Miyamoto Tadayoshi, Manabe Kou, Ueda Shinya, Nakahara Hidehiro
Graduate School of Health Sciences, Morinomiya University of Medical Sciences, Osaka City, Osaka, 559-0034, Japan.
Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center Research Institute, Suita City, Osaka, 565-8565, Japan.
Exp Physiol. 2018 May 1;103(5):748-760. doi: 10.1113/EP086850.
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.
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 pressure (P ETC O2) and minute ventilation (V̇E), and the plant by the hyperbolic relationship between V̇E and P ETC O2. 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 (V̇E and P ETC O2) 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.
本研究的核心问题是什么？缺乏用于研究运动性呼吸急促的实用小动物模型使得难以探究各种疾病状态下运动诱发的通气异常的潜在机制。主要发现及其重要性是什么？我们开发了一种用于研究运动性呼吸急促的麻醉大鼠模型，使用呼吸平衡图对呼吸化学反射反馈系统进行定量表征。该实验模型将为阐明运动性呼吸急促的主要决定机制提供机会，并有助于理解疾病模型中运动通气异常反应的机制。
各种疾病状态下运动诱发的通气异常似乎源于呼吸调节的病理变化。尽管在小动物身上进行实验研究对于探究各种疾病模型的病理生理基础至关重要，但缺乏一个用于定量表征运动期间呼吸调节的综合框架阻碍了我们解决这些问题。本研究的目的是开发一种用于研究运动性呼吸急促的麻醉大鼠模型，以对呼吸化学反射反馈系统进行定量表征。在24只麻醉大鼠中，我们通过在低电压和高电压下刺激双侧坐骨神经远端来诱导肌肉收缩以模拟运动。在运行两个方案以表征呼吸化学反射的控制器和受控对象时，我们记录了逐次呼吸的呼吸气体分析数据和心肺反应。通过确定呼气末二氧化碳分压（PETCO₂）与分钟通气量（VE）之间的线性关系来表征控制器，通过VE与PETCO₂之间的双曲线关系来表征受控对象。运动期间，随着摄氧量增加，控制器曲线向上移动而控制器增益不变。双曲线型的受控对象曲线根据运动强度向右下方移动，这与代谢增加的预测一致。通过在呼吸平衡图中整合控制器和受控对象曲线来估计运动强度依赖性的工作点（VE和PETCO₂）变化。总之，我们开发了一种用于研究运动性呼吸急促的麻醉大鼠模型，使用系统分析对呼吸系统进行定量表征。这种新颖的实验模型将有助于理解疾病模型中运动通气异常反应的机制。
