POST ISCHEMIC PLATELET FUNCTION--YOUNG VS ADULT

脑缺血是一种严重的，潜在的致命威胁， 患有涉及大脑功能减退的病理过程的患者 灌注。 血小板被认为是引起 与血栓栓塞性血管闭塞相关的脑缺血， 缺血性损伤后神经损伤的调节剂。 但据 脑缺血是否或通过何种机制诱导异常尚不清楚 在血小板的功能，从而创造了一个载体， 再灌注或血管重建期间的损伤。 此外，小 存在关于短暂性缺血对血小板的影响的信息 在新生儿中发挥作用。 因此，本文的总体研究目标 项目是在临床相关模型中检查血小板反应性 并确定新生儿的反应是否 羔羊血小板不同于成熟绵羊。 全球不完整 通过输注人工CS产生缺血15分钟， 同时允许MAP自发地变化并且ICE被调节 相应地 4小时内的基线和连续测量 再灌注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， 将确定脑缺血对血小板反应性的影响， 通过检查血小板表面的变化，比较新生动物与成熟动物 抗原、血小板聚集和颗粒分泌。 血小板变化 再灌注2、30和240分钟时的表面糖蛋白将 使用流式细胞术评价。 离体血小板聚集和 将使用阻抗对全血进行分泌研究 分别在2、30和240 min时进行聚集测定和光度测定。 再灌注 在AIM 3和4中，将研究两种潜在的机制， 缺血诱导的血小板功能障碍。 我们将确定硝酸 或血小板活化因子在血小板活化中起作用， 利用一氧化氮在新生绵羊与成熟绵羊中缺血/再灌注 合成酶（L-NNA）和PAF（BN 52021）抑制剂。 结果 从这项研究将提供生理学原理的护理， 心脏骤停、创伤、中风和脑血管疾病后的患者 损伤 此外，检测到的时间年龄相关的变化后， 缺血性血小板功能将阐明发育差异， 影响护理治疗针对危重新生儿。

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.