权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Splanchnic Circulation and Blood Pressure Regulation

内脏循环和血压调节

基本信息

批准号：
9542936
负责人：
Italo Biaggioni
金额：
$ 4.11万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9542936
关键词：
Abdomen Affect Animal Model Animals Antihypertensive Agents Automobile Driving Baroreflex Beds Biomedical Engineering Blood Blood Pressure Blood Vessels Blood Volume Buffers Cardiac Output Cardiovascular system Chest Clinical Clinical Research Denervation Development Devices Diabetes Mellitus Discipline of Nuclear Medicine Disease Diuresis Economic Inflation Electric Capacitance Erythrocytes Failure Frail Elderly Ganglia General Population Heat Stress Disorders Human Hypertension Label Maintenance Measures Mechanics Mediating Methodology Methods Midodrine Modeling Nerve Operative Surgical Procedures Orthostatic Hypotension Patient Rights Patients Pharmacology Pharmacotherapy Play Posture Radioisotopes Reflex action Regulation Research Residual state Resistant Hypertension Resources Rest Risk Factors Role Splanchnic Circulation Stimulus Stroke Volume Supination Sympathetic Nervous System Technetium Testing Trimethaphan Vascular resistance Venous Withdrawal autonomic neuropathy blood pressure reduction blood pressure regulation clinical translation common treatment disability effective intervention effective therapy efficacy testing electric impedance falls hemodynamics improved mortality nerve supply neuroregulation novel strategies patient population pressure prevent public health relevance response standard of care vasoconstriction

项目摘要

DESCRIPTION (provided by applicant): The importance of splanchnic capacitance to blood pressure regulation has long been recognized, but clinical research has lagged behind because of limitations in experimental methodology. We have put together a research team (of physiologists, clinical pharmacologists, cardiologists, biomedical engineers and statisticians) with access to unique resources (ganglionic blockade with trimethaphan, determination of segmental volume changes with nuclear medicine and impedance, patients with autonomic failure) to make progress in this field. Substantial evidence from animal studies indicates that the splanchnic circulation contributes to hypertension. Our preliminary studies in hypertensive subjects indicate that sympathetic withdrawal with trimethaphan lowers blood pressure by reducing stroke volume. This suggests that sympathetically mediated contraction of splanchnic capacitance contributes to hypertension in humans, a hypothesis that we will test in Specific Aim 1. On the other hand, reflex contraction of splanchnic capacitance is an important compensatory mechanism to maintain adequate blood pressure during stimuli such as upright posture or heat stress. Patients with autonomic failure lack these compensatory reflexes and provide a unique resource to study these phenomena. E.g., autonomic failure patients are sensitive to heat stress because they are unable to dissipate heat or to compensate with reflex sympathetic activation. In Specific Aim 2 we will take advantage of these abnormalities to determine if controlled heat application can be used to treat the supine hypertension of autonomic failure. Finally, the clinical picture of autonomic failure is dominated by orthostatic hypotension due primarily to splanchnic venous pooling. We have developed a device that detects upright posture and automatically inflates an abdominal binder with a servo controller that maintains inflation pressure to 40 mm Hg. Our preliminary results suggest that this automated abdominal binder is as effective as midodrine, the current standard of care in improving orthostatic tolerance. We will test the efficacy of this device in Specific Aim 3.