Cardiorespiratory Afferent Control in Heart Failure

心力衰竭的心肺传入控制

• 批准号: 7388833
• 负责人: THOMAS E DICK
• 金额: $ 25.39万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7388833
• 关键词: Address; American; Animal Model; Animals; Arrhythmia; Blood Pressure; Blood gas; Brain Stem; Brain region; Breathing; Cardiac; Cardiac Output; Cardiovascular system; Chemoreceptors; Cheyne-Stokes Respiration; Continuous Positive Airway Pressure; Coupled; Coupling; Data; Diagnosis; Electrodes; Environmental air flow; Exhibits; Feedback; Felis catus; Goals; Health; Heart failure; Intervention; Lateral; Lead; Left Ventricular Dysfunction; Life; Lung; Mediating; Modality; Morbidity - disease rate; Motor; Motor Activity; Myocardial; N-Methyl-D-Aspartate Receptors; Nature; Nerve; Neurons; Neurotransmitters; Oxygen; Patients; Pattern; Peripheral; Personal Satisfaction; Physiologic pulse; Physiological; Polymerase Chain Reaction; Pontine structure; Pressoreceptors; Process; Protein Isoforms; Pulmonary Stretch Receptors; Pulse taking; Rattus; Reflex action; Research Personnel; Respiration; Respiratory physiology; Rodent; Rodent Model; Role; Sensory; Shapes; Stretching; Stroke Volume; System; Technology; Testing; Vagotomy; Venous; Waxes; conditioning; improved; mRNA Expression; mortality; neuromechanism; novel; programs; receptor; receptor expression; respiratory; response; sensory feedback; synergism

DESCRIPTION (provided by applicant): Heart failure (HF) is a leading cause of mortality and is associated with a waxing and waning breathing pattern as well as enhanced sensitivity to blood gases but decreased sensitivity to blood pressure. Patients treated with continuous positive airway pressure not only have improved ventilation but also, unexpectedly, myocardial function. Our long-term goal is to understand the coordinated control of cardiovascular and respiratory function (cardiorespiratory coupling). With HF, the loss of pontine conditioning of pulmonary, baro- and chemo-sensory feedback may underlie the sympatho-respiratory co-morbidities. Our Specific Aims are: 1) To determine the influence of activating pulmonary stretch-, baro-and chemo-receptors, on sympathetic and respiratory motor patterns and coupling, and to determine how these influences are altered in HF, 2) To determine the interaction between these sensory inputs in shaping the magnitude and consistency of respiratory-and pulse-correlated activities of ventrolateral medullary and dorsolateral pontine neurons, and 3) To determine the role of pontine GABAergic and NMDA receptors in mediating the effect of these afferents on cardiorespiratory coupling in normal and HF animals. To address these Aims, we propose a collaborative approach that offers novel capabilities and synergisms. The PI will study neural mechanisms of sympatho-respiratory coupling in normal and a rodent model of HF. The HF rodent colony will be maintained by Dr. Hoit, who will also assess cardiac function in HF rats (Aims 1 & 3). Dr. Siegel will characterize pontine GABAA and NMDA receptor subunit mRNA expression, subtype formation and localization (Aim 3). With Dr. Morris at USF, the PI will analyze brainstem neurons and their responses to chemo- and baro-afferent stimulation before and after vagotomy (Aim 2). These studies will demonstrate the role of pontine conditioning of afferent input in determining the effect pulmonary, baro-and chemo-sensory information on sympatho-respiratory rhythm in health and in HF.

描述（由申请人提供）：心力衰竭 (HF) 是死亡的主要原因，与呼吸规律的起伏以及对血气的敏感性增强但对血压的敏感性降低有关。接受持续气道正压通气治疗的患者不仅通气得到改善，而且出乎意料的是，心肌功能也得到改善。我们的长期目标是了解心血管和呼吸功能的协调控制（心肺耦合）。对于心力衰竭，肺脑桥调节、压力和化学感觉反馈的丧失可能是交感呼吸共病的基础。我们的具体目标是：1) 确定激活肺牵张、压力和化学感受器对交感神经和呼吸运动模式和耦合的影响，并确定这些影响在心力衰竭中如何改变，2) 确定相互作用这些感觉输入在塑造腹外侧延髓和背外侧脑桥神经元的呼吸和脉搏相关活动的幅度和一致性方面之间的关系，以及 3) 确定脑桥的作用GABA 能和 NMDA 受体介导这些传入信号对正常和心力衰竭动物心肺耦合的影响。为了实现这些目标，我们提出了一种提供新颖功能和协同作用的协作方法。 PI 将研究正常心力衰竭和啮齿动物模型中交感呼吸耦合的神经机制。心力衰竭啮齿类动物群将由 Hoit 博士负责维护，他还将评估心力衰竭大鼠的心脏功能（目标 1 和 3）。 Siegel 博士将描述脑桥 GABAA 和 NMDA 受体亚基 mRNA 表达、亚型形成和定位的特征（目标 3）。 PI 将与南佛罗里达大学的 Morris 博士一起分析脑干神经元及其在迷走神经切断术前后对化学和气压传入刺激的反应（目标 2）。这些研究将证明脑桥调节传入输入在确定肺、气压和化学感觉信息对健康和心衰患者交感呼吸节律的影响方面的作用。

项目成果

Cardiorespiratory coupling: common rhythms in cardiac, sympathetic, and respiratory activities.

• DOI: 10.1016/b978-0-444-63274-6.00010-2
• 发表时间: 2014
• 期刊: PROGRESS IN BRAIN RESEARCH
• 作者: Dick, Thomas E.;Hsieh, Yee-Hsee;Dhingra, Rishi R.;Baekey, David M.;Galan, Roberto F.;Wehrwein, Erica;Morris, Kendall F.
• 通讯作者: Morris, Kendall F.

Effects of baroreceptor activation on respiratory variability in rat.

• DOI: 10.1016/j.resp.2009.02.006
• 发表时间: 2009-04-30
• 期刊: RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
• 影响因子: 2.3
• 作者: McMullan, Simon;Dick, Thomas E.;Farnham, Melissa M. J.;Pilowsky, Paul M.
• 通讯作者: Pilowsky, Paul M.