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Chemoreflex Mediated Arrhythmia during Apnea at 5050m in Low but not High Altitude Natives

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P &lt; 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P &lt; 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P &lt; 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P &lt; 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P &lt; 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude. NEW &amp; NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings. </jats:p

Global REACH: Assessment of brady-arrhythmias in Andeans and Lowlanders during apnea at 4330m

BACKGROUND: Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (ie. Nepalese Sherpa) may have arrhythmias resistant adaptations that prevent arrhythmogenesis at altitude, though this has not been documented in other High altitude groups, including those diagnosed with chronic mountain sickness (CMS). We investigated whether healthy (CMS-) and CMS afflicted (CMS+) Andeans exhibit cardiac arrhythmias under acute apneic stress at altitude. METHODS AND RESULTS: Electrocardiograms (lead II) were collected in CMS- (N=9), CMS+ (N=8), and Lowlanders (N= 13) following several days at 4330m (Cerro de Pasco, Peru). ECG rhythm and HR were assessed at both rest and during maximal volitional apnea (End-Expiratory [EXP]). Both CMS- and CMS+ had similar basal HR (69 ± 8 beats/min vs. 62 ± 11 beats/min), while basal HR was higher in Lowlanders (77 ± 18 beats/min; P<0.05 versus CMS+). Apnea elicited significant bradycardia (nadir -32 ± 15 beats/min; P<0.01) and the development of arrhythmias in 8/13 Lowlanders (junctional rhythm, 3° atrio-venticular block, sinus pause). HR was preserved was prior to volitional breakpoint in both CMS- (nadir -6 ± 1 beat/min) and CMS+ (1 ±12 beats/min), with 2/17 Andeans developing arrhythmias ( 1 CMS+ and 1 CMS-; both Premature Atrial Contraction) prior to breakpoint. CONCLUSIONS: Andeans showed an absence of arrhythmias and preserved HR response to volitional apnea at altitude, demonstrating that potential cardio-resistant adaptations to arrhythmogenesis exist across permanent HA populations. Acclimatized Lowlanders have further demonstrated an increased prevalence of arrhythmias at altitude

Muscle sympathetic reactivity to apneic and exercise stress in high-altitude Sherpa

Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that may alter vascular function. High altitude populations, such as Sherpa, exhibit greater peripheral blood flow in response to acute stress, suggesting Sherpas may exhibit lower sympathetic activity and reactivity to stress than Lowlanders. Muscle sympathetic activity (MSNA; microneurography) including frequency (bursts/min), incidence (bursts/100HB), amplitude (% of max burst), was measured at rest in Lowlanders (n=14; age=27±6yrs) at 344m and following a 8- 9 days of graded ascent to 5050m. Sherpa (age=32±11yrs) were tested at 5050m (n=8). Neurovascular reactivity (i.e., change in MSNA patterns) was measured during maximal end expiratory apnea, isometric hand-grip (IHG; 30% maximal voluntary contraction for 2 minutes) and post exercise circulatory occlusion (PECO; 3 minutes). Total normalized SNA (au/min) was calculated over 10 cardiac cycles during baseline and pre-volitional apnea breakpoint. Lowlander burst frequency (11±5 bursts/min to 30±7 bursts/min; Mean±SD; p<0.001) and burst incidence (25±13 bursts/100HB to 53±15 bursts/100HB; p<0.001) increased at 5050m. In contrast, Sherpas had lower burst frequency (23±11 bursts/min; p<0.05) and incidence (30±13 bursts/100HB; p<0.05) at 5050m. MSNA increases in Lowlanders and Sherpa during apnea at 5050m were significantly lower than Lowlanders at 344m (both P<0.05), with a possible sympathetic ceiling reached in Lowlanders at 5050m. MSNA increased similarly during the IHG/PECO in Lowlanders at 334m and 5050m altitude and Sherpa at 5050m. Sherpa demonstrate overall lower sympathetic activity and reactivity during severe stress. This may be a result of improved systemic hemodynamic function associated with evolutionary adaptations to permanent residency at altitude

UBC-Nepal Expedition: An experimental overview of the 2016 University of British Columbia Scientific Expedition to Nepal Himalaya

The University of British Columbia Nepal Expedition took place over several months in the fall of 2016 and was comprised of an international team of 37 researchers. This paper describes the objectives, study characteristics, organization and management of this expedition, and presents novel blood gas data during acclimatization in both lowlanders and Sherpa. An overview and framework for the forthcoming publications is provided. The expedition conducted 17 major studies with two principal goals—to identify physiological differences in: 1) acclimatization; and 2) responses to sustained high-altitude exposure between lowland natives and people of Tibetan descent. We performed observational cohort studies of human responses to progressive hypobaric hypoxia (during ascent), and to sustained exposure to 5050 m over 3 weeks comparing lowlander adults (n = 30) with Sherpa adults (n = 24). Sherpa were tested both with (n = 12) and without (n = 12) descent to Kathmandu. Data collected from lowlander children (n = 30) in Canada were compared with those collected from Sherpa children (n = 57; 3400–3900m). Studies were conducted in Canada (344m) and the following locations in Nepal: Kathmandu (1400m), Namche Bazaar (3440m), Kunde Hospital (3480m), Pheriche (4371m) and the Ev-K2-CNR Research Pyramid Laboratory (5050m). The core studies focused on the mechanisms of cerebral blood flow regulation, the role of iron in cardiopulmonary regulation, pulmonary pressures, intra-ocular pressures, cardiac function, neuromuscular fatigue and function, blood volume regulation, autonomic control, and micro and macro vascular function. A total of 335 study sessions were conducted over three weeks at 5050m. In addition to an overview of this expedition and arterial blood gas data from Sherpa, suggestions for scientists aiming to perform field-based altitude research are also presented. Together, these findings will contribute to our understanding of human acclimatization and adaptation to the stress of residence at high-altitude