AUTOREGULATION OF CEREBRAL BLOOD FLOW IN ACUTE ISCHEMIA

急性缺血时脑血流的自动调节

• 批准号: 6795650
• 负责人: WILLIAM J POWERS
• 金额: $ 24.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6795650
• 关键词: acute disease /disorder; antihypertensive agents; blood pressure; brain disorder diagnosis; brain edema; cerebral hemorrhage; cerebral ischemia /hypoxia; clinical research; human subject; human therapy evaluation; magnetic resonance imaging; medical complication; neurologic manifestations; neuroregulation; outcomes research; pathologic process; positron emission tomography; relapse /recurrence; stroke; vascular resistance

Hypertension is one of the most significant risk factors for ischemic stroke. Long term treatment of hypertension after stroke has been shown to reduce the incidence of recurrent stroke by 28% and major cardiovascular complications by 26%. However, in the setting of acute ischemic stroke it has been difficult to determine the appropriate treatment of elevated blood pressure due to the overwhelming concern that lowering blood pressure in this setting might worsen cerebral ischemia. These concerns are based primarily on studies of CBF in animal models. Very few studies of the effect of pharmacological reduction of elevated blood pressure on CBF following acute ischemic stroke in humans have been done and they do not provide adequate data to settle this issue. The goal of this research project is to determine the effect of controlled, graded pharmacologic reduction of blood pressure on rCBF following acute ischemic stroke using positron emission tomography (PET) and to carefully monitor the clinical effects and safety of treatment. This specific null hypothesis will be tested: Pharmacological reduction of mean arterial blood pressure (MAP) by 15 +/- 5 mm Hg in patients with a recent cerebral infarction and elevated blood pressure does not produce a statistically significant reduction in regional cerebral blood flow. This Specific Aim will be carried out: Between day 3-14 after onset, sixty patients with a hemispheric cerebral infarction and mean arterial blood pressure of 120-150 mm Hg will undergo a detailed neurological examination and measurements of rCBF, regional cerebral metabolic rate (rCMRO2), and regional oxygen extraction fraction (rOEF) using PET. Blood pressure will then be lowered pharmacologically in two steps of 7.5 +/- 5 mm Hg each using intravenous labetalol. The neurological examination and CBF measurements will be repeated after each step. This study is not designed to provide data on whether blood pressure in the acute setting improves outcome. This can only be done by randomized treatment trials with clinical outcome measures. These data can, however, be used to help design such a trial and, in the meantime, provide helpful guidelines when reduction in arterial pressure is deemed to be necessary for other reasons. This study will provide esssential information necessary to translate data from animal studies into treatment for human cerebrovascular disease.

高血压是缺血性卒中最重要的危险因素之一。中风后高血压的长期治疗已被证明可将中风复发的发生率降低28%，将主要心血管并发症的发生率降低26%。然而，在急性缺血性中风的情况下，由于人们普遍担心在这种情况下降低血压可能会加剧脑缺血，因此很难确定适当的血压升高治疗方法。这些担忧主要是基于对动物模型中脑血流的研究。药物降压对人类急性缺血性卒中后脑血流的影响的研究很少，也没有提供足够的数据来解决这一问题。本研究项目的目标是确定受控的效果， 应用正电子发射断层扫描(PET)对急性缺血性卒中后rCBF进行分级药物降压，并仔细监测治疗的临床效果和安全性。这一特定的零假设将得到检验：近期脑梗塞和血压升高的患者的平均动脉压(MAP)在药物上降低15+/-5毫米汞柱，并不会在统计上显著减少局部脑血流量。在发病后第3-14天，对60例平均动脉压在120-150 mm Hg的大脑半球脑梗塞患者进行详细的神经学检查，并用正电子发射计算机断层扫描(PET)测量局部脑血流、局部脑代谢速率(RCMRO2)和局部氧摄取分数(Roef)。然后，使用拉贝洛尔静脉注射，分两步用药降低血压，每次7.5+/-5毫米汞柱。每一步后将重复进行神经学检查和脑血流量测量。这项研究的目的不是为了提供急性环境下的血压是否改善预后的数据。这只能通过带有临床结果衡量标准的随机治疗试验来完成。然而，这些数据可以用来帮助设计这样的试验，同时，当出于其他原因认为有必要降低动脉压时，也可以提供有用的指导方针。这项研究将提供必要的信息，将动物研究的数据转化为人类脑血管疾病的治疗。