Centro de Fisiología y Medicina de Altura

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Baroreflex and chemoreflex interaction in high-altitude exposure: possible role on exercise performance
(Frontiers Media SA, 2024) Alvarez Araos, Pablo; Jiménez, Sergio; Salazar Ardiles, Camila; Núñez Espinosa, Cristian; Paez, Valeria; Rodriguez Fernandez, Maria; Raberin, Antoine; Millet, Gregoire P.; Iturriaga, Rodrigo; Andrade, David C.
The hypoxic chemoreflex and the arterial baroreflex are implicated in the ventilatory response to exercise. It is well known that long-term exercise training increases parasympathetic and decreases sympathetic tone, both processes influenced by the arterial baroreflex and hypoxic chemoreflex function. Hypobaric hypoxia (i.e., high altitude [HA]) markedly reduces exercise capacity associated with autonomic reflexes. Indeed, a reduced exercise capacity has been found, paralleled by a baroreflex-related parasympathetic withdrawal and a pronounced chemoreflex potentiation. Additionally, it is well known that the baroreflex and chemoreflex interact, and during activation by hypoxia, the chemoreflex is predominant over the baroreflex. Thus, the baroreflex function impairment may likely facilitate the exercise deterioration through the reduction of parasympathetic tone following acute HA exposure, secondary to the chemoreflex activation. Therefore, the main goal of this review is to describe the main physiological mechanisms controlling baro- and chemoreflex function and their role in exercise capacity during HA exposure.
Consequences of Exposure to Hypobaric Hypoxia Associated with High Altitude on Spermatogenesis and Seminal Parameters: A Literature Review
(MDPI, 2024) Cornejo Guerra, Carlos; Salazar Ardiles, Camila; Morales, Patricio; Andrade, David C.
Preclinical research has provided compelling evidence indicating that exposure to hypobaric hypoxia (HH) results in a deterioration of spermatogenesis. This adverse effect extends to the underlying molecular mechanisms, progressively leading to impairments in the seminiferous epithelium and germ cells and alterations in semen parameters. Indeed, several studies have demonstrated that animals exposed to HH, whether in natural high-altitude environments or under simulated hypoxic conditions, exhibit damage to the self-renewal and differentiation of spermatogenesis, an increase in germline cell apoptosis, and structural alterations in the seminiferous tubules. One of the primary mechanisms associated with the inhibition of differentiation and an increase in apoptosis among germ cells is an elevated level of oxidative stress, which has been closely associated with HH exposure. Human studies have shown that individuals exposed to HH, such as mountaineers and alpinists, exhibit decreased sperm count, reduced motility, diminished viability, and increased sperm with abnormal morphology in their semen. This evidence strongly suggests that exposure to HH may be considered a significant risk factor that could elevate the prevalence of male infertility. This literature review aims to provide a comprehensive description and propose potential mechanisms that could elucidate the infertility processes induced by HH. By doing so, it contributes to expanding our understanding of the challenges posed by extreme environments on human physiology, opening new avenues for research in this field.
Deep Learning-Based Glucose Prediction Models: A Guide for Practitioners and a Curated Dataset for Improved Diabetes Management
(Institute of Electrical and Electronics Engineers Inc., 2024) Langarica, Saúl; de la Vega, Diego; Cariman, Nawel; Miranda, Martín; Andrade, David C.; Núñez, Felipe; Rodriguez-Fernandez, Maria
Accurate short- and mid-term blood glucose predictions are crucial for patients with diabetes struggling to maintain healthy glucose levels, as well as for individuals at risk of developing the disease. Consequently, numerous efforts from the scientific community have focused on developing predictive models for glucose levels. This study harnesses physiological data collected from wearable sensors to construct a series of data-driven models based on deep learning approaches. We systematically compare these models to offer insights for practitioners and researchers venturing into glucose prediction using deep learning techniques. Key questions addressed in this work encompass the comparison of various deep learning architectures for this task, determining the optimal set of input variables for accurate glucose prediction, comparing population-wide, fine-tuned, and personalized models, and assessing the impact of an individual’s data volume on model performance. Additionally, as part of our outcomes, we introduce a meticulously curated dataset inclusive of data from both healthy individuals and those with diabetes, recorded in free-living conditions. This dataset aims to foster research in this domain and facilitate equitable comparisons among researchers.
