MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD

描述(由申请人提供)：首席调查员将开发 在运动测试和儿童培训方面的专业知识，并获得 启动独立研究项目所需的经验和技能 在颁奖期间。首席调查员的长期职业目标 作为一名学院派的儿科心脏病专家将成为一名临床研究员 重点研究运动生理学和心脏康复。 运动不耐受是儿童中一种被忽视的慢性发病率 心脏病。运动能力差会导致自尊心低和生活质量差 生活质量。Fontan手术后的儿童单脑室 而原位心脏移植(OHT)后的儿童也属于儿童 运动能力最低。运动不耐受是否在这些 儿童是由于心肺功能障碍或患有 体力活动减少仍不清楚。骨骼肌和肌肉的作用 决定运动能力的体液反应和运动的效果 对患有心脏病的儿童进行训练是未知的。他们提出了一个 比较体力活动的前瞻性、随机性和对照研究 健康儿童和Fontan或OHT儿童的水平，以评估 骨骼肌、儿茶酚胺和细胞因子与运动能力的关系， 并确定运动训练对心肺功能的影响， 骨骼肌与生活质量。为了进行这项研究， 6至13岁的青春期前儿童，包括40名青春期后儿童 Fontan、40名OHT后儿童和40名健康儿童将被招募。 受试者将随机参加为期六周的耐力训练计划或 计算机车间(不提供培训)。该项目将在五年内进行。 将在夏季举行为期三年的培训课程。以下是测试 将在运动训练完成之前和之后立即进行： 双能X线骨密度仪(DEXA)扫描瘦体重，大腿肌 磁共振成像(MRI)、超声心动图、肺功能 心肺运动试验、儿茶酚胺和细胞因子肿瘤坏死 静息和运动时的肿瘤坏死因子α、白介素1β和白介素6水平； 活动监测员的体力活动水平和生活质量由 问卷调查。他们将把这些测量结果与儿童和 训练与未训练儿童的运动效果比较 对Fontan、OHT儿童和健康儿童进行培训。这项研究是 旨在确定儿童运动不耐受的重要机制 患有严重的心脏病。运动训练的结果将会 提供与以下物质的生理和心理社会益处相关的证据 增加体力活动，为未来的研究奠定基础 心脏病儿童的心肺康复。校长 调查员将参加高级课程，以提高所需的知识和技能 以患者为导向的研究，并与导师合作进行 获奖期间提出的项目。

DESCRIPTION (provided by applicant): The principal investigator will develop expertise in exercise testing and training of children and obtain the experience and skill necessary to initiate independent research projects during the award period. The principal investigator's long-term career goal as an academic pediatric cardiologist is to become a clinical investigator with a research focus in exercise physiology and cardiac rehabilitation. Exercise intolerance is an under-recognized chronic morbidity in children with heart disease. Poor exercise capacity leads to low self-esteem and poor quality of life. Children with single ventricle after the Fontan operation and children after orthotopic heart transplantation (OHT) are among children with the lowest exercise capacity. Whether exercise intolerance in these children is due to cardiopulmonary dysfunction or deconditioning from decreased physical activity remains unclear. The role of skeletal muscle and humoral responses in determining exercise capacity and the effect of exercise training in children with heart disease are unknown. They propose a prospective, randomized and controlled study to compare physical activity level of healthy children and children with Fontan or OHT, to evaluate the skeletal muscle, catecholamine and cytokines in relation to exercise capacity, and to determine the effect of exercise training on cardiopulmonary function, skeletal muscle and quality of life. In order to conduct this study, prepubertal children six to 13 years of age, including 40 children after Fontan, 40 children after OHT, and 40 healthy children will be recruited. Subjects will be randomized to a six-week endurance training program or computer workshops (no training). The project will be conducted over five years and training sessions will be held in the summer. The following tests will be performed before and immediately after exercise training is completed: lean body mass by dual energy X-ray absorptiometry (DEXA) scan, thigh muscle volume by magnetic resonance imaging (MRI), echocardiogram, pulmonary function test, cardiopulmonary exercise test, catecholamine and cytokine tumor necrosis factor (TNF)-alpha, IL-1beta, and IL-6 levels at rest and during exercise, physical activity level by activity monitor and quality of life measures by a questionnaire. They will compare these measurements between children with training and children without training and compare the effect of exercise training on children with Fontan, OHT and healthy children. The study is designed to define important mechanisms of exercise intolerance among children with severe forms of heart disease. The results of exercise training will provide evidence related to the physiologic and psychosocial benefits of increased physical activity and form the basis for future research on cardiopulmonary rehabilitation for children with heart disease. The principal investigator will take advanced courses to enhance knowledge and skills needed for patient-oriented research and work with the mentors to conduct the proposed project during the award period.