Cardiorespiratory Afferent Control in Heart Failure

Research project

Description

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.
StatusFinished
Effective start/end date4/1/053/31/10

Funding

  • National Institutes of Health: $253,876.00
  • National Institutes of Health: $261,459.00
  • National Institutes of Health: $267,750.00
  • National Institutes of Health: $253,876.00

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Heart Failure
Lung
N-Methyl-D-Aspartate Receptors
Rodentia
Neurons
Sensory Feedback
Continuous Positive Airway Pressure
Vagotomy
GABA-A Receptors
Brain Stem
Ventilation
Respiration
Gases
Blood Pressure
Morbidity
Messenger RNA
Mortality
Health

Keywords

  • Medicine(all)