MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD

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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.