Revistas Científicas de la Universidad Peruana Cayetano Heredia
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    Estudio de pulmones de ratas con administracion de extracto de coca y drogas estimulantes de la respiracion

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    A study was done in hipersensibilidad of Sprague Dawley rats that were administered an extract of coca leaves with dimethyl sulfoxide (DMSO) as solvent, pure DMSO, almitrine and as control, oophorectomized rats. The lungs of the rats with extract of coca leaves and DMSO exhibit acute intralveolar hemorrhage as a predominant finding while those of rats with pure DMSO and almitrine had more intersticial mononuclear infiltrate that suggests, according to other studies, a hypersensitivity reaction. In the group of oophorectomized rats all of these findings were scarse and mild. A universal finding in the lungs of these rats were a thinckened arteriolar wall that seems to be a reactive to high altitude hypoxia as seen in other rodents in the same envinronment.Se hizo un estudio en pulmones de ratas Sprague Dawley bajo administración de un extracto de coca con dimetil sulfóxido (DMSO), DMSO puro, almitrina y, como controles, ratas ooforectomizadas. Los pulmones de las ratas con extracto de hojas de coca y DMSO muestran, como hallazgo predominante, hemorragia intra-alveolar aguda mientras que aquellos de ratas con solo DMSO y almitrina tienen más infiltrado mononuclear intersticial que sugiere, de acuerdo con otros estudios, una reacción de hipersensibilidad. En el grupo de ratas ooforectomizadas todos estos hallazgos fueron escasos y de grado leve. Un hallazgo universal en los pulmones de estas ratas fue el engrosamiento de la pared arteriolar que parece ser una reacción a la hipoxia de la altura como se observó en otros roedores en este mismo ambiente.

    Biological basis of chronic mountain sickness

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    The Andes completed its ´present elevation about 18 million years ago when mammals had already expanded at sea level about 65 millon years ago. Therefore mammals are recent invaders of the Andean high altitude. Andeans are newcomers to high altitude with only thousands of year of hypoxic exposition. High altitude is a great biological challenge for animal life and chronic mountain sickness is the result of this disease at sea level, where mamals evolved their respiratory function in the hyperoxic atmosphere. Chronic mountaain sickness constitutes an excessive response of physiological mechanisms which appear in the course of acclimatization of newcomers to high altitude or in high altitude natives, which eventually lead to symptoms of intolerance to the hypoxic environment. There is total loss of hyperventilation with PaO2 of 40 Torr in high altitude native with excessive polycythemia and symptoms of chronic mountain sickness compared with 32 Torr in the younger asymptomac ones (excessive hypoventilation). About 33% of the population living in Cerro de Pasco (4340 m) older than 50 years have concentrations of hemoglobin above 21.3 g/dl. In chronic mountain sickness is observed an exaggerated increase in arterial pulmonary hypertension, enlargement of the carotid bodies in high altitude natives and a high incidence of chemodectomas

