ISSN: 2455-3476

Global Journal of Anesthesiology

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Oxygen Aspects on Sensing and Utilization

Sten GE1 and Moriyama T2*

1Section of Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute SE-171 77, Stockholm, Sweden
2Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, Sakuragaoka 8-35-1 Kagoshima, Japan

Author and article information

*Corresponding author: Dr. Takahiro Moriyama, Department of Anesthesiology and Intensive Care, Kagoshima University Hospital, Sakuragaoka 8-35-1 Kagoshima, Japan, Tel: +81-99-275-5430; Fax: +81-99-265-1642; Email: [email protected]
doi : 10.17352/2455-3476.000010
Submitted: 08 April, 2015 | Accepted: 22 April, 2015 | Published: 24 April, 2015
Keywords: Oxygen sensing; HIF-1; Potassium channel; Thermogenesis; Oxygen consumption

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Sten GE, Moriyama T (2015) Oxygen Aspects on Sensing and Utilization. Glob J Anesth. 2015; 2(1): 14-18. Available from: 10.17352/2455-3476.000010

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© 2015 Sten GE, et al. 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 author and source are credited.

Abstract

Oxygen is known to be one of the strongest electron acceptors and has one of its main functions in the electron transport chain producing ATP and heat, so important for energy expenditure and thermoregulation. However, some important mechanisms of oxygen functions are not completely delineated, yet. Sensing oxygen is purposeful and serves various specific functions. One mode of action is to initiate afferent neuronal activity which requires increased cytosolic Ca2+ concentrations. Another action is linked to the Hypoxia Inducible Factor, HIF-1, which in the normoxic state is produced in a prolyl-hydroxylase regulated reaction. The calcium generated neuronal response is usually described as a quick, acute, response that is set in action within seconds whereas the HIF related responses are slower, chronic, activated after several minutes to hours. Traditionally, it has been the opinion that oxygen can diffuse freely across plasma membranes. However, the lipid bilayer has higher viscosity than water by several times, and high oxygen permeability has not been proven. Hence, oxygen transportation across plasma or cell membranes cannot be explained by diffusion alone. It is therefore justified to ask the question if a specific oxygen channel or transport mechanism remains to be discovered.

Indexing and Abstracting

Introduction

Oxygen is vital for life and plays a key role for the physiological homeostasis of the human body. It is known to be one of the strongest electron acceptors and has one of its main functions in the electron transport chain producing adenosine 5'-triphosphate (ATP) and heat, so important for energy expenditure and thermoregulation. Yet, some important mechanisms of oxygen functions are not completely delineated and oxygen research is an active scientific field in basic medical research, experimental investigations as well as in clinical research. In clinical medicine both hyperoxia and hypoxia are in focus. This presentation will mainly be dealing with reactions to low oxygen tensions.

There is a well-balanced sensory function to maintain oxygen tension in blood within narrow margines. The normal but small oxygen variations in blood are sufficient to trigger activities in the carotid body in order to create afferent impulses via the sinus nerve and the IXth cranial nerve to the central nervous system. Together with pH variations or carbo dioxide (CO2), oxygen is an important factor for regulation of breathing.

In this communication some of the most highlighted mechanisms for the sensing of low oxygen tensions will be discussed and opinions on oxygen utilization will be presented with regard to plasma membrane passage of oxygen and intracellular electron transport. In addition, effects of different anesthetic agents on oxygen sensing and utilization will be commented upon.

Oxygen Sensing

Oxygen is sensed by most mammalian cells. Glomus cells in the carotid body, neuroepithelial body cells in the airways, smooth muscle cells in the systemic or pulmonary circulation, and chromaffin cells have been reported as typical cells having specific oxygen sensing capacities. In 1995, Wang, Semenza et al. discovered the hypoxia inducible factor 1 (HIF-1) as a key oxygen regulator in mammalian cells [3]. Hence, both calcium and HIF based mechanisms are most prominent for protective reactions against low oxygen tensions. The calcium generated neuronal response is usually described as a quick, acute, response that is set in action within seconds whereas HIF related responses are slower, chronic, activated after several minutes to hours [3] (Figure 1).

