AUTOREGULATION OF CEREBRAL BLOOD FLOW IN ACUTE ISCHEMIA

高血压是缺血性脑卒中最重要的危险因素之一。卒中后高血压的长期治疗已被证明可将卒中复发率降低28%，将主要心血管并发症降低26%。然而，在急性缺血性卒中的情况下，由于在这种情况下降低血压可能会加重脑缺血，因此很难确定血压升高的适当治疗方法。这些担忧主要基于动物模型中CBF的研究。关于药物降低人类急性缺血性卒中后血压升高对CBF影响的研究很少，并且没有提供足够的数据来解决这个问题。本研究项目的目标是确定控制， 采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。将检验这一特定的零假设：在近期脑梗死和血压升高的患者中，平均动脉压（MAP）药理学降低15 +/- 5 mm Hg不会导致局部脑血流量的统计学显著性降低。将实施该特定目标：在发病后第3-14天，60例半球脑梗死和平均动脉血压为120-150 mm Hg的患者将接受详细的神经系统检查，并使用PET测量rCBF、局部脑代谢率（rCMRO 2）和局部氧摄取分数（rOEF）。然后使用静脉注射拉贝洛尔分两步降低血压，每步7.5 +/- 5 mm Hg。在每个步骤后，将重复进行神经系统检查和CBF测量。这项研究的目的不是提供关于急性环境中血压是否改善结局的数据。这只能通过具有临床结局指标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，当由于其他原因而认为有必要降低动脉压时，可以提供有用的指导。本研究将提供必要的信息，从动物研究的数据转化为治疗人类脑血管疾病。

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.