    El Envejecimiento somático y la adrenopausia a nivel del mar y en la altura

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    The present study has been designed to deter- mine if adrenopause or reduction of serum adrenal an- drogens levels are observed early at high altitude than at sea level. It was determined also the relationship be- tween adrenopause with menopause in women living at sea level and at high altitude. Moreover, it was deter- mined the relationship of serum adrenal androgen levels with arterial oxygen saturation, hematocrit, and serum. levels of testosterone, and estradiol. The study has been performed in 210 women residents at high altitude (4340 m) aged 20-70 years and 123 women aged 20-70 years living in Lima (150 m). Results demonstrated that meno- pause was attained at earlier ages at high altitude than at sea level. Dehydroepiandrosterone (DHEA), its sulfate (DHEAS) and androstenedione (A) decline with age at sea level and at high altitude, however reduction is of major magnitude and attained earlier at high altitude than at sea level. The reduction of adrenal androgens pre- cedes elevation of FSH during perimenopause. In women at high altitude was also observed with aging a reduc- tion in arterial oxygen saturation with an increase of hematocrit and of the ratio testosterone/estradiol. The reduction of DHEA and A define adrenopause at sea level as well as at high altitude. Higher level of DHEA at high altitude was associated with low risk for excessive erythrocytosis. In conclusion, adrenopause is attained earlier and of major magnitude at high altitude than at sea level. The low level DHEA at high altitude was associated to a high risk for excessive erythrocytosis.El presente estudio fue diseñado para determinar si la adrenopausia o disminución de los andrógenos adrenales. se presenta a edad más temprana en la altura que a nivel del mar. Se determinó igualmente la relación de la adrenopausia con la menopausia en mujeres de nivel del mar y de la altura. Del mismo modo, se determinó la relación de los niveles de andrógenos adrenales con la saturación arterial de oxígeno, el hematocrito y los niveles de testosterona y estradiol. El estudio se ha realizado en 210 mujeres residentes en Cerro de Paseo, Perú (4340 m) de edades entre 20 y 70 años y en 123 mujeres de edades entre 20 y 70 años, que viven en Lima a 150 m sobre el nivel del mar. Los resultados demuestran que la menopausia se presenta a una edad más temprana en la altura que a nivel del mar. Con la edad se observa una disminución en los niveles de la dehidroepiandrosterona (DHEA) y su sulfato (DHEAS), y de la androstenediona (A), en la altura y a nivel del mar, siendo más temprana y la reducción de mayor magnitud en la altura que a nivel del mar; la disminución de los andrógenos adrenales precede a la elevación de la FSH sérica propia de la perimenopausia; igualmente se observa en las mujeres de la altura que con la edad hay una disminución de la saturación arte­ rial de oxígeno con aumento del hematocrito y de la relación testosterona/estradiol. Las disminuciones de los niveles de la DHEA y de la A son las que definen la adrenopausia tanto a nivel del mar como en la altura. Un mayor nivel de DHEA en la altura se asocia a un menor riesgo de eritrocitosis excesiva. En conclusión, la adrenopausia es más temprana y de mayor magnitud en la altura que a nivel del mar, con una fuerte asociación en la probabilidad de presentar eritrocitosis excesiva

    Evolution of hypoxia tolerance: Diving pinniped model and human hypobaric hypoxia model

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    To physiologists, the term 'adaptation' usually refers to any trait which is considered advantageous; evolutionary biologists restrict the definition to traits arising and maintained under selection. By their definition, many physiological traits may merely reflect inheritance passed on through lineage. In considering the evolution of tolerance to reduced oxygen availability, we studied the pininpeds where the two dominant groups, phocids and otariids, varying in diving capacities, and human lineages exposed for varying generational time periods to hypobaric hypoxia. Basic principles of evolution of complex physiological systems first emerged from analysis of the diving response. We then analyzed human responses to hypobaric hypoxia in three different lineages: lowlanders, Andean natives (Quechuas), and Himalayan natives (Sherpas). As in the pinniped example, we found 'conservative' and 'adaptable' physiological characters involved in human responses to hypoxia. Conservative characters are clearly dominant and are too numerous to outline in detail; three examples are hemoglobin oxygen affinities, muscle organization into different fiber types, and the brain's almost exclusive preference for glucose as a fuel. Most notably, we also found evidence for 'adaptable' characters at all levels of organization examined. At the whole body level in Quechuas and Sherpas, we found (i) that maximum aerobic and anaerobic exercise. capacities were down-regulated, (ii) that the acute effect of hypoxia (making up the energy deficit due to oxygen lack; i.e., the Pasteur effect) expected from lowlanders was blunted, and (iii) that acclimation effects were also attenuated. The biochemical behaviour of skeletal muscles was consistent with lowered reliance on anaerobic glycolytic contributions to energy supply, thus improved yield of ATP per mole of carbon fuel utilized. Heart adaptations also seemed to rely upon stoichiometric effficiency adjustments, improving the yield of ATP per mole of oxygen consumed (by using glucose in preference to fatty acids). Most of the biochemical and physiological adaptations we noted (both as acute and acclimation responses) were similar in Sherpas and Quechuas. These two lineages have not shared a common ancestor for about 1/3 of our species history, so we tentatively assume that their similar physiological traits arose independently as hypoxia defense adaptations in two different times and places in our history. As in the evolution of exquisitve capacities for management of oxygen down to vanishing low levels in diving animals, the evolution of human hypoxia tolerance can be described in terms of how two (consesative vs adaptable) categories of physiological characters are assembled in different human lineages and how the assembly changes through generational time. More recent evidence indicating that our species evolved under 'colder, drier, and higher' conditions, suggests that these adaptations may represent the 'ancestral' physiological condition for humans.

