A New Device to Mimic Intermittent Hypoxia in Mice

Kamil J Chodzyński,Alexandre Legrand,Myriam Kerkhofs,Luc Vanhamme,Alain Van Meerhaeghe,Karim Zouaoui Boudjeltia,Michel Vanhaeverbeek,Pierre Van Antwerpen,Gregory Coussement,Stephanie Conotte,J L Legros

doi:10.1371/journal.pone.0059973

Abstract

Intermittent hypoxia (hypoxia-reoxygenation) is often associated with cardiovascular morbidity and mortality. We describe a new device which can be used to submit cohorts of mice to controlled and standardised hypoxia-normoxia cycles at an individual level. Mice were placed in individual compartments to which similar gas flow parameters were provided using an open loop strategy. Evaluations made using computational fluid dynamics were confirmed by studying changes in haemoglobin oxygen saturation in vivo. We also modified the parameters of the system and demonstrated its ability to generate different severities of cyclic hypoxemia very precisely, even with very high frequency cycles of hypoxia-reoxygenation. The importance of the parameters on reoxygenation was shown. This device will allow investigators to assess the effects of hypoxia–reoxygenation on different pathological conditions, such as obstructive sleep apnoea or chronic obstructive pulmonary disease.

Highlights

Hypoxia-reoxygenation is a process whereby phases of low tissue oxygen pressure alternate with phases of normal tissue oxygen pressure. This phenomenon is associated with pathological conditions, such as myocardial infarction, stroke, cardiac arrest or septic shock [1,2]
When coupled with abrupt reoxygenation, hypoxia is associated with oxidative stress and an inflammatory response, which have multiple cardiovascular, neurocognitive and metabolic sequelae [4,5]
We describe a new device in which mice can be kept in individual compartments and submitted to similar standardised and controlled air-flow conditions, mimicking those found in clinical conditions

Summary

Introduction

Hypoxia-reoxygenation ( referred to as intermittent hypoxia [IH]) is a process whereby phases of low tissue oxygen pressure (hypoxia) alternate with phases of normal tissue oxygen pressure (normoxia). This phenomenon is associated with pathological conditions, such as myocardial infarction, stroke, cardiac arrest or septic shock [1,2]. Respiratory disorders, such as obstructive sleep apnoea (OSA) or central sleep apnoea, are characterised by repeated bouts of hypoxia [3]. The molecular mechanisms supporting such pathophysiological effects remain incompletely understood in vivo

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