POST ISCHEMIC PLATELET FUNCTION--YOUNG VS ADULT

脑缺血构成了严重的、潜在的致命威胁 病理过程涉及脑萎缩的患者 灌流。血小板已被认为是一种 血栓栓塞性血管闭塞和AS相关的脑缺血 缺血性损伤后神经损伤的调节剂。然而，它是 尚不清楚脑缺血是否或通过何种机制引起异常。 在血小板功能方面，从而创造了二次大脑的交通工具 再灌注或血运重建过程中的损伤。更远一点，几乎没有 关于短暂性脑缺血对血小板的影响的信息已经存在 在新生儿中发挥作用。因此，这项研究的总体目标是 该项目是在一个临床相关的模型中检查血小板的反应性 并确定新生儿对颅内高压的反应 羔羊的血小板与成熟绵羊的不同。全球不完整 人工CS输注造成脑缺血15分钟， 当地图被允许自发变化和ICE调整时 相应地。在4小时内进行基线和系列测量 再灌流将允许评估脑血流量、脑氧含量 消耗、血小板活化、聚集和分泌。在AIM 2中，我们 将确定脑缺血对血小板反应性的影响 通过检测血小板表面的变化，将新生动物与成熟动物进行比较 抗原、血小板聚集和颗粒分泌。血小板的变化 2、30和240min时的表面糖蛋白。再灌流的时间将是 用流式细胞仪进行检测。体外血小板聚集和 将使用阻抗对全血进行分泌研究 聚集计量法和发光计量法分别在2，30和240分钟。 再灌流。在AIM 3和4中，将研究两种可能的机制 缺血引起的血小板功能障碍。我们将确定硝酸是否 或血小板激活因子在血小板活化过程中起作用 一氧化氮对新生绵羊和成年绵羊缺血/再灌流的影响 合酶(L-NNA)和PAF(BN 52021)抑制剂。发现 本研究将为老年人的护理提供生理学依据 心脏骤停、创伤、中风和脑血管疾病患者 受伤。此外，对后年龄相关变化的检测- 缺血的血小板功能将阐明发育差异， 针对危重新生儿的冲击护理疗法。

Cerebral ischemia constitutes a serious, potentially fatal threat to patients with pathological processes involving diminished cerebral perfusion. Platelet have been implicated both as etiologic agents in cerebral ischemia associated with thromboembolic vessel occlusion and as modulators of neural injury following an ischemic insult. However, it is unknown if, or by what mechanism, cerebral ischemia induces abnormalities in platelet function, thereby creating a vehicle for secondary brain injury during reperfusion or revascularization. Further, little information exists regarding the effects of transient ischemia on platelet function in the newborn. Therefore, the overall research goal of this project is to examine platelet reactivity in a clinically relevant model of intracranial hypertension and to determine if the response of neonatal lamb platelet differs from that of mature sheep. Global incomplete ischemia will be produced for 15 minutes by infusion of artificial CS, while the MAP is allowed to vary spontaneously and ICE adjusted accordingly. Baseline and serial measurements during 4 hours of reperfusion will permit evaluation of cerebral blood flow, cerebral oxygen consumption, platelet activation, aggregation and secretion. In AIM 2 we will determine the effects of cerebral ischemia on platelet reactivity in neonatal vs. mature animals by examining changes in platelet surface antigens, platelet aggregation and granule secretion. Changes in platelet surface glycoproteins at 2, 30 and 240 min. of reperfusion will be evaluated using flow cytometry. Ex vivo platelet aggregation and secretion studies will be performed on whole blood using impedance aggregometry and luminometry, respectively, at 2, 30 and 240 min. reperfusion. In AIM 3 and 4 will examine two potential mechanisms for ischemia-induced platelet dysfunction. We will determine if nitric acid or platelet-activating factor plays a role in platelet activation during ischemia/reperfusion in neonatal vs. mature sheep using nitric oxide synthase (L-NNA) and PAF (BN 52021) inhibitors, respectively. Findings from this study will provide physiologic rationale for nursing care of patients following cardiac arrest, trauma, stroke and cerebrovascular injury. Further, detections of chronologic age-related variation in post- ischemic platelet function will elucidate developmental differences which impact nursing therapeutics directed toward critically ill neonates.