SCOR-LUNG BIOLOGY AND DISEASES IN INFANTS AND CHILDREN

这份提案来自科罗拉多大学儿科， 寻求5年资金以建立一个新的项目，该项目将调查 新生儿持续性肺动脉高压(PPHN)。PPHN是一种 原因不明的相对常见的(1：500活产)疾病 与高发病率和死亡率(25%-50%)有关，除非接受治疗 几天来，有创性的，昂贵的，有一定风险的体外循环 膜氧合(ECMO)。 我们建议调查最初的侮辱(如氧化剂和 血流动力学应激)和这些侮辱导致 血管反应性改变和血管重塑(增加的基质，和 血管细胞增殖)，PPHN的临床特征。 每年大约有80-100名患者可供研究 已建立的PPHN转诊至丹佛市儿童医院和20 出生在大学医院的高危人群，在那里很早 已经制定了检测程序。对机制的基本见解 在PPHN中手术将来自患者，几个动物模型 新生儿肺动脉高压，以及细胞和分子研究。这个 数据将使早期发现和干预以及更好的治疗成为可能 旨在有效扩张血管和恢复耗尽的抗氧化剂 防御。该计划将提供早期发现，更好的治疗， 最终，预防PPHN。

This proposal from the Department of Pediatrics, University of Colorado, seeks 5 year funding to establish a new program which investigates persistent pulmonary hypertension of the newborn (PPHN). PPHN is a relatively frequent (1:500 live births) disease of unknown origin associated with a high morbidity and mortality (25-50%) unless treated for days with invasive, expensive, and somewhat risky extracorporeal membrane oxygenation (ECMO). We propose to investigate initial insults (such as oxidant and hemodynamic stress) and mechanisms through which these insults lead to altered vasoreactivity and vascular remodeling (increased matrix, and vascular cell proliferation), clinical hallmarks of PPHN. Available for study are approximately 80-100 patients per year with established PPHN referred to The Children's Hospital, Denver, and 20 born to a high risk population at the University Hospital, where early detection procedures have been developed. Basic insights into mechanisms operating in PPHN will be from the patients, several animal models of neonatal pulmonary hypertension, and cellular and molecular studies. The data will allow early detection and interventions and better therapies aimed at effective vasodilation and restoration of depleted antioxidant defenses. The program will provide early detection, better treatment, and ultimately, prevention, of PPHN.