Gender Differences in Cardiac Arrest/CPR

心脏骤停/心肺复苏中的性别差异

• 批准号: 6666678
• 负责人: RICHARD J TRAYSTMAN
• 金额: $ 38.95万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6666678
• 关键词: BCL2 gene /protein; RNase protection assay; artificial respiration; behavior test; cardiopulmonary resuscitation; cellular pathology; cerebral cortex; cerebral ischemia /hypoxia; estradiol; estrogen receptors; estrogens; gender difference; gene targeting; genetic transcription; genetically modified animals; heart arrest; heart disorder chemotherapy; hippocampus; hormone therapy; laboratory mouse; neuroprotectants; nonhuman therapy evaluation; outcomes research; ovariectomy; receptor expression; reperfusion

DESCRIPTION (provided by applicant): Despite four decades of research concerning cardiac arrest/CPR, clinical outcome remains poor. Only about 5% of individuals who suffer cardiac arrest are successfully resuscitated to the extent that they are returned to productive lives, and neurologic and neuropsychologic deficiencies remain prevalent in the remaining 95% of patients. Women are at lower risk than men for cardiovascular disease, including stroke (focal cerebral ischemia), yet cerebral ischemic events do occur in both sexes at all ages. Although women have less sudden cardiac death than men, survival differences and neurologic and neuropsychologic evaluations between men and women after cardiac arrest have not been closely examined. The vasoactive hormone, estrogen, has historically been considered to be protective in coronary heart disease, but it is not clear if the steroid is also an important neuroprotectant in either women or men. More critically, the comparative vulnerability of females and males to brain tissue injury once cardiac arrest/CPR is ongoing remains unknown. Our preliminary findings suggest that brains of females are better protected from cardiac arrest/CPR than males, and that estrogen may be involved with this neuroprotection. While protection conferred by estrogen is biologically feasible, specific neuroprotective mechanisms are unknown. The goal of this project is to determine if there are inherent sex-linked neural injury mechanisms in experimental cardiac arrest/CPR, and if 17a-estradiol, the principal biologically active estrogen in mammals, plays a key role in salvaging brain tissue after cardiac arrest/CPR. In Aim 1, we will determine if histopathological and neurobehavioral outcomes after cardiac arrest/CPR are more favorable in female vs male mice, and if exogenous estrogen is the source of neuroprotection. In Aim 2, we will determine if neural injury from cardiac arrest/CPR is exacerbated in transgenic mice deficient in estrogen receptors (estrogen receptor knockouts). Finally, we will examine a neuronal mechanism, hypothesizing that estrogen reduces tissue injury from cardiac arrest/CPR by a Bcl-2 mediated mechanism which is dependent on nuclear estrogen receptors. The proposed study will contribute to our understanding of neurological injury resulting from cardiac arrest/CPR in females and the role of estrogen as a potential neuroprotective therapy for patients of either sex.

描述（由申请人提供）：尽管四十年来关于心脏骤停/心肺复苏术的研究，临床结果仍然很差。只有约5%的心脏骤停患者成功复苏，恢复了正常生活，其余95%的患者仍然普遍存在神经和神经心理缺陷。女性患心血管疾病(包括中风（局灶性脑缺血）的风险低于男性，但在所有年龄的男女中确实会发生脑缺血事件。尽管女性的心源性猝死比男性少，但心脏骤停后男性和女性的生存差异以及神经和神经心理学评估尚未得到仔细研究。血管活性激素雌激素历来被认为对冠心病有保护作用，但目前尚不清楚这种类固醇对女性或男性是否也是一种重要的神经保护剂。更关键的是，女性和男性在心脏骤停/心肺复苏术后对脑组织损伤的相对脆弱性尚不清楚。我们的初步研究结果表明，女性的大脑比男性更容易受到心脏骤停/心肺复苏术的保护，雌激素可能与这种神经保护有关。虽然雌激素的保护作用在生物学上是可行的，但具体的神经保护机制尚不清楚。本项目的目的是确定实验性心脏骤停/心肺复苏术中是否存在固有的与性别相关的神经损伤机制，以及哺乳动物主要的生物活性雌激素17a-雌二醇是否在心脏骤停/心肺复苏术后挽救脑组织中发挥关键作用。在目的1中，我们将确定雌性小鼠比雄性小鼠在心脏骤停/心肺复苏术后的组织病理学和神经行为结果是否更有利，以及外源性雌激素是否是神经保护的来源。在Aim 2中，我们将确定在缺乏雌激素受体（雌激素受体敲除）的转基因小鼠中，心脏骤停/心肺复苏术引起的神经损伤是否会加剧。最后，我们将研究一个神经元机制，假设雌激素通过Bcl-2介导的机制减少心脏骤停/心肺复苏术的组织损伤，该机制依赖于核雌激素受体。这项拟议的研究将有助于我们了解女性心脏骤停/心肺复苏术引起的神经损伤，以及雌激素作为一种潜在的神经保护疗法对男女患者的作用。