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Cardiac afferents and renal function in heart failure

心力衰竭中的心脏传入和肾功能

基本信息

批准号：
10084301
负责人：
Hanjun Wang
金额：
$ 57.17万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-18 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10084301
关键词：
Ablation Acute myocardial infarction Affect Afferent Neurons American Capsaicin Cardiac Cardiac Output Cardiovascular Diseases Cardiovascular system Cells Central venous pressure Chest Chronic Clinical Complication Congestive Congestive Heart Failure Conscious Coupled Data Denervation Development Diagnosis Diastolic blood pressure Epidemic Exhibits Functional disorder Grant Heart Heart Injuries Heart failure Hypothalamic structure Injury to Kidney Kidney Kidney Failure Laboratories Left Low Cardiac Output Measures Mediating Medical Metabolic Modeling Morbidity - disease rate Myocardial Infarction Nerve Neural Pathways Neurons Neurotoxins Pathogenesis Pathway interactions Patients Plasma Play Prognosis Progressive Disease Rattus Reflex action Reflex control Renal Blood Flow Renal function Renin-Angiotensin-Aldosterone System Resiniferatoxin Rodent Model Role Sensory Societies Spinal Spinal Ganglia Syndrome TRPV1 gene Techniques Testing Therapeutic Thinking Transgenic Organisms United States Vascular resistance Vasoconstrictor Agents Vasopressins Venous Venous Pressure level Ventricular Work analog base conventional therapy cytokine designer receptors exclusively activated by designer drugs hemodynamics hypoperfusion improved innovation kidney dysfunction kidney vascular structure magnocellular mortality novel novel therapeutics paraventricular nucleus prevent receptor relating to nervous system renal ischemia systemic inflammatory response therapy development vasoconstriction

项目摘要

Project Summary Chronic heart failure (CHF) is a growing epidemic in western societies. In the United States alone, approximately 6 million people live with CHF. In late stage CHF, renal failure is a complication that results in worsening heart failure. Patients exhibiting the cardio-renal syndrome have an extremely poor prognosis. Medical therapy for this syndrome has been ineffective. A new way of thinking about the mechanisms responsible for worsening renal function in CHF is necessary. During the previous cycle of this grant we elucidated an important neural pathway that not only mediates cardiac remodeling but also drives a massive increase in cardiac, renal and global sympathetic nerve activity in CHF. Ablation of this pathway markedly improves survival in the post MI-CHF rodent model. The Cardiac Sympathetic Afferent Reflex (CSAR) is mediated, in large part, by epicardial, TRPV1 receptor-expressing sensory endings whose cell bodies reside in the thoracic dorsal root ganglia. Here, we propose to build on our previous work by demonstrating an important role for cardiac spinal afferents in mediating renal dysfunction in severe CHF. Based on our preliminary data and using a novel TRPV1 Cre rat coupled with chemogenetic excitation and inhibition we will demonstrate the important role that these afferents play in the pathogenesis of the cardio-renal syndrome. We will furthermore utilize the ultrapotent neurotoxin resiniferatoxin (RTX; TRPV1 specific) to therapeutically salvage renal function in CHF. These studies are highly relevant to the clinical situation and will pave the way for a novel and innovative alternative to conventional therapy.

项目总结