Endothelial progenitor cells and surgical outcomes

描述(申请人提供)：随着人口继续老龄化，接受手术的老年患者数量将急剧上升。他们中的许多人将从手术中获得质量和生命长度的好处。其他人将经历并发症，使他们面临更高的出院风险，这一结果与死亡风险增加相关。更好地了解影响手术结果的因素很重要，原因有两个。首先，它可以通过识别手术风险可能超过好处的患者来帮助指导选择手术的候选人。其次，改进的风险预测可以确定哪些患者可能需要采取旨在改善结果的干预措施。内皮祖细胞(EPC)是成体干细胞的一个亚型，通过其生成内皮细胞和使缺血组织新生血管的能力，似乎可以预防心脑血管动脉硬化性疾病。这两种作用在接受手术的患者中可能具有重要意义，因为手术引起的心脏缺血是心肌梗死的诱因。我们的研究将通过确定EPC是否与术后心肌梗死的风险相关来扩展先前关于EPC在心血管疾病中的作用的观察。我们建议对在加州大学旧金山分校医学中心接受血管手术的125名患者进行为期2年的前瞻性试验，在该试验中，我们将收集术前和术后内皮祖细胞计数和功能的数据，使用临床客观指标(如心电图和肌钙蛋白-L)来确定心脏事件的发生率，并在1个月和6个月时通过电话随访检测其他出院后事件。我们的研究结果将使我们更好地了解大型非心脏手术后恢复的病理生理学，了解如何使用EPC-以及传统的风险指数-来辅助风险分层，并指导未来使用EPC作为治疗方式的预防策略的观察和临床试验的发展。

DESCRIPTION (provided by applicant): As the population continues to age, the number of elderly patients who are candidates for surgery will rise dramatically. Many of them will derive quality and length of life benefits from their surgery. Others will experience complications, placing them at higher risk for discharge to a nursing home, an outcome associated with an increased risk for death. Better understanding of factors influencing outcomes following surgery is important for two reasons. First, it can help guide candidacy for elective surgery by identifying patients in whom the risks of surgery likely exceeds the benefits. Second, improved risk predictions can identify patients in whom interventions designed to improve outcomes may be indicated. Endothelial progenitor cells (EPCs) are a subtype of adult stem cell that appear to protect against cardiac and cerebrovascular arteriosclerotic disease through their ability to generate endothelium and neovascularize ischemic tissues. These two actions are likely to have importance in patients undergoing surgery in that cardiac ischemia induced by surgery is a precipitant of myocardial infarction. Our study will extend previous observations regarding EPC's role in cardiovascular disease by determining whether EPC's are associated with risk for postoperative myocardial infarction. We propose a 2 year prospective trial of 125 patients undergoing vascular surgery at UCSF Medical Center, in whom we will collect pre-and postoperative data regarding EPC count and function, determine the incidence of cardiac events using clinically objective measures (e.g. ECG and Troponin-l), as well as detecting additional post-discharge events through phone follow-up at 1 and 6 months. Our study's results will give a greater knowledge of the pathophysiology of recovery following major noncardiac surgery, yield understanding of how EPC's may be used - along with traditional risk indices - to aid risk stratification, as well as guide the development of future observational and clinical trials of preventative strategies using EPCs as a therapeutic modality.