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Biomedical subjects

C Monge

Publications and source records attributed to C Monge.

At least 19 recordsLinked to original sources
PubMed2000

Evolution of human hypoxia tolerance physiology.

Analysis of human responses to hypobaric hypoxia in different lineages (lowlanders, Andean natives, Himalayan natives, and East Africans) indicates 'conservative' and 'adaptable' physiological characters involved in human responses to hypoxia. Conservative characters, arising by common descent, dominant and indeed define human physiology, but in five hypoxia response systems analyzed, we also found evidence for 'adaptable' characters at all levels of organization in all three high altitude lineages. Since Andeans and Himalayans have not shared common ancestry with East Africans for most of our species history, we suggest that their similar hypoxia physiology may represent the 'ancestral' condition for humans--an interpretation consistent with recent evidence indicating that our species evolved under 'colder, drier, and higher' conditions in East Africa where the phenotype would be simultaneously advantageous for endurance performance and for high altitude hypoxia. It is presumed that the phenotype was retained in low capacity form in highlanders and in higher capacity form in most lowland lineages (where it would be recognized by most physiologists as an endurance performance phenotype). Interestingly, it is easier for modern molecular evolution theory to account for the origin of 'adaptable' characters through positive selection than for conserved traits. Many conserved physiological systems are composed of so many gene products that it seems difficult to account for their unchanging state (for unchanging structure and function of hundreds of proteins linked in sequence to form the physiological system) by simple models of stabilizing selection.

Acclimatization↗
PubMed2000

Hemoglobin affinity for oxygen in three subspecies of toads (Bufo sp.) living at different altitudes.

Blood oxygen affinity and red blood cell properties were measured in three subspecies of genus Bufo: Bufo spinulosus limensis, collected at sea level and at an average day temperature of 20 degrees C; Bufo spinulosus trifolium, from 3100 m, average day temperature of 15 degrees C; and Bufo spinulosus flavolineatus, from 4100 m, average day temperature of 10 degrees C. Electrophoresis of the hemoglobin showed the same component in each of the three subspecies. At 20 degrees C the blood oxygen affinities (P50) showed small differences between Bufo spinulosus limensis and Bufo spinulosus trifolium, whereas the value for Bufo spinulosus flavolineatus was markedly lower. At 10 degrees C, the ambient temperature of Bufo spinulosus flavolineatus, the P50 was extremely low compared with the other two subspecies at their corresponding ambient temperatures.

Adaptation, Physiological↗
PubMed1999

Adaptation and conservation of physiological systems in the evolution of human hypoxia tolerance.

Analysis of human responses to hypobaric hypoxia in different lineages (lowlanders, Andean natives, Himalayan natives, and East Africans) indicates 'conservative' and 'adaptable' physiological characters involved in human responses to hypoxia. Conservative characters, derived by common descent, dominate and indeed define human physiology, but in five hypoxia response systems analyzed, we also found evidence for 'adaptable' characters at all levels of organization in all three high altitude lineages. Since Andeans and Himalayans have not shared common ancestry with East Africans for most of our species history, we suggest that their similar hypoxia physiology may represent the 'ancestral' condition for humans--an interpretation consistent with recent evidence indicating that our species evolved under 'colder, drier, and higher' conditions in East Africa where the phenotype would be simultaneously advantageous for endurance performance and for high altitude hypoxia. It is presumed that the phenotype was retained in low capacity form in highlanders and in higher capacity form in most lowland lineages (where it would be recognized by most physiologists as an endurance performance phenotype). Interestingly, it is easier for modern molecular evolution theory to account for the origin of 'adaptable' characters through positive selection than for conserved traits. Many conserved physiological systems are composed of so many gene products that it seems difficult to account for their unchanging state (for unchanging structure and function of hundreds of proteins linked in sequence to form the physiological system) by simple models of stabilizing selection.

Adaptation, Physiological↗
PubMed1997

Changes in whole blood oxygen affinity and eggshell permeability in high altitude chickens translocated to sea level.

High altitude (HA; n = 5) chickens (Gallus gallus) with a high oxygen hemoglobin (Hb) affinity were transported from their birthplace (Puno, Perú 4,000 m) down sea level (Lima, Perú). The in vivo whole blood oxygen affinity (P50) and the eggshell permeability (P) were studied after several months living at sea level and in the first (F1) and second (F2) generations born at sea level. Our approach was to analyze changes in Hb affinity and eggshell permeability, considered as indicators of HA adaptation in birds. Our results show an increase of the P50 values (a decrease in Hb affinity) towards sea-level values. The results in P indicate that this variable increases towards sea level values in the F2 generation. We conclude that in the Andean chicken, a relative "newcomer" to high altitude (no more than 500 years), neither the Hb affinity for oxygen nor the eggshell permeability are invariable indicators of HA adaptation, in contrast with other native high altitude mammals and birds.