Detraining’s Effects on Cardiorespiratory Fitness and Maximal and Explosive Strength in Army Soldiers: Does Age Matter?
(MDPI, 2024) Arce-Álvarez, Alexis; Zaio, Ángelo; Salazar Ardiles, Camila; Álvarez, Cristian; Merino Muñoz, Pablo; Vasquez-Muñoz, Manuel; Izquierdo, Mikel; Castro, Mauricio; Andrade, David C.
Purpose: This study investigated the impact of four weeks of age-dependent detraining on army soldiers’ cardiorespiratory fitness and maximal and explosive strength. Methods: Fourteen volunteer tactical athletes participated, divided into two age groups (20 to 29 and 30 to 40 years). Before and after the detraining period, we assessed their anthropometric measurements (weight, height, body mass index, fat mass, and fat-free mass), cardiorespiratory fitness (maximal oxygen uptake [VO2max] and ventilatory thresholds [VT1 and VT2]), and kinematic properties during a single-leg counter-moving jump (CMJ) test for both the dominant and non-dominant legs. Two-way ANOVA followed by the Holm–Sidak post hoc test was used. Results: The anthropometric and cardiovascular variables did not show significant differences between the groups. However, both groups exhibited a significantly reduced maximum time and speed at the VO2max. Furthermore, the flight time and maximum height during the CMJ significantly decreased in the non-dominant leg for both age groups. Notably, the dominant leg’s concentric impulse (CI) significantly reduced during the CMJ, but this effect was observed only in the 30–40 age group. There were significant differences between the two age groups. Conclusions: Our findings suggest that four weeks of detraining negatively impacts aerobic fitness and muscular strength, independently of age. However, the dominant leg may be more susceptible to detraining effects in army soldiers aged 30–40. Furthermore, as a perspective, our results strongly suggest that a detraining period could affect successful missions (aerobic performance deterioration), as well as promote a muscle imbalance between the legs, which could encourage muscle injuries and endanger combat missions.
Dietary supplementation of a sulforaphane-enriched broccoli extract protects the heart from acute cardiac stress
(ELSEVIER, 2020) Pereyra, Katherin V.; Andrade, David C.; Toledo, Camilo; Schwarz, Karla G.; Uribe-Ojeda, Atenea; Ríos-Gallardo, Angélica P.; Quintanilla, Rodrigo A.; Contreras, Samuel; Mahn, Andrea; Del Rio, Rodrigo
Cardiac arrythmias play a critical role in several pathological conditions. Importantly, increased arrhythmic risk is associated with systemic oxidative stress and activation of the autonomic nervous system. Thus, we hypothesized that dietary antioxidant supplementation may help in reducing cardiac stress-induced arrhythmias. Sulforaphane (SFN), an isothiocyanate present in Brassicaceaes, is recognized as a powerful health-promoting compound with known antioxidant properties. Then, we aimed to generate a broccoli extract (BE) enriched in SFN and determine whether oral BE supplementation induced cardio-protection during acute cardiac stress in rats. BE decreases cardiac sympathetic drive and increases parasympathetic cardiac modulation as evidenced by heart rate variability (HRV) shifts. In addition, isoproterenol-induced cardiac stress (a sympathomimetic agent) induced a ~ 4-fold increase in arrhythmia incidence and this effect was almost completely abolished by BE treatment. In conclusion, dietary supplementation with a BE regulates cardiac autonomic drive and protects the heart from acute cardiac stress.
