Exsanguination Cooling

Ikeda, Sadao

doi:10.1620/tjem.87.185

Cited by 3 publications

(4 citation statements)

References 3 publications

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“…Our proposed mechanism for the erythrocyte's role is supported by observations that hypoxia can induce torpor in pocket mice [19]. In addition, exsanguination is known to be associated with a reduction in T b [20]. Together, these observations support the role of erythrocytes in mediating hypoxia regulation of T b .…”

Section: Discussionsupporting

confidence: 72%

AMP Deaminase 3 Deficiency Enhanced 5′-AMP Induction of Hypometabolism

et al. 2013

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A hypometabolic state can be induced in mice by 5′-AMP administration. Previously we proposed that an underlying mechanism for this hypometabolism is linked to reduced erythrocyte oxygen transport function due to 5′-AMP uptake altering the cellular adenylate equilibrium. To test this hypothesis, we generated mice deficient in adenosine monophosphate deaminase 3 (AMPD3), the key catabolic enzyme for 5′-AMP in erythrocytes. Mice deficient in AMPD3 maintained AMPD activities in all tissues except erythrocytes. Developmentally and morphologically, the Ampd3−/− mice were indistinguishable from their wild type siblings. The levels of ATP, ADP but not 5′-AMP in erythrocytes of Ampd3−/− mice were significantly elevated. Fasting blood glucose levels of the Ampd3−/− mice were comparable to wild type siblings. In comparison to wild type mice, the Ampd3−/− mice displayed a deeper hypometabolism with a significantly delayed average arousal time in response to 5′-AMP administration. Together, these findings demonstrate a central role of AMPD3 in the regulation of 5′-AMP mediated hypometabolism and further implicate erythrocytes in this behavioral response.

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Section: Discussionsupporting

confidence: 72%

AMP Deaminase 3 Deficiency Enhanced 5′-AMP Induction of Hypometabolism

et al. 2013

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“…However, inhibition of hexokinase, the first enzymatic step of glycolysis, by 2-deoxygluocose would severely impact the ability of erythrocytes to produce ATP. In addition, hypothermia of mammals can be induced by exsanguination, a process in which a large volume of blood is removed from the body (3,26). Furthermore, hypothermia is a documented response to prolonged hypoxia (4).…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon also illustrates the important role of oxygen transportation by erythrocytes in metabolic activity. In addition, observations that exsanguination and prolonged hypoxia can result in hypothermia further demonstrate the importance of oxygen transportation and availability as factors that can modulate the metabolic rate in mammals (3,4).…”

Section: Mammals In Deep Hypometabolism (Dh)mentioning

confidence: 96%

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

Daniels

Zhang

O’Brien

et al. 2010

Journal of Biological Chemistry

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Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5-AMP uptake by erythrocytes. Wild type, ecto-5-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5-AMP-induced hypometabolism in a similar fashion. Injection of 5-AMP leads to two distinct declining phases of oxygen consumption (VO 2 ). The phase I response displays a rapid and steep decline in VO 2 that is independent of body temperature (T b ) and ambient temperature (T a ). It is followed by a phase II decline that is linked to T b and moderated by T a . Altering the dosages of 5-AMP from 0.25-to 2-fold does not change the phase I response. For mice, a T a of 15°C is effective for induction of DH with the appropriate dose of 5-AMP. Erythrocyte uptake of 5-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5-AMP administration and is in parallel with the phase I decline in VO 2 . In summary, our investigations reveal that 5-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5-AMP. Mammals in deep hypometabolism (DH)5 with severe hypothermia and stupor are only observed naturally during hibernation (1). During hibernation, an animal's overall metabolic rate, based on oxygen consumption, is a small fraction of its euthermic needs. The biochemical event that triggers this hypometabolism is an enigma. It is thought that non-hibernating mammals cannot undertake a similar hypometabolic process because deep hypothermia is often associated with ventricular fibrillation and cardiac arrest.However, organs from non-hibernators can withstand a considerable ischemic period in a hypometabolic state. For example, during human organ transplantation, donated organs are transported in a cold ischemic state in the complete absence of blood circulation for many h (2), yet when implanted into a recipient, the restoration of blood flow and rewarming revives full organ function. This phenomenon also illustrates the important role of oxygen transportation by erythrocytes in metabolic activity. In addition, observations that exsanguination and prolonged hypoxia can result in hypothermia further demonstrate the importance of oxygen transportation and availability as factors that can modulate the metabolic rate in mammals (3, 4).We have demonstrated that the metabolite 5Ј-AMP can induce mice to undergo transient hypometabolism with T b as low as 26°C, similar to a torpor-like state (5). The T b of animals in torpor is defined to be at or moderately below 31°C (6). Here, we demonstrate tha...

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“…Energy homeostasis in a living organism is maintained by regulation of systemic metabolism. The role of erythrocytes in regulation of systemic metabolic control is well recognized, as illustrated by artificially boosting the number of erythrocytes in circulation, widely known as blood doping, to enhance athletic performance 25 26 , or by the induction of hypothermia through blood loss by exsanguination 27 28 . In our previous studies we have proposed that the adenylate equilibrium was perturbed upon an acute uptake of AMP by erythrocytes leading to systemic metabolic repression 23 .…”

Section: Discussionmentioning

confidence: 99%

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity

O’Brien

Berka

Tsai

et al. 2015

Sci Rep

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Erythrocytes are the key target in 5′-AMP induced hypometabolism. To understand how regulation of endogenous erythrocyte AMP levels modulates systemic metabolism, we generated mice deficient in both CD73 and AMPD3, the key catabolic enzymes for extracellular and intra-erythrocyte AMP, respectively. Under physiological conditions, these mice displayed enhanced capacity for physical activity accompanied by significantly higher food and oxygen consumption, compared to wild type mice. Erythrocytes from Ampd3−/− mice exhibited higher half-saturation pressure of oxygen (p50) and about 3-fold higher levels of ATP and ADP, while they maintained normal 2,3-bisphosphoglycerate (2,3-BPG), methemoglobin levels and intracellular pH. The affinity of mammalian hemoglobin for oxygen is thought to be regulated primarily by 2,3-BPG levels and pH (the Bohr effect). However, our results show that increased endogenous levels of ATP and ADP, but not AMP, directly increase the p50 value of hemoglobin. Additionally, the rise in erythrocyte p50 directly correlates with an enhanced capability of systemic metabolism.

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Exsanguination Cooling

Cited by 3 publications

References 3 publications

AMP Deaminase 3 Deficiency Enhanced 5′-AMP Induction of Hypometabolism

AMP Deaminase 3 Deficiency Enhanced 5′-AMP Induction of Hypometabolism

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals

CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity

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