Acclimatization↗
PubMed1997

The role of menopause in the development of chronic mountain sickness.

The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE, measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMSscore) were measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%, P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.

Adult↗
PubMed1996

Hemoglobin affinity and structure in high-altitude and sea-level carnivores from Peru.

We compared hemoglobin affinity (P50) and structure of high altitude (HA) carnivores with populations of the same species or genus living at sea level (SL). P50 was measured in cats, pumas and foxes. It differed in animals occupying both niches. SL: cat 29.3 torr, puma 36.3 torr, fox 26.2 torr; HA: cat 22.5 torr, puma 31.1 torr, fox 18.5 torr. Heme and globins were fractionated by HPLC. Puma and fox hemoglobins also showed structural differences. P50 is lower in genotypically HA-adapted species studied and can differentiate SL and HA populations of the same species.

Altitude↗
PubMed1996

Fetal and maternal blood oxygen affinity: a comparative study in llamas and sheep.

We compared blood oxygen affinity (P50) and hemoglobin concentration among fetal and maternal llamas and sheep, as respective examples of species native to high and low altitudes. P50, hemoglobin concentration and blood oxygen content were determined at sea level in 16 pregnant llamas, 6 pregnant sheep and their respective fetuses. P50 was similar in fetal llamas and sheep, but maternal llamas had higher blood oxygen affinity than maternal sheep. As a consequence, the P50 difference between mother and fetus was less in llamas than in sheep. Fetal llamas had higher hemoglobin concentrations than fetal sheep. In contrast, the maternal hemoglobin concentrations were similar. The blood oxygen content was higher in fetal and maternal llamas than in fetal and maternal sheep. We conclude that the llama, a species native to the altiplano, has a higher blood oxygen content than the sheep, as determined in the fetus by a high hemoglobin concentration and in the mother by a low P50.

Animals↗
PubMed1996

Sherpa brain glucose metabolism and defense adaptations against chronic hypoxia.

The brain of hypoxia-tolerant vertebrates is known to survive extreme oxygen limitation at least in part because of very low rats of ATP utilization and ATP production. To asses whether similar adaptations are involved in healthy humans during hypoxia adaptation over generational time, we initially used positron-emission tomography measurements of glucose metabolic rates in the brain of Quechuas, whose ancestors have been indigenous to the Andes at altitudes between approximately 3,300 and 4,500 m for several hundred years. Workers in this field generally believe that the lineage of Sherpas has been indigenous to the Himalayas for even longer and that Sherpas and other peoples indigenous to the Tibetan plateau are perhaps the most exquisitely hypoxia adapted of all humans. For this reason, in this study we extended our database to include Sherpas. With the use of the same protocol as before, two metabolic states were analyzed: 1) the presumed normal (hypoxia-adapted) state, monitored as soon as possible after subjects left the Himalayas and 2) the deacclimated state, monitored after 3 wk at low altitudes. Positron-emission tomography measurements of 2-[18F]deoxy-2-fluoro-D-glucose metabolic rates, quantified in 26 regions of the brain, indicated that the Sherpas' brain metabolism differed significantly from that of Quechuas but was essentially identical to that of lowlanders. Region-by-region patterns were similar in all three groups, indicating that the regional organization of glucose metabolism in the brain is a conservative, relatively constant characteristic.

Adaptation, Physiological↗
PubMed1994

Similarity of PO2 and PCO2 values in the air cell of eggs of birds and in the alveolar gas of humans at sea level and at high altitude.

At the end of incubation, the partial pressures of oxygen and carbon dioxide in the air cell of sea-level avian eggs are similar to those in the expiratory air of adult birds. At high altitude, changes in the permeability of the shell and probably in the embryo metabolism partially compensates the increase in the gas diffusion constant resulting from the low barometric pressure. The aim of this study was to test whether--despite of the adaptive responses of the high altitude avian embryo--the air cell values would be similar to those of the alveolar air of high altitude human natives. Air cell O2 (48.3 +/- 1.6 torr) and CO2 (20.9 +/- 0.85 torr) pressure values were obtained by studying naturally incubated eggs of the Andean gull (Larus serranus) at 4650 m. Sea-level chicken (Gallus gallus) air cell pressure values of O2 (102.3 +/- 2.7 torr) and of CO2 (43.3 +/- 1.3 torr) were obtained from the literature for comparison. Both these values were similar to those found in the alveolar air of humans at sea level (O2: 104.4 +/- 0.4 torr, CO2: 40.1 +/- 0.25 torr) and at high altitude (4540 m) (O2: 50.5 +/- 0.53 torr, CO2: 29.1 +/- 0.37 torr). Despite very large evolutionary changes in morphology and physiology of the respiratory organs, the head pressure of O2 that oxygenates the blood keeps a constant value in the pre-pipping avian embryo and in the alveolar air of adult mammals. This constancy holds valid at high altitude.

