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.

描述（申请人提供）：内脏电容对血压调节的重要性早已被认识到，但由于实验方法的限制，临床研究一直滞后。我们组建了一个研究小组（由生理学家、临床药理学家、心脏病学家、生物医学工程师和统计学家）能够获得独特的资源（用三甲芬进行神经节阻断、用核医学和阻抗确定节段体积变化、自主神经衰竭患者）以取得进展该领域的大量证据表明，内脏循环会导致高血压。我们对高血压受试者的初步研究表明，三甲芬可通过减少每搏输出量来降低交感神经收缩，从而导致高血压。在人类中，我们将在具体目标 1 中测试这一假设。另一方面，内脏电容的反射性收缩是维持充足血液的重要代偿机制自主神经衰竭患者缺乏这些代偿反射，并为研究这些现象提供了独特的资源，例如，自主神经衰竭患者对热应激敏感，因为他们无法散发热量或进行代偿。在具体目标 2 中，我们将利用这些异常来确定是否可以使用控制热应用来治疗自主神经衰竭的仰卧位高血压。最后，自主神经衰竭的临床表现以直立性低血压为主。我们开发了一种装置，可检测直立姿势并通过伺服控制器自动对腹部固定器充气，将充气压力维持在 40 毫米汞柱。我们的初步结果表明，这种自动腹部固定器与米多君一样有效。我们将在特定目标 3 中测试该设备的功效。