Dataset Information

Global REACH: Assessment of Brady-Arrhythmias in Andeans and Lowlanders During Apnea at 4330 m.

ABSTRACT: Background: Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (i.e., 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 4330 m (Cerro de Pasco, Peru). ECG rhythm and HR were assessed at both rest and during maximal volitional apnea. 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-ventricular 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. Conclusion: 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.

SUBMITTER: Busch SA

PROVIDER: S-EPMC6987448 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Global REACH: Assessment of Brady-Arrhythmias in Andeans and Lowlanders During Apnea at 4330 m.

Busch Stephen A SA van Diepen Sean S Steele Andrew R AR Meah Victoria L VL Simpson Lydia L LL Figueroa-Mujíca Rómulo J RJ Vizcardo-Galindo Gustavo G Villafuerte Francisco C FC Tymko Michael M MM Ainslie Philip N PN Moore Jonathan P JP Stembridge Mike M Steinback Craig D CD

Frontiers in physiology 20200122

<b>Background:</b> Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (i.e., 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 arrhythmia ...[more]

PMID: 32038287

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Project description:Introduction: The cardiac electrical conduction system is very sensitive to hypoglycemia and hypoxia, and the consequence may be brady-arrythmias. Weddell seals endure brady-arrythmias during their dives when desaturating to 3.2 kPa and elite breath-hold-divers (BHD), who share metabolic and cardiovascular adaptions including bradycardia with diving mammals, endure similar desaturation during maximum apnea. We hypothesized that hypoxia causes brady-arrythmias during maximum apnea in elite BHD. Hence, this study aimed to define the arterial blood glucose (Glu), peripheral saturation (SAT), heart rhythm (HR), and mean arterial blood pressure (MAP) of elite BHD during maximum apneas. Methods: HR was monitored with Direct-Current-Pads/ECG-lead-II and MAP and Glu from a radial arterial-catheter in nine BHD performing an immersed and head-down maximal static pool apnea after three warm-up apneas. SAT was monitored with a sensor on the neck of the subjects. On a separate day, a 12-lead-ECG-monitored maximum static apnea was repeated dry (n = 6). Results: During pool apnea of maximum duration (385 ± 70 s), SAT decreased from 99.6 ± 0.5 to 58.5 ± 5.5% (∼PaO2 4.8 ± 1.5 kPa, P < 0.001), while Glu increased from 5.8 ± 0.2 to 6.2 ± 0.2 mmol/l (P = 0.009). MAP increased from 103 ± 4 to 155 ± 6 mm Hg (P < 0.005). HR decreased to 46 ± 10 from 86 ± 14 beats/minute (P < 0.001). HR and MAP were unchanged after 3-4 min of apnea. During dry apnea (378 ± 31 s), HR decreased from 55 ± 4 to 40 ± 3 beats/minute (P = 0.031). Atrioventricular dissociation and junctional rhythm were observed both during pool and dry apneas. Conclusion: Our findings contrast with previous studies concluding that Glu decreases during apnea diving. We conclude during maximum apnea in elite BHD that (1) the diving reflex is maximized after 3-4 min, (2) increasing Glu may indicate lactate metabolism in accordance with our previous results, and (3) extreme hypoxia rather than hypoglycemia causes brady-arrythmias in elite BHD similar to diving mammals.

Project description:RationaleChronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined.ObjectiveTo determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE.Methods and resultsWe tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+β adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: -52.7±19.6%, ACh2: -25.4±38.7%, ACh3: -35.1±34.7%, all P≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: -36.4%, P=0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade (P=0.012), but this effect was not observed in the EE Andeans.ConclusionsThese data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.

Project description:Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.

Project description:OBJECTIVE:Although there is anecdotal evidence of ageism occurring at both the structural level (in which societal institutions reinforce systematic bias against older persons) and individual level (in which older persons take in the negative views of aging of their culture), previous systematic reviews have not examined how both levels simultaneously influence health. Thus, the impact of ageism may be underestimated. We hypothesized that a comprehensive systematic review would reveal that these ageism levels adversely impact the health of older persons across geography, health outcomes, and time. METHOD:A literature search was performed using 14 databases with no restrictions on region, language, and publication type. The systematic search yielded 13,691 papers for screening, 638 for full review, and 422 studies for analyses. Sensitivity analyses that adjusted for sample size and study quality were conducted using standardized tools. The study protocol is registered (PROSPERO CRD42018090857). RESULTS:Ageism led to significantly worse health outcomes in 95.5% of the studies and 74.0% of the 1,159 ageism-health associations examined. The studies reported ageism effects in all 45 countries, 11 health domains, and 25 years studied, with the prevalence of significant findings increasing over time (p < .0001). A greater prevalence of significant ageism-health findings was found in less-developed countries than more-developed countries (p = .0002). Older persons who were less educated were particularly likely to experience adverse health effects of ageism. Evidence of ageism was found across the age, sex, and race/ethnicity of the targeters (i.e., persons perpetrating ageism). CONCLUSION:The current analysis which included over 7 million participants is the most comprehensive review of health consequences of ageism to date. Considering that the analysis revealed that the detrimental impact of ageism on older persons' health has been occurring simultaneously at the structural and individual level in five continents, our systematic review demonstrates the pernicious reach of ageism.

Dataset Information

Global REACH: Assessment of Brady-Arrhythmias in Andeans and Lowlanders During Apnea at 4330 m.

Publications

Global REACH: Assessment of Brady-Arrhythmias in Andeans and Lowlanders During Apnea at 4330 m.

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