    Adaptation to high altitude: Effects of small changes in the regulatory behavior of the andean chicken hemoglobin

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    A strain of high altitude chickens (Gallus gallus) displaying a high oxygen affinity hemoglobin has been discovered in the Peruvian Andes. We addressed the question of the molecular mechanism possibly at the origin of the high altitude adaptation of these chickens. The role of small changes of the intracellular concentration of inositol pentaphosphate (IPP), the main allosteric effector of hemoglobin in avian erythrocytes, has been postulated. We have studied the blood from andean and sea-level born chickens. The oxygen affinities of fresh red blood cells (RBC) suspensions are significantly increased in andean compared to sea-level chicken blood. The values of the Hill coefficients at half-saturation (n50) are higher for chicken RBC than those observed for mammalian RBC. This may suggest the existence of a molecular aggregation process inside the deoxygenated, highly concentrated cells of both avian types. For the stripped purified hemolysate solutions of the two types of chickens, the oxygen affinities are identical in phosphate-free buffer. indicating that the intrinsic oxygen affinities of andean and sea-level Hbs are the same. Upon addition of inositol hexaphosphate (IHP), a strong allosteric effector of avian hemoglobins, we observed a small but significant increase (about 20%) of the oxygen affinity of the andean relatively to sea-level hemolysates. Our results also suggest that the difference in affinity between the sea-level and andean blood may be due to an adaptative process possibly related to a slight decrease in the concentration and/or of the activity of the main cellular effector IPP, rather than to a structural abnormality of the hemoglobin.

    Triple Hypoxia Syndrome

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    Many patients with excessive erythrocytosis (EE), with hematocrit greater than 55%, but lower than 70%, apparently are normal. They work. play soccer, develop intellectual activities and frequently perform better than sedentary normal people (3500 m). They request medical attention, only when they present symptoms similar to those of acute mountain sickness (AMS), such as: headache, dyspnea, nausea, lassitude and indigestion. Without going higher they have been said to experience "sorojchi (AMS) in bed". They show extreme hypoxia with an oxygen arterial tension (PaO2) near 20 mmHg, with or withouthypercapnia and a normal or acidotic pH. We have previously named this complication of EE, as the triple hypoxia syndrome (THS). It is due to: [1] Normal high altitude adaptation to hypoxia, [2] EE hypoxia (CMS) and [3] acute hypoxia that can be reversed by oxygen. The THS is similar to "surviving" on the summit of Mount Everest. It may be caused by viral infections ( flu ) or some other acute respiratory disease, with malaise that lasts several days without treatment and trypically is reversed by 24 hours of oxygen to PaO2 baseline values of their chronic condition with EE. The diagnosis is important, since the THS is an acute transitory condition, that when not recognized and treated with oxygen can possibly lead to cardiac, pulmonary or cerebral complications

    Physiological changes related to rapid altitude shifts in La Paz, Bolivia

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    Due to the bowl shaped topography of La Paz, Bolivia, the residents of the city are constantly changing altitude from 3100 meters, in a common residential area to 4100 m at El Alto, an upper industrial city and airport area. In order to access cardio­respiratory alterations occurring with rapid altitude changes, 15 soldiers [average age = 19 years, Weight = 59.07 Kg., Heigh = 165 cm], residents of El Alto (4000 m), were examined in a mobil unit equipped with a computerized cardio-ventilatory apparatus. Following calibration of the ventilatory apparatus, and after 15 minutes of rest, over the next 6 hours, subjects were connected via mouthpiece to a one way flow valve for 15 minutes. Expired gas was collected in Douglas bags. The electrocardiogram was monitored with 3 standard chest leads. Finger oximetry was recorded. Blood was drawn for arterial gases analysis. These were analyzed at 3600m with a Radiometer Blood Gas MK2 pH. The same procedure was repeated the next day on descent to the forest of Aranjuez (3100 m). Saturation rose from 87.8 ± 2.83% to 91.47 ± 1.40% (p< .001). Heart rate changed from 72.5 ± 10.2 to 68.3 ± 7.9 (p< .05) beats per minute. Alveolar ventilation (BTPS) diminished from 7,117 ± 1,232 ml to 6,197 ±  844 ml (p < .05). Oxygen consumption greatly increased from 172 ±  30 to 300 ± 42 ml/min (p < .001). Carbon dioxide production did not change significantly 266 ± 43.23 to 245 ± 32 ml/min. The respiratory Quotient diminished from 1.5 to 0.8 Arterial partial oxygen tension (PaO2) increased from 54 ± 2.79 to 64 ± 6.33 mmHg (p< .001). PaCO2 changed from 33 ± 2.2 to 34 ± 1.57 (p < .05). The pH decreased from 7.434 ± 0.026 to 7.381 ± 0.335 (p< .001). This research demonstrates that when patients are analyzed in a cardio­-pulmonary laboratory after they descend or ascend to it, the change in altitude must be considered in interpretation of results. Rapid altitude shifts in La Paz, force residents to constantly adapt, producing respiaratory acidosis on descent within the city

