Cargando…
Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram
NEW FINDINGS: What is the central question of this study? The lack of useful small‐animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise‐induced ventilatory abnormalities in various disease states. What is the main finding and its impo...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032965/ https://www.ncbi.nlm.nih.gov/pubmed/29509982 http://dx.doi.org/10.1113/EP086850 |
_version_ | 1783337609219538944 |
---|---|
author | Miyamoto, Tadayoshi Manabe, Kou Ueda, Shinya Nakahara, Hidehiro |
author_facet | Miyamoto, Tadayoshi Manabe, Kou Ueda, Shinya Nakahara, Hidehiro |
author_sort | Miyamoto, Tadayoshi |
collection | PubMed |
description | NEW FINDINGS: What is the central question of this study? The lack of useful small‐animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise‐induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized‐rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. ABSTRACT: Exercise‐induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized‐rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath‐by‐breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end‐tidal CO(2) pressure ([Formula: see text]) and minute ventilation ([Formula: see text]), and the plant by the hyperbolic relationship between [Formula: see text] and [Formula: see text]. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity‐dependent changes in operating points ([Formula: see text] and [Formula: see text]) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized‐rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. |
format | Online Article Text |
id | pubmed-6032965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60329652018-07-12 Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram Miyamoto, Tadayoshi Manabe, Kou Ueda, Shinya Nakahara, Hidehiro Exp Physiol Research Papers NEW FINDINGS: What is the central question of this study? The lack of useful small‐animal models for studying exercise hyperpnoea makes it difficult to investigate the underlying mechanisms of exercise‐induced ventilatory abnormalities in various disease states. What is the main finding and its importance? We developed an anaesthetized‐rat model for studying exercise hyperpnoea, using a respiratory equilibrium diagram for quantitative characterization of the respiratory chemoreflex feedback system. This experimental model will provide an opportunity to clarify the major determinant mechanisms of exercise hyperpnoea, and will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. ABSTRACT: Exercise‐induced ventilatory abnormalities in various disease states seem to arise from pathological changes of respiratory regulation. Although experimental studies in small animals are essential to investigate the pathophysiological basis of various disease models, the lack of an integrated framework for quantitatively characterizing respiratory regulation during exercise prevents us from resolving these problems. The purpose of this study was to develop an anaesthetized‐rat model for studying exercise hyperpnoea for quantitative characterization of the respiratory chemoreflex feedback system. In 24 anaesthetized rats, we induced muscle contraction by stimulating bilateral distal sciatic nerves at low and high voltage to mimic exercise. We recorded breath‐by‐breath respiratory gas analysis data and cardiorespiratory responses while running two protocols to characterize the controller and plant of the respiratory chemoreflex. The controller was characterized by determining the linear relationship between end‐tidal CO(2) pressure ([Formula: see text]) and minute ventilation ([Formula: see text]), and the plant by the hyperbolic relationship between [Formula: see text] and [Formula: see text]. During exercise, the controller curve shifted upward without change in controller gain, accompanying increased oxygen uptake. The hyperbolic plant curve shifted rightward and downward depending on exercise intensity as predicted by increased metabolism. Exercise intensity‐dependent changes in operating points ([Formula: see text] and [Formula: see text]) were estimated by integrating the controller and plant curves in a respiratory equilibrium diagram. In conclusion, we developed an anaesthetized‐rat model for studying exercise hyperpnoea, using systems analysis for quantitative characterization of the respiratory system. This novel experimental model will be useful for understanding the mechanisms responsible for abnormal ventilatory responses to exercise in disease models. John Wiley and Sons Inc. 2018-04-30 2018-05-01 /pmc/articles/PMC6032965/ /pubmed/29509982 http://dx.doi.org/10.1113/EP086850 Text en © 2018 Morinomiya University of Medical Sciences. Experimental Physiology published by John Wiley and Sons Ltd on behalf of & The Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Papers Miyamoto, Tadayoshi Manabe, Kou Ueda, Shinya Nakahara, Hidehiro Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title | Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title_full | Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title_fullStr | Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title_full_unstemmed | Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title_short | Development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
title_sort | development of an anaesthetized‐rat model of exercise hyperpnoea: an integrative model of respiratory control using an equilibrium diagram |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032965/ https://www.ncbi.nlm.nih.gov/pubmed/29509982 http://dx.doi.org/10.1113/EP086850 |
work_keys_str_mv | AT miyamototadayoshi developmentofananaesthetizedratmodelofexercisehyperpnoeaanintegrativemodelofrespiratorycontrolusinganequilibriumdiagram AT manabekou developmentofananaesthetizedratmodelofexercisehyperpnoeaanintegrativemodelofrespiratorycontrolusinganequilibriumdiagram AT uedashinya developmentofananaesthetizedratmodelofexercisehyperpnoeaanintegrativemodelofrespiratorycontrolusinganequilibriumdiagram AT nakaharahidehiro developmentofananaesthetizedratmodelofexercisehyperpnoeaanintegrativemodelofrespiratorycontrolusinganequilibriumdiagram |