A cross-sectional study of differences in 6-min walk distance in healthy adults residing at high altitude versus sea level

BACKGROUND: We sought to determine if adult residents living at high altitude have developed sufficient adaptation to a hypoxic environment to match the functional capacity of a similar population at sea level. To test this hypothesis, we compared the 6-min walk test distance (6MWD) in 334 residents living at sea level vs. at high altitude. METHODS: We enrolled 168 healthy adults aged ≥35 years residing at sea level in Lima and 166 individuals residing at 3,825 m above sea level in Puno, Peru. Participants completed a 6-min walk test, answered a sociodemographics and clinical questionnaire, underwent spirometry, and a blood test. RESULTS: Average age was 54.0 vs. 53.8 years, 48% vs. 43% were male, average height was 155 vs. 158 cm, average blood oxygen saturation was 98% vs. 90%, and average resting heart rate was 67 vs. 72 beats/min in Lima vs. Puno. In multivariable regression, participants in Puno walked 47.6 m less (95% CI -81.7 to -13.6 m; p < 0.01) than those in Lima. Other variables besides age and height that were associated with 6MWD include change in heart rate (4.0 m per beats/min increase above resting heart rate; p < 0.001) and percent body fat (-1.4 m per % increase; p = 0.02). CONCLUSIONS: The 6-min walk test predicted a lowered functional capacity among Andean high altitude vs. sea level natives at their altitude of residence, which could be explained by an incomplete adaptation or a protective mechanism favoring neuro- and cardioprotection over psychomotor activity

Developing capacity in health informatics in a resource poor setting: lessons from Peru

The public sectors of developing countries require strengthened capacity in health informatics. In Peru, where formal university graduate degrees in biomedical and health informatics were lacking until recently, the AMAUTA Global Informatics Research and Training Program has provided research and training for health professionals in the region since 1999. The Fogarty International Center supports the program as a collaborative partnership between Universidad Peruana Cayetano Heredia in Peru and the University of Washington in the United States of America. The program aims to train core professionals in health informatics and to strengthen the health information resource capabilities and accessibility in Peru. The program has achieved considerable success in the development and institutionalization of informatics research and training programs in Peru. Projects supported by this program are leading to the development of sustainable training opportunities for informatics and eight of ten Peruvian fellows trained at the University of Washington are now developing informatics programs and an information infrastructure in Peru. In 2007, Universidad Peruana Cayetano Heredia started offering the first graduate diploma program in biomedical informatics in Peru

Mal de montaña crónico entre mineros de Cerro de Pasco: Evidencias epidemiológicas y fisiológicas.

Hace cien mil años Viault (1890) demostró un aumento en el número de glóbulos rojos de personas que vivían en Morococha a 4,500 metros sobre el nivel del mar. Desde entonces se empezó a desarrollar el concepto de adaptación a las grandes alturas. Estudios posteriores demostraron que efectivamente el nativo de altura lograba aclimatarse a su ambiente con poco oxígeno pero que eventualmente podía perder esta adaptación. La descripción del primer caso de Mal de Montaña Crónico (MMC) hecha por Monge M. En 1928 dio lugar a la aparición del concepto de desadaptación a las grandes alturas

Autonomic adaptations in Andean trained participants to a 4220-m altitude marathon

Purpose: Both training and chronic hypoxia act on the autonomic nervous system. Because trained Andean high-altitude natives could perform a high-altitude marathon (4220 m above sea level) in 02:27:23 h, we hypothesized that living in chronic hypoxia does not limit the training-induced benefits on the autonomic modulation of the heart. Methods: Trained (N = 13) and sedentary (N = 11) Andean high-altitude natives performed an active orthostatic test. Eight of the trained subjects repeated the test 6-8 and 20-24 h after the end of a high-altitude marathon. Resting heart rate (HR) and the autonomic modulation of the heart were assessed by time domain and spectral analysis of HR variability (HRV): sympathetic (RR low frequency (LF)) and parasympathetic (RR high frequency (HF)) modulations, and sympathovagal balance (RR-LF:HF ratio). Results: Trained subjects exhibited a higher total power of HRV and a lower resting HR (+30%, P < 0.005) than sedentary subjects secondary to a higher and dominant parasympathetic modulation on sympathetic activity (RR-HF, RR-LF:HF ratio). At 6-8 h after the marathon, total power of HRV decreased (-69%), whereas resting HR increased from basal level (+22%), mainly because of a rise in sympathetic modulation (RR-LF, RR-LF:HF ratio). From 8 to 24 h of recovery, sympathetic modulation fell (RR-LF, RR-LF:HF ratio) and all HRV parameters were restored. Responses to the active standing position did not change between each recording session. Conclusion: Living in chronic hypoxia does not limit the training-induced benefits on the autonomic control of the cardiovascular system in Andean high-altitude ratives. The sympathetic predominance on the heart observed 6-8 h after the high-altitude marathon disappeared after 1 d of recovery. Therefore, living at high altitude does not impair the autonomic response to training

Mal de Montaña, migraña y depresión: ¿Coexistencia casual o causal? Posible rol de la hipoxia ambiental.

