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）是死亡率的主要原因，与打蜡和减弱的呼吸模式以及对血液气体的敏感性增强，但对血压的敏感性降低。经过连续气道压力治疗的患者不仅可以改善通风，而且出乎意料的是心肌功能。我们的长期目标是了解对心血管和呼吸功能（心肺耦合）的协调控制。使用HF，肺部，巴罗 - 和化学感官反馈的庞蒂定调节丧失可能是交感神经呼吸的合并症的基础。我们的具体目的是：1）确定激活肺伸展运动，巴罗和化学受体受体对交感神经和呼吸运动模式和耦合的影响神经元和3）确定蓬托Gabaergic和NMDA受体在介导这些传入对正常和HF动物中心肺偶联的影响中的作用。为了解决这些目标，我们提出了一种提供新颖能力和协同作用的协作方法。 PI将研究正常和HF啮齿动物模型中交感呼吸耦合的神经机制。 HF啮齿动物菌落将由Hoit博士维持，Hoit博士还将评估HF大鼠的心脏功能（AIMS 1和3）。 Siegel博士将表征Pontine Gabaa和NMDA受体亚基mRNA表达，亚型形成和定位（AIM 3）。在USF的Morris博士的情况下，PI将分析脑干神经元及其对迷走神经切开术前后对化学和巴罗症的反应（AIM 2）。这些研究将证明传入输入的桥丁调节在确定有关健康和HF中交感呼吸性节奏的肺，巴罗和化学感官信息中的作用。

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.