5-HT1A-agonist mediated recovery in hypovolemic shock

5-HT1A 激动剂介导低血容量休克的恢复

基本信息

批准号：
7185827
负责人：
KARIE E SCROGIN
金额：
$ 28.07万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-02-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7185827
关键词：
8-Hydroxy-2-(di-n-propylamino)tetralin Abate Acute Adrenergic Antagonists Adrenergic Receptor Agonist Angiotensin II Antihypertensive Agents Attenuated Bilateral Blood Blood Pressure Blood Vessels Bradycardia Buspirone Cardiac Output Cardiovascular system Cause of Death Cell Nucleus Cells Cessation of life Conscious Development Europe Exposure to Functional disorder Genes Heart Rate Hemorrhage Hypotension Hypovolemic Shock Infection Inflammation Infusion procedures Injection of therapeutic agent Ischemia Kidney Liquid substance Mediating Metabolic Morbidity - disease rate Nerve Neuraxis Nucleus solitarius Organ Outcome Patients Perfusion Peripheral Pharmaceutical Preparations Phase Rattus Receptor Activation Recovery Renal Blood Flow Reperfusion Injury Resuscitation Serotonin Serotonin Receptor 5-HT1A Shock Staging Sympatholytics Testing Therapeutic Tissues Trauma Vasoconstrictor Agents Venous alnespirone autonomic reflex crystalloid hemodynamics hindbrain improved kidney vascular structure method development pressure prevent receptor receptor expression response stem treatment planning

项目摘要

DESCRIPTION (provided by applicant): Trauma is the leading cause of death of young people in the U.S. (150,000/year). Most trauma deaths result either from insufficient tissue perfusion, due to excessive blood loss, or the development of inflammation, infection and end organ damage following resuscitation. Current treatment plans for hypovolemic shock rely on massive and rapid infusion of crystalloid fluids to raise cardiac output. It is now recognized that excessive volume resuscitation may increase blood loss and the reperfusion injury that contributes to the morbidity of hypovolemic shock. As such, the development of alternative strategies for the treatment of traumatic blood loss will be critical for the improvement of patient outcomes following hypovolemic shock; progressive hemorrhage produces a biphasic response. Increases in heart rate and sympathetic activity maintain blood pressure in the initial compensatory phase. These compensatory responses suddenly abate after significant blood loss (20-30%), resulting in hypotension, bradycardia and sympathoinhibition. We recently discovered that drugs that activate serotonin 5-HTIA receptors rapidly reverse the hypotensive and sympathoinhibitory responses to hemorrhage in conscious rats. Both central and systemic administration of 5-HTIA receptor agonists effectively raises blood pressure after either acute or sustained blood loss. These results indicate that 5-HTIA agonists could provide a promising therapy for hypovolemic shock. However, it is not known how 5-HTIA receptor activation increases arterial pressure or if the hemodynamic responses to agonist administration provide a beneficial effect on tissue perfusion. More importantly, it is not known if activation of 5-HTIA receptors can delay the transition from hypovolemic shock to circulatory collapse. Studies proposed in this project will determine the autonomic and hemodynamic effects of selective 5-HTIA agonists following sustained hypotensive hemorrhage to assess their impact on perfusion. Additional studies will assess the central nervous system mechanisms responsible for pressor effects of selective 5-HTIA agonists during hemorrhage. We will also assess the ability of clinically available 5-HT1A agonists to delay the transition from hypovolemic shock to circulatory collapse.

描述（由申请人提供）：创伤是美国年轻人死亡的主要原因（每年150,000）。大多数创伤死亡是由于失血过多而导致的组织灌注不足，或者复苏后炎症，感染和最终器官损伤的发展。当前的低血容量休克治疗计划依赖于大量和快速输注晶体液来提高心输出量。现在已经认识到，过量的量复苏可能会增加失血量和再灌注损伤，这导致低血容量减震的发病率。因此，开发治疗创伤性失血的替代策略对于改善低血容量减震后的患者结局至关重要。进行性出血产生双相反应。心率的增加和交感神经活动在初始补偿阶段保持血压。这些补偿性反应在大量失血后突然减轻（20-30％），导致低血压，心动过缓和交感神经抑制。我们最近发现，激活5-羟色胺5-HTIA受体的药物迅速扭转了对有意识大鼠出血的降低和交感抑制反应。 5-HTIA受体激动剂的中央和全身给药可有效地升高急性或持续失血后的血压。这些结果表明，5-HTIA激动剂可以为低血容量休克提供有希望的疗法。但是，尚不清楚5-HTIA受体激活如何增加动脉压，或者对激动剂给药的血液动力学反应是否对组织灌注产生了有益的作用。更重要的是，尚不清楚5-HTIA受体的激活是否会延迟从低血容量休克到循环崩溃的过渡。该项目中提出的研究将确定持续性低血压出血后选择性5-HTIA激动剂的自主和血液动力学作用，以评估其对灌注的影响。其他研究将评估导致选择性5-HTIA激动剂在出血期间的施加效应的中枢神经系统机制。我们还将评估临床上可用的5-HT1A激动剂延迟从低血液性休克到循环崩溃的过渡的能力。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock.

内脏区域的交感神经支配介导 8-OH-DPAT 在失血性休克中的有益血流动力学作用。

DOI：
10.1152/ajpregu.00689.2011
发表时间：
2012
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Tiniakov,Ruslan;Pahan,Kalipada;Scrogin,KarieE
通讯作者：
Scrogin,KarieE

The 5-hydroxytryptamine1A receptor agonist, (+)-8-hydroxy-2-(di-n-propylamino)-tetralin, increases cardiac output and renal perfusion in rats subjected to hypovolemic shock.

5-羟色胺1A 受体激动剂( )-8-羟基-2-(二正丙氨基)-四氢化萘可增加低血容量休克大鼠的心输出量和肾灌注。

DOI：
10.1124/jpet.106.114355
发表时间：
2007
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
0
作者：
Tiniakov,Ruslan;Osei-Owusu,Patrick;Scrogin,KarieE
通讯作者：
Scrogin,KarieE

Role of the arterial baroreflex in 5-HT1A receptor agonist-mediated sympathoexcitation following hypotensive hemorrhage.

动脉压力反射在低血压出血后 5-HT1A 受体激动剂介导的交感兴奋中的作用。

DOI：
10.1152/ajpregu.00671.2005
发表时间：
2006
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Osei-Owusu,Patrick;Scrogin,Karie
通讯作者：
Scrogin,Karie

The serotonin 5-Hydroxytryptaphan1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, stimulates sympathetic-dependent increases in venous tone during hypovolemic shock.

血清素 5-羟色氨酸 1A 受体激动剂 ( )8-羟基-2-(二正丙氨基)-四氢萘，在低血容量休克期间刺激交感神经依赖性静脉张力增加。

DOI：
10.1124/jpet.106.108944
发表时间：
2006
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
0
作者：
Tiniakov,Ruslan;Scrogin,KarieE
通讯作者：
Scrogin,KarieE

The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat.

大鼠失血性休克期间，5-HT1A 受体激动剂介导的平均循环充盈压增加需要脾脏。

DOI：
10.1152/ajpregu.91055.2008
发表时间：
2009
期刊：
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子：
0
作者：
Tiniakov,Ruslan;Scrogin,KarieE
通讯作者：
Scrogin,KarieE