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MassGeneral Hospital for Children
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The long-term goals of my laboratory are to explore the fundamental mechanisms of newborn lung injury and to develop novel therapies for pulmonary vascular disease.Lung injury in children often causes abnormal pulmonary arterial vasoreactivity and muscularization. Through processes that are incompletely understood, many children with lung injury develop progressive and irreversible pulmonary hypertension, intra- and extra-pulmonary shunting of deoxygenated blood, and severe hypoxemia.In early studies, we observed that low levels of inhaled NO rapidly cause pulmonary vasodilatation. Furthermore, the dilator effect of inhaled NO was limited to the lungs since it did not cause systemic vasodilatation. After evaluating the dose-response to inhaled NO in the laboratory and developing a safe NO delivery system, we performed the first clinical trials of inhaled NO in pediatric patients with pulmonary hypertension. Low levels of inhaled NO were observed to safely decrease hypoxemia and pulmonary hypertension in critically ill newborns with pulmonary vascular disease and intrapulmonary shunt. Subsequently, my laboratory led a prospective, randomized, placebo controlled, multicenter study that demonstrated that inhaled NO treatment decreases hypoxemia and the requirement for extracorporeal membrane oxygenation (ECMO) in newborns with pulmonary hypertension. These studies stimulated investigations of inhaled NO in the pediatric lung through out the world and were pivotal in the acceptance of inhaled NO by the Federal Drug Administration of the United States as a therapy for pulmonary hypertension and hypoxemia in newborns.
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