Cardiorespiratory Afferent Control in Heart Failure

心力衰竭的心肺传入控制

• 批准号: 7214176
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214176
• 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，与呼吸模式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改善了通气，而且意外地改善了心肌功能。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HF，肺、压力和化学感觉反馈的脑桥条件反射的丧失可能是交感-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HF中如何改变，2）确定这些感觉输入在形成腹外侧延髓和背外侧脑桥神经元的交感神经和脉搏相关活动的幅度和一致性中的相互作用，（3）在正常和HF动物中，研究桥脑GABA能和NMDA受体在介导这些传入对心肺耦联的影响中的作用。为了实现这些目标，我们提出了一种协作方法，提供新的能力和协同作用。PI将研究正常和啮齿动物HF模型中交感神经-呼吸耦合的神经机制。HF啮齿动物群将由Dr. Hoit维护，他还将评估HF大鼠的心脏功能（目的1和3）。Siegel博士将描述脑桥GABAA和NMDA受体亚单位mRNA表达、亚型形成和定位（目标3）。与USF的Morris博士一起，PI将分析脑干神经元及其在迷走神经切断术前后对化学和压力传入刺激的反应（目标2）。这些研究将证明脑桥传入输入条件反射在确定肺、气压和化学感觉信息对健康和HF中交感呼吸节律的影响中的作用。