PROP and GLYC in combination (PROP+GLYC). Circulating noradrenaline concentration increased from 0.9 ± 0.4 nmol l at SL to 2.7 ± 1.5 nmol l at HA (P = 0.03). The effect of HA on HR depended on the type of autonomic inhibition (P = 0.006). Specifically, HR was increased at HA from 64 ± 10 to 74 ± 12 beats min during the CONT treatment (P = 0.007) and from 52 ± 4 to 59 ± 5 beats min during the PROP treatment (P < 0.001). In contrast, HR was similar between SL and HA during the GLYC treatment (110 ± 7 and 112 ± 5 beats min , P = 0.28) and PROP+GLYC treatment (83 ± 5 and 85 ± 5 beats min , P = 0.25). Our results identify a reduction in cardiac parasympathetic activity as the primary mechanism underlying the elevated HR associated with 2 weeks of exposure to hypoxia. Unexpectedly, the sympathoactivation at HA that was evidenced by increased circulating noradrenaline concentration had little effect on HR, potentially reflecting down-regulation of cardiac β-adrenergic receptor function in chronic hypoxia. These effects of chronic hypoxia on autonomic control of the heart may concern not only HA dwellers, but also patients with disorders that are associated with hypoxaemia.

Recruitment of non‐perfused sublingual capillaries increases microcirculatory oxygen extraction capacity throughout ascent to 7126 m

“…The increase in resting heart rate during exposure to 6022 m and 7042 m, as observed in the present study, corresponds with previous data (Lundby & van Hall, ) and has been attributed mostly to high altitude‐related sympathoexcitation and parasympathetic withdrawal (Siebenmann et al . ). Cardiac output at rest is expected to decrease towards SL values after an initial increase in well‐acclimatized lowlanders at moderate altitude (Hilty et al .…”

Baroreflex Modulation During Acute High-Altitude Exposure in Rats

“…Accordingly, Obrezchikova et al (2000) also showed that during hypoxic challenges (hypobaric hypoxic chamber), the parasympathetic modulation is decreased in conscious freely moving rats. Similarly, it has been shown that chronic exposure to High-Altitude, causes increases in HR due to parasympathetic withdrawal ( Dhar et al, 2014 ; Siebenmann et al, 2017 ). Something interesting to note, is that the parasympathetic withdrawal could persist after one month of high-altitude exposure ( Farinelli et al, 1994 ; Dhar et al, 2014 ).…”

Lifelong high‐altitude hypoxia induces arterial baroreflex adaptations: new insights and future directions

“…Additionally, in contrast to baroreflex control of MSNA, cardiac baroreflex sensitivity is closely related to vagal activity, and increases in resting heart rate at HA are proposed to be mediated by cardiac vagal withdrawal with minimal or no effect of sympathetic activity (Siebenmann et al . ). Furthermore, as the authors mentioned, erythropoietin production, systemic inflammation and oxidative stress could also explain the study findings.…”