Objetivo: Estudiar la posible asociación entre mal de montaña crónico, migraña y depresión. Material y métodos: Estudio epidemiológico realizado en setiembre de 1990en 379 hombres adultos con residencia permanente en la ciudad de Cerro de Pasco (4300 m.s.n.m.); se hicieron 15 preguntas asociadas a depresión y 9 preguntas asociadas al mal de montaña crónico (MMC) con las que se calcularon puntajes de depresión y del mal de montaña crónico. Los puntajes por encima de dos desviaciones estándar de la media fueron considerados como altos. Resultados: La frecuencia de migrañas fue de 48.3% entre hombres con puntajes altos de MMC y de 26.5% entre aquellos con puntajes normales (p=0.013). El 16.7% de hombres con puntaje alto de MMC tuvo puntaje alto de depresión mientras que sólo el 6.5% con puntaje normal de MMC tuvo puntaje alto de depresión (p=0.04). El riesgo de tener puntaje alto de depresión o de MMC fue más del doble entre hombres con migrañas comparados con hombres sin migrañas. La posibilidad de tener migraña o puntajes alto de MMC, fue tres veces mayor entre hombres con puntajes alto de depresión comparados con los que tuvieron puntajes de MMC más altos que aquellos sin cefaleas o con otros tipos de cefaleas. Conclusiones: Los datos muestran una coexistencia más que casual entre estas tres entidades clínicas. Se sugiere que un factor de riesgo común a las tres sea la hipoxia crónica que podría producir cambios neuroquímicos en el cerebro que explicaría, en parte, los síntomas de estos tres síndromes. Los datos también sugieren que los síntomas subjetivos que ocurren en el mal de montaña crónico son similares a los que ocurren en la depresión

The catalytic role of a research university and international partnerships in building research capacity in Peru: A bibliometric analysis.

ObjectiveIn Peru, the past three decades have witnessed impressive growth in biomedical research catalyzed from a single research university and its investigators who secured international partnerships and funding. We conducted a bibliometric analysis of publications by Peruvian authors to understand the roots of this growth and the spread of research networks within the country.MethodsFor 1997-2016, publications from Web of Science with at least one author affiliated with a Peruvian institution were examined by year, author affiliations, funding agencies, co-authorship linkages, and research topics.ResultsFrom 1997-2016, the annual number of publications from Peru increased 9-fold from 75 to 672 totaling 6032. Of these, 56% of the articles had co-authors from the US, 13% from the UK, 12% from Brazil, and 10% from Spain. Universidad Peruana Cayetano Heredia (UPCH) was clearly the lead research institution noted on one-third of publications. Of the 20 most published authors, 15 were Peruvians, 14 trained at some point at UPCH, and 13 received advanced training abroad. Plotting co-authorships documented the growth of institutional collaborations, the robust links between investigators and some lineages of mentorship.ConclusionsThis analysis suggests that international training of Peruvian physician-scientists who built and sustained longstanding international partnerships with funding accelerated quality research on diseases of local importance. The role of a single research university, UPCH, was critical to advance a culture of biomedical research. Increased funding from the Peruvian Government and its Council for Science, Technology and Innovation will be needed to sustain this growth in the future. Middle-income countries might consider the Peruvian experience where long-term research and training partnerships yielded impressive advances to address key health priorities of the country

Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible Synergistic Mechanism for Altitude Pulmonary Hypertension?

Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed (p<0.01) and endothelial NOS mRNA increased (p<0.001), but the phosphorylated/nonphosphorylated vasodilator-stimulated phosphoprotein (VASP) ratio was unchanged. ADMA increased (p<0.001), whereas dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH (p<0.05). Although arginase activity increased (p<0.001) and L-arginine exhibited no changes, the L-arginine/ADMA ratio decreased significantly (p<0.001). Moreover, NOX4 expression increased only under CH (p<0.01), but malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (p<0.001). Our results suggest that ADMA and oxidative stress likely reduce NO bioavailability under altitude hypoxia, which implies greater pulmonary vascular reactivity and tone, despite the more subdued effects observed under CIH

Cardiovascular responses to orthostatic stress in healthy altitude dwellers, and altitude residents with chronic mountain sickness

High altitude (HA) dwellers have an exceptionally high tolerance to orthostatic stress, and this may partly be related to their high packed cell and blood volumes. However, it is not known whether their orthostatic tolerance would be changed after relief of the altitude-related hypoxia. Furthermore, orthostatic tolerance is known also to be influenced by the efficiency of the control of peripheral vascular resistance and by the effectiveness of cerebral autoregulation and these have not been reported in HA dwellers. In this study we examined plasma volume, orthostatic tolerance and peripheral vascular and cerebrovascular responses to orthostatic stress in HA dwellers, including some with chronic mountain sickness (CMS) in whom packed cell and blood volumes are particularly large. Eleven HA control subjects and 11 CMS patients underwent orthostatic stress testing, comprising head-up tilting with lower body suction, at their resident altitude (4338 m) and at sea level. Blood pressure (Portapres), heart rate (ECG), brachial and middle cerebral artery blood velocities (Doppler) were recorded during the test. Plasma volumes were found to be similar in both groups and at both locations. Packed cell and blood volumes were higher in CMS patients than controls. All subjects had very good orthostatic tolerances at both locations, compared to previously published data in lowland dwellers. In CMS patients responses of forearm vascular resistance to the orthostatic stress, at sea level, were smaller than controls (P < 0.05). Cerebral blood velocity was less in CMS than in controls (P < 0.01) and, at sea level, it decreased more than the controls in response to head-up tilting (P < 0.02). Cerebral autoregulation, assessed from the relationship between cerebral pressure and velocity, was also impaired in CMS patients compared to HA controls, when examined at sea level (P < 0.02). These results have shown that the good orthostatic tolerance seen in high altitude dwellers at altitude is also seen at sea level. There was no difference in orthostatic tolerance between CMS patients, with their exceptionally large blood volumes, and the HA controls. This may be because peripheral vascular and cerebrovascular responses (at least at sea level) are impaired in the CMS patients relative to HA controls. Thus, the advantage of the large blood volume may be offset by the smaller vascular responses