Effects of enriched‑potassium diet on cardiorespiratory outcomes in experimental non‑ischemic chronic heart failure
(BMC, 2021) Schwarz, Karla G.; Pereyra, Katherin V.; Toledo, Camilo; Andrade, David C.; Díaz, Hugo S.; Díaz‑Jara, Esteban; Ortolani, Domiziana; Rios‑Gallardo, Angélica; Arias, Paulina; Las Heras, Alexandra; Vera, Ignacio; Ortiz, Fernando C.; Inestrosa, Nibaldo C.; Vio, Carlos P.; Del Rio, Rodrigo
Background: Chronic heart failure (CHF) is a global health problem. Increased sympathetic outflow, cardiac arrhythmogenesis and irregular breathing patterns have all been associated with poor outcomes in CHF. Several studies showed that activation of the renin-angiotensin system (RAS) play a key role in CHF pathophysiology. Interestingly, potassium (K+) supplemented diets showed promising results in normalizing RAS axis and autonomic dysfunction in vascular diseases, lowering cardiovascular risk. Whether subtle increases in dietary K+ consumption may exert similar effects in CHF has not been previously tested. Accordingly, we aimed to evaluate the effects of dietary K+ supplementation on cardiorespiratory alterations in rats with CHF. Methods: Adult male Sprague–Dawley rats underwent volume overload to induce non-ischemic CHF. Animals were randomly allocated to normal chow diet (CHF group) or supplemented K+ diet (CHF+K+ group) for 6 weeks. Cardiac arrhythmogenesis, sympathetic outflow, baroreflex sensitivity, breathing disorders, chemoreflex function, respiratory–cardiovascular coupling and cardiac function were evaluated. Results: Compared to normal chow diet, K+supplemented diet in CHF significantly reduced arrhythmia incidence (67.8 ± 15.1 vs. 31.0 ± 3.7 events/hour, CHF vs. CHF+K+), decreased cardiac sympathetic tone (ΔHR to propranolol:− 97.4 ± 9.4 vs. − 60.8 ± 8.3 bpm, CHF vs. CHF+K+), restored baroreflex function and attenuated irregular breathing patterns. Additionally, supplementation of the diet with K+ restores normal central respiratory chemoreflex drive and brogates pathological cardio-respiratory coupling in CHF rats being the outcome an improved cardiac function. Conclusion: Our findings support that dietary K+ supplementation in non-ischemic CHF alleviate cardiorespiratory dysfunction.
Exercise intolerance in volume overload heart failure is associated with low carotid body mediated chemoreflex drive
(Nature Research, 2021) Andrade, David C.; Díaz‑Jara, Esteban; Toledo, Camilo; Schwarz, Karla G.; Pereyra, Katherin V.; Díaz, Hugo S.; Marcus, Noah J.; Ortiz, Fernando C.; Ríos‑Gallardo, Angélica P.; Ortolani, Domiziana; Del Rio, Rodrigo
Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands, and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in heart failure (HF) patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses, and exercise tolerance were assessed at the end of a 6 week exercise training program. At the conclusion of the training program, exercise tolerant HF rats (HF + EX-T) exhibited improvements in cardiac systolic function and reductions in HCVR, sympathetic tone, and arrhythmias. In contrast, HF rats that were exercise intolerant (HF + EX-inT) exhibited worse diastolic dysfunction, and showed no improvements in cardiac systolic function, HCVR, sympathetic tone, or arrhythmias at the conclusion of the training program. In addition, HF + EX-inT rats had impaired HVR which was associated with increased arrhythmia susceptibility and mortality during hypoxic challenges (~ 60% survival). Finally, we observed that exercise tolerance in HF rats was related to carotid body (CB) function as CB ablation resulted in impaired exercise capacity in HF + EX-T rats. Our results indicate that: (i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and (ii) loss of CB chemoreflex sensitivity contributes to EX-inT in HF.