    Can HAPE be diagnosed through the tongue?

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    High Altitude Pulmonary Edema (HAPE) is an acute illness with dramatic mamfestations in the lung that also affects all systems of the body. Hence, very careful observations are required to discover all of these manifestations. It is our observation that patients with HAPE frequently have ulcers on the tongue. The tongue appears white with one or more reddish colored ulcers that have rough irregular borders. It is non painful and without bleeding. The alterations of the mucosa of the tongue appear similar to geographic tongue. lt seems to be related to the severity of the HAPE, and disappears rapidly with oxygen treatment of the pulmonary edema. Over the past two years, we have seen 6 cases of HAPE of whom 4 presented with tongue ulcers. The other two cases 'tongues were pale white and could have formed ulcers had they not received oxygen therapy. The origin of the ulcers is unknown, although it has been hypothesized to be manifestation of viral infection, associated to peripheral vasoconstriction, and/or dehydration

    Efecto de la menopausia en la relación entre las presiones alveolares de O2 y C2 y el Mal de Montaña Crónico

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    En este estudio pretende determinar el rol que tiene la llegada de la menopausia en la relación entre las presiones alveolares de O2 y C2 y el Mal de Montaña Crónico (MMC) o Enfermedad de Monge. El estudio se realizó en una muestra poblacional femenina residente de Cerro de Pasco (4,300 m) entre los 26-62 años de edad (n=41). Se midieron, entre otras, las variables fisiológicas involucradas en la secuencias fisiopatológica del MMC: presiones tidales de O2 y C2 (P02 T y PC02T, torr), saturación de oxígeno (SaO2%), y concentración de hemoglobina (Hb, g/dl). Los resultados mostraron que, en las mujeres de altura después de la menopausia, se observa una disminución de la P02T (48.4 ± 3.3 vs 52.7 ± 3.1 torr; p<0.0001) y de la SaO2 (81.9 ± 4.12 vs 84.7 ±3.14%; p<0.0001), así como un aumento de la PC02T (34.5 ± 2.2 vs. 30.4 ± 3.3. torr; p<0.0001) y de la Hb (18.6 ± 1.7 vs 15.9 ± 2.3 g/dl; p<0.001). En las poblaciones masculinas de altura se observa un aumento de la prevalencia de eritrocitosis excesiva en forma continua con la edad, en el caso de las mujeres de altura, postulamos, en base a nuestros resultados, que un factor contribuyente adicional para la aparición abrupta (y no continua) del MMC sería la disminución de la ventilación, como lo indica el aumento de la PC02T. Esta, al disminuir, traería como consecuencia hipoxemia y eritrocitosis excesica, el signo preponderante del MMC.

    Mal de montaña agudo. Mecanismos Fisiopatológicos

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    Se desarrollan las bases fisiológicas de la aclimatación a la hipoxia en función de las modificaciones que se observan en los sistemas respiratorio, y cardiovascular, así como en el transporte de oxígeno en la sangre. Se presentan las etapas de aclimatación a la altura en relación a la sintomatología y a los cambios fisiológicos que ocurren a lo largo de la aclimatación a la hipoxia aguda. Se describen las enfermedades provocadas por la exposición aguda a la altura (Mal de Montaña Agudo -MMA- Edema pulmonar de altura - EPA-, Edema Cerebral de altura - ECA-), así como los mecanismos involucrados y las consecuencias de la aparición de las mismas. Se postula que la superposición de hallazgos en las enfermedades mencionadas impide definir los limites clínicos exactos de estas condiciones patológicas con claridad

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