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Splanchnic Circulation and Blood Pressure Regulation

内脏循环和血压调节

基本信息

批准号：
9253102
负责人：
Italo Biaggioni
金额：
$ 39.5万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9253102
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（由申请人提供）：内脏电容对血压调节的重要性早已被认识到，但由于实验方法的局限性，临床研究滞后。我们已经组建了一个研究团队（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），可以获得独特的资源（用trimethaphan进行神经节阻滞，用核医学和阻抗确定节段体积变化，自主神经功能衰竭患者），以在这一领域取得进展。动物研究的大量证据表明，内脏循环有助于高血压。我们对高血压患者的初步研究表明，曲美沙芬交感神经撤退通过减少每搏输出量降低血压。这表明交感神经介导的内脏电容收缩有助于人类高血压，我们将在特定目标1中检验这一假设。另一方面，内脏电容的反射性收缩是在直立姿势或热应激等刺激下维持足够血压的重要代偿机制。自主神经功能衰竭的患者缺乏这些代偿反射，并提供了一个独特的资源来研究这些现象。例如，在一个示例中，自主神经衰竭患者对热应激敏感，因为他们不能散热或不能用反射交感神经激活进行补偿。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性热应用来治疗自主神经功能衰竭的仰卧位高血压。最后，自主神经功能衰竭的临床表现主要是内脏静脉淤积引起的直立性低血压。我们开发了一种设备，可以检测直立姿势，并通过伺服控制器自动为腹带充气，将充气压力保持在40 mm Hg。我们的初步研究结果表明，这种自动腹带与米多君一样有效，米多君是目前提高立位耐力的标准治疗。我们将在Specific Aim 3中测试该器械的有效性。