Ca2+ related Oxygen sensing

Until the discovery of HIF-1, in 1995, research on oxygen sensing mechanisms has mainly been conducted with focus on physiological responses to acute hypoxia, as hypoxia induces critical damages in tissues and organs and jeopardizes physiological homeostasis. There are different mechanisms to accomplish the acute, calcium mediated, oxygen sensing. One of them, as described by Lopez-Barneo and colleagues [7],[10]. In addition, it is also known that propofol and neuromuscular blocking agents prevent chemoreceptor activity in the carotid body [11]-[1] who discovered HIF-1 and Ratcliff et al. who described the importance of prolyl hydroxylation [[16]. During hypoxia, the prolyl-hydroxylation is inhibited and HIF-1α accumulates. It is most likely so that all nucleotide cells in the body can sense and respond to hypoxia via this mechanism.

As pointed out above this is a fairly slow responding system that takes minutes to hours. HIF-1 regulates the expression of more than hundred genes that mediate important adaptive physiological responses such as angiogenesis, erythropoiesis, and glycolysis [[19]-[22]. However, the lipid bilayer has higher viscosity than water by several times, and high oxygen permeability has not been proven. In model experiments using biological monolayer membranes, it was shown that oxygen permeability is lower than previously reported [[24], and 13 isoforms (AQP0-12) have since been identified in humans. Among them, AQP 1, 2, 4, and 5 are primarily aquaporins, and some of them have function also as gas channels. It is especially AQP1 that have been reported as a gas channel, transporting CO2 and nitric oxide (NO) across the plasma membrane [25]. The investigators measured the rate of cellular acidification caused by CO2 influx across the cell membrane using intracellular electrodes.

Concerning oxygen, Jose Lopez-Barneo et al. showed, in 2007 [[27]. In support of such a suggestion, Ivanov II et al. reported that the two AQP channel blockers, mercury chloride (HgCl2) and p-chloromercuribenzoate (PCMB), dose-dependently inhibited oxygen absorption by erythrocytes [31].

During the latest few years it has been proven that brown adipose tissue is also present and have an active function in adult humans. Positron emission tomography- computed tomography (PET-CT) investigations showed, in adult humans, a high uptake of 18F-FDP in the neck, in the supraclavicular region, and at classical locations for brown adipose tissue in para-aortic and paravertebral areas as well as suprarenally indicating the existence of brown adipose tissue also in adults [38]. It is also known that volatile anesthetic agents inhibit heat production, oxygen consumption, in studies of animals and infants known to have brown adipose tissue [[41]. It is likely that not only neonates and infants but also adults with brown adipose tissue will have a disturbed temperature balance during long duration surgery most likely, at least partly, due to effects on oxygen consumption in brown adipose tissue. The area is indeed open for further important clinical studies during anesthesia.

Amino acid –induced thermogenesis

It has for a long time been a dogma that amino acids during anesthesia and surgery do not contribute to heat production and recovery. Sellden et al. reported, in 1994, that amino acids induced thermogenesis and diminished hypothermia under general anesthesia [[43]. In the same series of investigations it was also reported that this thermogenetic effect occurred in extra-splanchnic tissues and that it was not associated with stress response [41]. In one study it was reported that amino-acid infusions during general anesthesia increased plasma insulin concentrations and systemic oxygen consumption [47,49]-[52],53]. Many studies have reported the efficacy of H2S in animal experiments using rodent models, whereas other studies failed to show the effects, especially in larger animal models such as piglets and sheep. For future clinical applications, there are many questions that will have to be answered. It will be most interesting to follow the development of this scientific field with the goals to find correct indications for the use of H2S, to work out therapeutic strategies and to rule out possible side effects.

In conclusion, supplying oxygen to tissues or organs is one of the most important treatments of patients in particular during surgery or critical conditions. However, in these situations, several factors like as inflammatory, oxidative stress, activation of sympathetic nerve system and renin angiotensin system disturb the balance between oxygen demand and supply. Clinicians need to recognize the mechanism of oxygen sensing, oxygen transport, and oxygen utility in the cells to maintain the homeostasis of patients in clinical conditions.

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