Altitude↗
PubMed1994

Inhibitory effect of an alpha 1-adrenergic antagonist on erythropoiesis in normoxic or hypoxic mice.

The present study was undertaken to assess the effect of prazosin, a selective postsynaptic alpha 1-adrenergic receptor blocking agent, on normoxic and hypoxic mice, in order to evaluate experimentally its use in the treatment of the excessive erythrocytosis that characterizes chronic mountain sickness. The drug, injected intraperitoneally to adult mice at a dose of 400 micrograms/kg per day, induced a significant depression of the rate or erythropoiesis, as measured by red blood cell 59iron uptake, with a decrease in the hematocrit from the 3rd day. The drug also inhibited the oxygen-dependent secretion of erythropoietin (estimated by the plasma immunoreactive hormone concentration) in hypoxemic mice when injected between 0 and 2 h after initiation of the hypoxic stimulation. When injected daily into mice exposed to intermittent hypobaric hypoxia, prazosin limited the degree of polycythemia or induced a sustained decrease in the hematocrit when polycythemia was already present due to previous exposure. It is postulated that the drug, by reducing the peripheral vascular resistance seen during hypoxia, could increase renal blood flow, thus improving the renal oxygen supply and partially restoring the imbalance between gas supply and demand, which drives erythropoietin formation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Bone marrow oxygen consumption and erythropoiesis in chronically hypoxic rats.

Bone marrow oxygen consumption (VO2) was determined weekly in 16 Holtzman rats exposed to continuous hypobaric hypoxia (CHH) during 30 days. The results were compared with those obtained in 10 sea level control animals (SL). The VO2 expressed as ng.at.O2/min, decreased progressively with time of exposure to hypoxia. VO2 (mean +/- SD) was 0.0936 +/- 0.135 in SL rats. In CHH animals, it was 0.1001 +/- 0.0292 after 8 days of hypoxia, 0.1030 +/- 0.0206 after 16 days, 0.0594 +/- 0.0148 (p = 0.002) after 24 days and 0.0136 +/- 0.404 (p = 0.000) after 30 days. Protein concentration in bone marrow was progressively higher in hypoxics when compared to control, with significant differences since the first week of exposure. Blood hemoglobin increased in parallel to protein concentration in the bone marrow. These findings suggest an increase in the cells of the erythroid series whose oxygen consumption is less than cells in the early stages of differentiation. The increased protein concentration is in agreement with the fact that globin mRNA appears in cells with a progressively increasing anaerobic metabolism at relatively late stages of erythropoiesis.

Animals↗
PubMed1994

Ventilatory response to severe acute hypoxia in guinea-pigs and rats with high hemoglobin-oxygen affinity induced by cyanate.

Baseline ventilation, hemoglobin concentration (Hb) and P50 were significantly lower in guinea-pigs than in rats. Chronic sodium cyanate (NaOCN) administration did not significantly increase hemoglobin concentration in either guinea-pigs or rats. It decreased the P50 significantly less in guinea-pigs than in rats. The high Hb-O2 affinity experimentally induced did not modify the hypoxic ventilatory response (HVR) of guinea-pigs and rats. At the same level of acute hypoxia, HVR was significantly lower in NaOCN guinea-pigs than in NaOCN rats. Guinea-pigs, genotypically adapted animals to high altitude, displayed relatively minor ventilatory and Hb-O2 affinity changes to NaOCN, and a relatively minor HVR to acute hypoxia. They probably use tissue and biochemical adaptive mechanisms, in addition to their limited extracellular responses to successfully tolerate ambient hypoxia.

Acute Disease↗
PubMed1993

High altitude tissue adaptation in Andean coots: capillarity, fibre area, fibre type and enzymatic activities of skeletal muscle.