Heart rate and cardiac autonomic responses to concomitant deep breathing, hand grip exercise, and circulatory occlusion in healthy young adult men and women
(BMC, 2021) Andrade, David C.; Melipillan, Claudia; Toledo, Camilo; Rios Gallardo, Angélica; Marcus, Noah J.; Ortiz, Fernando C.; Martinez, Gonzalo; Muñoz Venturelli, Paula; Del Rio, Rodrigo
Background: Deep breathing (DB) and handgrip (HG) exercise -with and without circulatory occlusion (OC) in muscle-, have been shown to have beneficial effects on cardiovascular function; however, the combination of these maneuvers on heart rate (HR) and cardiac sympathovagal balance have not been previously investigated. Therefore, the aim of the present study was to evaluate the effect of simultaneous DB, HG, and OC maneuvers on the sympathovagal balance in healthy women and men subjects. Methods and results: Electrocardiogram and ventilation were measured in 20 healthy subjects (Women: n = 10; age = 27 ± 4 years; weight = 67.1 ± 8.4 kg; and height = 1.6 ± 0.1 m. Men: n = 10; age = 27 ± 3 years; weight = 77.5 ± 10.1 kg; and height = 1.7 ± 0.1 m) at baseline and during DB, DB + HG, or DB + HG + OC protocols. Heart rate (HR) and respiratory rate were continuously recorded, and spectral analysis of heart rate variability (HRV) were calculated to indirectly estimate cardiac autonomic function. Men and women showed similar HR responses to DB, DB + HG and DB + HG + OC. Men exhibited a significant HR decrease following DB + HG + OC protocol which was accompanied by an improvement in cardiac autonomic control evidenced by spectral changes in HRV towards parasympathetic predominance (HRV High frequency: 83.95 ± 1.45 vs. 81.87 ± 1.50 n.u., DB + HG + OC vs. baseline; p < 0.05). In women, there was a marked decrease in HR after completion of both DB + HG and DB + HG + OC tests which was accompanied by a significant increase in cardiac vagal tone (HRV High frequency: 85.29 ± 1.19 vs. 77.93 ± 0.92 n.u., DB + HG vs. baseline; p < 0.05). No adverse effects or discomfort were reported by men or women during experimental procedures. Independent of sex, combination of DB, HG, and OC was tolerable and resulted in decreases in resting HR and elevations in cardiac parasympathetic tone. Conclusions: These data indicate that combined DB, HG and OC are effective in altering cardiac sympathovagal balance and reducing resting HR in healthy men and women.
Hypoxic peripheral chemoreflex stimulation- dependent cardiorespiratory coupling is decreased in swimmer athletes
(John Wiley & Sons Inc., 2024) Andrade, David C.; Arce Álvarez, Alexis; Salazar Ardiles, Camila; Toledo, Camilo; Guerrero Henriquez, Juan; Alvarez, Cristian; Vasquez Muñoz, Manuel; Izquierdo, Mikel; Millet, Gregoire P.
Swimmer athletes showed a decreased ventilatory response and reduced sympathetic activation during peripheral hypoxic chemoreflex stimulation. Based on these observations, we hypothesized that swimmers develop a diminished cardiorespiratory coupling due to their decreased hypoxic peripheral response. To resolve this hypothesis, we conducted a study using coherence time- varying analysis to assess the cardiorespiratory coupling in swimmer athletes. We recruited 12 trained swimmers and 12 control subjects for our research. We employed wavelet time- varying spectral coherence analysis to examine the relationship between the respiratory frequency (Rf) and the heart rate (HR) time series during normoxia and acute chemoreflex activation induced by five consecutive inhalations of 100% N2. Comparing swimmers to control subjects, we observed a significant reduction in the hypoxic ventilatory responses to N2 in swimmers (0.012 ± 0.001 vs. 0.015 ± 0.001 ΔVE/ΔVO2, and 0.365 ± 0.266 vs. 1.430 ± 0.961 ΔVE/ΔVCO2/ΔSpO2, both p < 0.001, swimmers vs. control, respectively). Furthermore, the coherence at the LF cutoff during hypoxia was significantly lower in swimmers compared to control subjects (20.118 ± 3.502 vs. 24.935 ± 3.832 area under curve [AUC], p < 0.012, respectively). Our findings strongly indicate that due to their diminished chemoreflex control, swimmers exhibited a substantial decrease in cardiorespiratory coupling during hypoxic stimulation.
Hypoxic Respiratory Chemoreflex Control in Young Trained Swimmers
(Frontiers Media SA, 2021) Arce Álvarez, Alexis; Veliz, Carlos; Vazquez-Muñoz, Manuel; von Igel, Magdalena; Alvares, Cristian; Ramirez Campillo, Rodrigo; Izquierdo, Mikel; Millet, Gregoire P.; Del Rio, Rodrigo; Andrade, David C.
