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      The physiology of artificial hibernation

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          Abstract

          Incomplete understanding of the mechanisms responsible for induction of hibernation prevent translation of natural hibernation to its artificial counterpart. To facilitate this translation, a model was developed that identifies the necessary physiological changes for induction of artificial hibernation. This model encompasses six essential components: metabolism (anabolism and catabolism), body temperature, thermoneutral zone, substrate, ambient temperature, and hibernation-inducing agents. The individual components are interrelated and collectively govern the induction and sustenance of a hypometabolic state. To illustrate the potential validity of this model, various pharmacological agents (hibernation induction trigger, delta-opioid, hydrogen sulfide, 5’-adenosine monophosphate, thyronamine, 2-deoxyglucose, magnesium) are described in terms of their influence on specific components of the model and corollary effects on metabolism.

          Relevance for patients: The ultimate purpose of this model is to help expand the paradigm regarding the mechanisms of hibernation from a physiological perspective and to assist in translating this natural phenomenon to the clinical setting.

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          Most cited references152

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          Body size and metabolism

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            Hibernation versus Daily Torpor in Mammals and Birds: Physiological Variables and Classification of Torpor Patterns

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              3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone.

              Thyroxine (T(4)) is the predominant form of thyroid hormone (TH). Hyperthyroidism, a condition associated with excess TH, is characterized by increases in metabolic rate, core body temperature and cardiac performance. In target tissues, T(4) is enzymatically deiodinated to 3,5,3'-triiodothyronine (T(3)), a high-affinity ligand for the nuclear TH receptors TR alpha and TR beta, whose activation controls normal vertebrate development and physiology. T(3)-modulated transcription of target genes via activation of TR alpha and TR beta is a slow process, the effects of which manifest over hours and days. Although rapidly occurring effects of TH have been documented, the molecules that mediate these non-genomic effects remain obscure. Here we report the discovery of 3-iodothyronamine (T(1)AM), a naturally occurring derivative of TH that in vitro is a potent agonist of the G protein-coupled trace amine receptor TAR1. Administering T(1)AM in vivo induces profound hypothermia and bradycardia within minutes. T(1)AM treatment also rapidly reduces cardiac output in an ex vivo working heart preparation. These results suggest the existence of a new signaling pathway, stimulation of which leads to rapid physiological and behavioral consequences that are opposite those associated with excess TH.
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                Author and article information

                Journal
                J Clin Transl Res
                J Clin Transl Res
                Whioce Publishing Pte. Ltd.
                Journal of Clinical and Translational Research
                Whioce Publishing Pte. Ltd.
                2382-6533
                2424-810X
                30 September 2015
                30 September 2015
                : 1
                : 2
                : 78-93
                Affiliations
                Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
                Author notes

                * Corresponding author: Marcel C. Dirkes, MD, Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands, Tel: +31 20 5665568. E-mail: Dirkes@ 123456mac.com

                Article
                jctres.201502.005
                6410623
                1e08be3f-b352-4d69-8379-d92fbcaeb629
                Copyright © 2015, Whioce Publishing Pte. Ltd.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 5 May 2015
                : 7 September 2015
                : 14 September 2015
                Categories
                Medical Hypothesis

                anapyrexia,hypometabolic agents,hypometabolism,natural hibernation,torpor,thermoneutral zone,hypoxia,body temperature,thermal convection,arrhenius law

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