Capillarity, fibre types, fibre area and enzyme activities of different skeletal muscles (pectoralis, extensor digitorum longus), tibialis anterior, plantaris and the myocardium) were compared in Andean coot (Fulica americana peruviana) native to high altitude (Junín, Perú, 4200 m) and the same species nesting at sea level. Numbers of capillaries per square millimeter were higher in all high-altitude muscles when compared with sea-level muscles (P < 0.0001). Moreover, values for capillaries per fibre and capillaries in contact with each fibre were higher in digitorum and tibialis high-altitude muscles. Muscle fibres were classified as Type I, Type IIA or Type IIB on the basis of their myofibrillar ATPase pH lability. Pectoralis muscle of high-altitude and sea-level coots presented only fibres of Type IIA. In contrast, all the leg muscles studied showed a mosaic pattern of the three fibre types. Fibre areas were determined using a Leitz Texture Analysis System. Significant differences in fibre area were observed (P < 0.01) between high-altitude and sea-level muscles. Mean muscle fibre diameters were also lower in the high-altitude group than in the sea-level group. The enzyme activities studied were hexokinase, lactate dehydrogenase, citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase. The oxidative capacity, as reflected by citrate synthetase and hydroxyacyl-CoA-dehydrogenase activities, was greater for myocardial and pectoralis than for leg muscles. However, analysis of maximal enzyme activities showed that there were no significant differences between the glycolytic and oxidative enzyme activities of high-altitude and sea-level coots.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1993

Blood gases, pH and hematology of montane and lowland coot embryos.

Blood gases, air cell-blood gas differences, blood pH, and hematology were compared in embryonic coots (Fulica americana peruviana) at 4150 m and sea level in Peru. Neither arterialized nor venous O2 tensions differed significantly between montane and lowland groups but blood CO2 tensions of the two groups differed significantly. The air cell PO2-arterialized blood PO2 difference of montane eggs was less than half the value in lowland eggs. Both arterialized and venous CO2 tensions differed substantially between montane and lowland groups. Despite these differences, plasma pH at both altitudes was statistically indistinguishable, due in part to variation in plasma [HCO3-]. Hematocrits of montane embryos were significantly higher than that of their lowland counterparts.

Altitude↗
PubMed1992

Effects of cocaine on oxygen consumption and mitochondrial respiration in normoxic and hypoxic mice.

The administration of cocaine hydrochloride intraperitoneally (25 mg/kg) produces a drop in VO2 in both normoxic and hypoxic mice. The critical PO2 is also decreased and so is the body temperature. The mitochondrial respiration shows a large fall in ST3 and RCR. The addition of cocaine in-vitro to the incubating medium induces changes in the mitochondrial respiration similar to those found after in-vivo administration. This report shows that in addition to its in-vivo actions cocaine alters the respiratory function of the isolated liver mitochondria.

Animals↗
PubMed1992

Enzyme mechanisms for pyruvate-to-lactate flux attenuation: a study of Sherpas, Quechuas, and hummingbirds.

During incremental exercise to fatigue under hypobaric hypoxia, Andean Quechua natives form and accumulate less plasma lactate than do lowlanders under similar conditions. This phenomenon of low lactate accumulation despite hypobaric hypoxia, first discovered some half century ago, is known in Quechuas to be largely unaffected by acute exposure to hypoxia or by acclimatization to sea level conditions. Earlier Nuclear Magnetic Resonance (NMR) spectroscopy and metabolic biochemistry studies suggest that closer coupling of energy demand and energy supply in Quechuas allows given changes in work rate with relatively modest changes in muscle adenylate and phosphagen concentrations, thus tempering the activation of glycolytic flux to pyruvate--a coarse control mechanism operating at the level of overall pathway flux. Later studies of enzyme activities in skeletal muscles of Quechuas and of Sherpas have identified a finely-tuned control mechanism which by adaptive modifications of a few key enzymes apparently serves to specifically attenuate pyruvate flux to lactate.

Adaptation, Physiological↗
PubMed1991

Metabolic effects of cyanate on mice at sea level and in chronic hypobaric hypoxia.

In order to evaluate the toxic effects of Sodium Cyanate (NaOCN), it was orally administered to growing mice at sea level (SL-CN) and to mice chronically exposed to intermittent hypobaric hypoxia (IHH-CN). The effects on body weight, in-vivo O2 consumption (VO2) and the respiratory function of liver mitochondria were evaluated. At sea level, the animals on cyanate lost weight in contrast with the controls that gained weight. When exposed to IHH, the controls lost weight and the animals on cyanate regained weight. After 2 months observation the weights of the IHH-CN and IHH-C were similar. The VO2 after one month of treatment was similar in the SL-C and in the SL-CN but it was lower in the IHH-CN when compared with IHH-C. The substrate-stimulated respiration of isolated liver mitochondria (ST4) was not affected by NaOCN, but the ADP-stimulated respiration (ST3) was reduced. The ratio ST3/ST4 (RCR) was also lower. These changes were present in both SL and in IHH and were much larger after three months of treatment. The toxic effects of chronic administration of NaOCN are discussed.

Administration, Oral↗