INFLAMMATION IN THE COURSE OF EARLY MYOCARDIAL ISCHEMIA

项目1描述了细胞和分子机制， 介导急性炎症反应和随之而来的组织损伤 犬心肌缺血再灌注的实验研究。它 利用我们不断开发的独特模式 我们可以：1)插入心脏淋巴管，这样我们就有了 在短暂(1-2分钟)延迟的情况下进入心脏细胞外液 这使得能够在缺血期间进行纵向时间采样 再灌流方案。2)通过对多个组织样本进行校准 关于缺血冠脉血流量和再灌注时间，我们可以 组织学、免疫组织化学和分子特征的相互关系和3) 利用以上内容，我们可以开发几种独立的策略来 测量白细胞转运作为持续时间和程度的函数 缺血和再灌流持续时间。实验阐明了 利用时间关系和病理关联 研究细胞因子和抗体诱导的分子和抗体探针 体内外各种细胞群中的黏附分子。在……里面 此外，单抗和细胞或分子特异性 抑制剂被用来评估特定细胞的作用 调解人事件。每个假设都由几个独立的 试验性战略；总体目标与 项目2和项目3中的项目。 这四个具体目标是为了：1)描述趋化性 介导白细胞整合素活化的信号，2)检查 白细胞内流、细胞黏附与细胞因子的关系 在再灌流期间的诱导，3)检测组织和 细胞间黏附分子-1和血管细胞黏附分子-1和4)的细胞生物学比较 冠脉闭塞时间较长后再灌注时的炎症反应 一小时闭塞的机制已阐明。

Project 1 characterizes the cellular and molecular mechanisms which mediate the acute inflammatory response and tissue injury ensuing upon reperfusion of the previously ischemic myocardium in a canine model. It takes advantage of a unique model which we have continually developed in which we are able to: 1) Cannulate the cardiac lymph duct so that we have access to cardiac extracellular fluid with a brief (1-2 minute) lag time which enables longitudinal temporal sampling during the ischemia reperfusion protocol. 2) By calibrating multiple tissue samples with respect to ischemic coronary blood flow and time of reperfusion we can correlate histologic, immunohistochemical, and molecular features and 3) Utilizing the above, we can exploit several independent strategies for measuring leukocyte trafficking as a function of the duration and extent of ischemia and duration of reperfusion. The experiments elucidate temporal relationships and pathological correlations by utilizing molecular and antibody probes to study induction of cytokines and adhesion molecules in various cell populations in vivo and in vitro. In addition, monoclonal antibodies and cell or molecular - specific inhibitors are utilized to evaluate the role of specific cellular mediator events. Each hypothesis is tested by several independent experimental strategies; the overall goals are highly concordant with those in projects 2 and 3. The four specific aims are designed to: 1) Characterize chemotactic signals mediating leukocyte integrin activation, 2) Examine the relationship between leukocyte influx, cell adhesion and cytokine induction during reperfusion, 3) Examine the induction of both tissue and soluble forms of ICAM-1 and VCAM-1 and 4) Compare the cell biology of inflammation during reperfusion after longer occlusion times with the mechanisms elucidated for a one hour occlusion.