During an apnea, changes in PaO2 activate peripheral chemoreceptors to increase respiratory drive. Athletes with continuous apnea, such as breath-hold divers, have shown a decrease in hypoxic ventilatory response (HVR), which could explain the long apnea times; however, this has not been studied in swimmers. We hypothesize that the long periods of voluntary apnea in swimmers is related to a decreased HVR. Therefore, we sought to determine the HVR and cardiovascular adjustments during a maximum voluntary apnea in young-trained swimmers. In fifteen trained swimmers and twentyseven controls we studied minute ventilation (VE), arterial saturation (SpO2), heart rate (HR), and autonomic response [through heart rate variability (HRV) analysis], during acute chemoreflex activation (five inhalations of pure N2) and maximum voluntary apnea test. In apnea tests, the maximum voluntary apnea time and the end-apnea HR were higher in swimmers than in controls (p < 0.05), as well as a higher low frequency component of HRV (p < 0.05), than controls. Swimmers showed lower HVR than controls (p < 0.01) without differences in cardiac hypoxic response (CHR). We conclude that swimmers had a reduced HVR response and greater maximal voluntary apnea duration, probably due to decreased HVR.
Peripheral chemoreceptor, a new player in metabolic sensing during physical exertion: a hypothetical scenario
(American Physiological Society, 2025) Andrade, David C.
The cardiorespiratory and metabolic response to exercise has been associated with meeting the organism’s metabolic demands during physical exertion. Of note, an incremental exercise is characterized by 1) cardiodynamic phase related to cardiac output enhancement mainly determined by a positive chronotropic response, 2) ventilatory threshold one, associated with a significant contribution of cardiovascular and pulmonary ventilation, and 3) ventilatory threshold two, correlated with a tremendous increase in breathing and metabolic responses to exercise. Notably, it has been shown that the ventilatory response to exercise increases concomitantly with the release and accumulation of metabolites (i.e., lactate released from skeletal muscle). The principal peripheral chemoreceptors are the carotid bodies (CBs), allocated into the carotid bifurcation and demonstrated to respond to several stimuli, triggering autonomic and ventilatory responses. Indeed, in past and recent years, it has been shown that CB could respond to lactate in in vitro and in vivo preparations, eliciting an increase in CB activity and ventilation. However, not all evidence indicates that peripheral chemoreceptors respond to lactate. Thus, considering that CB chemoreceptors’ role in lactatedependent breathing response is not completely clear and their potential preponderance as metabolic sensors during exercise has not been thoroughly explored, the present review was focused on the possible role of CB chemoreceptors as metabolic sensors during physical exertion in a physiological context, proposing it as a new actor in exercise physiology
Uncovering Hidden Microbial Diversity in Nitrate/Iodide Deposits (NIDs) in the Domeyko District, Atacama Desert, Chile
(MDPI, 2024) Cortés, Mayra; Avendaño, Priscilla; Encalada, Olga; Salazar Ardiles, Camila; Andrade, David C.; Gómez Silva, Benito; Contreras, Daniel; Toro, Norman; Arias, Dayana; Escudero, Lorena V.
Unique worldwide, nitrate/iodine deposits (NIDs) are located along a 700 km geological belt in the Atacama Desert, Chile. They serve as the primary source of mineral ores for the extraction of iodine, sodium, and potassium nitrates. NIDs have been relatively underexplored from a biological perspective. To address this, we collected sixteen soil samples from abandoned mines in Oficinas Pissis and Savona for chemical, mineralogical, and metagenomic analyses. The soils primarily consisted of halite and darapskite, with only one sample being predominantly composed of thenardite. Deliquescence and water activity measurements yielded values ranging from 0.02% to 0.40% and 0.47 to 0.62, respectively. To investigate the presence, identification, relative abundance, and diversity of microbial life in NID soils, we employed MiSeq high-throughput sequencing and bioinformatic tools. The dominant phyla observed were Firmicutes and Proteobacteria, with Actinobacteria and Cyanobacteria being predominant in two soil samples. Furthermore, we detected nitrate/perchloratereducing bacterial activity in enriched cultures from the soil samples. This study sheds light on the resilience of microbial life in the Atacama Desert NIDs, providing compelling evidence for its existence and offering insight into factors that could facilitate it within this unique environment.

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