Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

Hebbel, Robert P.; Eaton, John W.; Kronenberg, Richard S.; Zanjani, ED; Moore, Lorna G.; Berger, E.

doi:10.1172/jci109165

Cited by 117 publications

(62 citation statements)

References 29 publications

(40 reference statements)

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“…Furthermore, we verified the general contention that the higher oxygen affinity of blood is advantageous for oxygen transport under severe hypoxia (LAHIRI, 1975;HEBBEL et al, 1978), using plasma Epo level as a keen index for tissue hypoxia. As the importance of inhibitory factor(s) in the regulation of erythropoiesis has become recently appreciated (NAIMAN et al, 1987), the temporal pattern in hypoxic mice was also examined.…”

supporting

confidence: 65%

Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Shimizu¹,

Satoh²,

Enoki³

et al. 1989

Jpn.J.Physiol

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Temporal changes of plasma erythropoietin (Epo) in mice exposed to hypobaric hypoxia were studied by a fetal mouse liver cell culture method. Since a colony formation inhibitory activity was found in the mouse plasma, thirteen pretreatment procedures for bioassay were compared and the procedure of shaking with chloroform followed by dialysis was concluded to be the best. When normal mice (P50 = 40.4 + 2.2 Torr) were exposed to hypoxia of 350 Torr, the plasma Epo level was elevated, with peak at the 2nd to 3rd day, and afterwards declined gradually. On the contrary, cyanated mice (P50 = 30.1 + 1.5 Torr) showed much less of the Epo response when exposed to 350 Torr. Under 200 Torr hypoxia, both mice exhibited a similar and remarkable extent of the response. These results suggest that the renal Epo-producing tissue or its oxygen-sensing system is less hypoxic in cyanated mice than in normal mice under 350 Torr, and that the physiologically optimal oxygen affinity of blood is variable depending on hypoxic degrees. The fact that the inhibitory activity showed an inverse temporal change to that of Epo, suggested a possible important role of this activity in the regulation of erythropoiesis under hypoxia.

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supporting

confidence: 65%

Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Shimizu¹,

Satoh²,

Enoki³

et al. 1989

Jpn.J.Physiol

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“…Even at low altitude, a left-shifted curve might be advantageous when the rate of O 2 transfer across the blood-gas interface is diffusion limited, as is the case during intense exercise (Bencowitz et al, 1982). In rats, a pharmacologically increased Hb-O 2 affinity was shown to greatly enhance metabolic performance and survival under conditions of extreme hypoxia (Eaton et al, 1974;Turek et al, 1978a;Turek et al, 1978b), and human subjects with mutant Hbs that exhibit increased O 2 affinity (Hb Andrews-Minneapolis) maintain normal arterial O 2 saturation and undiminished aerobic capacity at high altitude (3100m) relative to subjects with wild-type Hb (Hebbel et al, 1978). It therefore appears that the DPG response of lowlanders might be maladaptive at high altitudes.…”

Section: Blood-o 2 Affinitymentioning

confidence: 99%

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Storz

Scott

Cheviron

2010

Journal of Experimental Biology

346

343

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SummaryHigh-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high-and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

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“…The benefit of increased Hb affinity for O 2 was assessed during an investigation of two children with mutant Andrew-Minneapolis Hb, which has a higher than normal affinity for O 2 , and their two siblings with normal Hb (Hebbel et al, 1978). When taken to high altitude the children with mutant Hb had better exercise tolerance, as indicated by lower increments in resting heart rate.…”

Section: Benefits Of a Leftward Shiftmentioning

confidence: 99%

“…They then found that cyanate-treated rats maintained better oxygen transfer to tissues during severe hypoxia than did normal animals. Hebbel et al (1978) studied a family in which two out of the four children have mutant AndrewMinneapolis Hb, with a P 50 of 17.1 mmHg. The increased O 2 affinity of the mutant Hb seemed to confer a sort of pre-adaptation to altitude; at a moderate altitude of 3100 m, the mutant Hb siblings exhibited lower increases in resting heart rates than their normal siblings and minimal increases in plasma and urinary EPO levels, while they did not exhibit thrombocytopenia or decrements in O 2 consumption.…”

mentioning

confidence: 99%

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

Balaban

Duffin

Preiss

et al. 2013

Respiratory Physiology & Neurobiology

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Some animals have adapted to hypoxia by increasing their haemoglobin affinity for oxygen, but in vitro studies have not shown any change of haemoglobin affinity for oxygen in human high altitude natives or lowlanders acutely acclimatized to high altitude. We conducted the first in vivo study of the oxyhaemoglobin dissociation curve by progressively reducing arterial PO 2 while maintaining normocapnia in lowlanders at sea level, lowlanders sojourning at 3600m for two weeks and native Andeans at the same altitude. We found that the in vivo PO 2 at which haemoglobin is half-saturated (P 50 ) is higher in lowlanders at sea level (32 mmHg) than that measured in vitro (27 mmHg) and that lowlanders and highlanders do significantly increase the in vivo affinity of their haemoglobin for oxygen with exposure to high altitude. These results indicate the value of an in vivo approach for studying the oxyhaemoglobin dissociation curve.iii

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Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

Cited by 117 publications

References 29 publications

Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Temporal changes of plasma erythropoietin level in hypobaric hypoxic mice and the influence of an altered blood oxygen affinity.

Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

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