Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.
Advancing respiratory-cardiovascular physiology with the working heart-brainstem preparation over 25 years.
复制标题
DOI：
10.1113/jp281953
复制
发表时间：
2022-05
影响因子：
5.5
通讯作者：
St-John, Walter M.
中科院分区：
文献类型：
--
作者：
Paton, Julian F. R.;Machado, Benedito H.;Moraes, Davi J. A.;Zoccal, Daniel B.;Abdala, Ana P.;Smith, Jeffrey C.;Antunes, Vagner R.;Murphy, David;Dutschmann, Mathias;Dhingra, Rishi R.;McAllen, Robin;Pickering, Anthony E.;Wilson, Richard J. A.;Day, Trevor A.;Barioni, Nicole O.;Allen, Andrew M.;Menuet, Clement;Donnelly, Joseph;Felippe, Igor;St-John, Walter M.
关键词：
25年前，一种名为工作心-脑干准备（WHBP）的新生理准备被引入，声称它将提供一个新的平台，允许在心血管、神经内分泌、自主神经和呼吸研究中进行以前不可能进行的研究。在此，我们回顾了WHBP的一些进展，一些优点和缺点以及潜在的未来应用，并提供了用于准备的所有定制设备的照片和技术图纸。使用小鼠或大鼠，WHBP是一种原位实验模型，通过体外回路灌注，受益于前所未有的手术通道，全细胞记录的大脑机械稳定性以及类似于体外方法的不受损害的药物使用。该制备揭示了新的机制见解，例如，不同呼吸节律的产生，交感神经活动的神经发生，呼吸与心脏和循环之间的耦合，下丘脑和脊髓控制机制，以及外周和中枢化学受体机制。人们对高血压、心力衰竭和睡眠呼吸暂停等疾病有了更深入的了解。原位制备的发现已在有意识的体内动物中得到认可，并且在测试时已转化为人类。最后，我们讨论了WHBP潜在的未来应用，包括外周和中枢神经系统的双光子成像，以及药物遗传学工具的采用，这将提高我们对生理机制的理解，并揭示可能指导心肺疾病新治疗策略的新机制。工作心脏-脑干准备（WHBP）于1996年首次发表，从那时起揭示了呼吸节律和模式的产生，心脏和循环的自主控制以及呼吸系统和心血管系统耦合的生理相关性的新机制。本综述汇集了采用WHBP的国际作者队列，以强调使用这种原位动脉灌注制剂取得的一些主要进展和发现。
Twenty‐five years ago, a new physiological preparation called the working heart–brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advantages and disadvantages along with potential future applications, and provide photographs and technical drawings of all the customised equipment used for the preparation. Using mice or rats, the WHBP is an in situ experimental model that is perfused via an extracorporeal circuit benefitting from unprecedented surgical access, mechanical stability of the brain for whole cell recording and an uncompromised use of pharmacological agents akin to in vitro approaches. The preparation has revealed novel mechanistic insights into, for example, the generation of distinct respiratory rhythms, the neurogenesis of sympathetic activity, coupling between respiration and the heart and circulation, hypothalamic and spinal control mechanisms, and peripheral and central chemoreceptor mechanisms. Insights have been gleaned into diseases such as hypertension, heart failure and sleep apnoea. Findings from the in situ preparation have been ratified in conscious in vivo animals and when tested have translated to humans. We conclude by discussing potential future applications of the WHBP including two‐photon imaging of peripheral and central nervous systems and adoption of pharmacogenetic tools that will improve our understanding of physiological mechanisms and reveal novel mechanisms that may guide new treatment strategies for cardiorespiratory diseases. Abstract figure legend The working heart–brainstem preparation (WHBP) was first published in 1996 and since that time has revealed novel mechanisms in the generation of breathing rhythms and patterns, autonomic control of the heart and circulation, and the physiological relevance of the coupling between respiratory and cardiovascular systems. This review brings together an international cohort of authors who have adopted the WHBP, to highlight some of the major advances and discoveries made using this in situ arterially perfused preparation.
DOI：
10.1113/jphysiol.2014.270769
发表时间：
2014-05-15
期刊：
The Journal of physiology
影响因子：
--
作者：
Stalbovskiy AO;Briant LJ;Paton JF;Pickering AE
通讯作者：
Pickering AE