Project 172491

Pulmonary hypertension (high blood pressure in the lung) is a complication that requires medical treatment in about 1 in 500 newborn infants and commonly leads to death in the most severe cases. This disease is common in the newborn period because of two factors: 1) a failure of the normal dilation of blood vessels in the lung at birth that allows oxygen to enter the blood, and 2) rapid development of thickening of the walls of blood vessels (known as remodeling), which blocks the normal passage of blood through the lung and prevents vessels from properly relaxing. The treatments we currently have available to treat babies with pulmonary hypertension often do not work, do not improve remodeling of blood vessels and have not been shown to decrease death or to improve outcome in the long term. The overall goal of my research is to develop more effective treatments for the prevention and treatment of pulmonary hypertension in newborns. To facilitate this goal, my laboratory has developed two newborn rat models of chronic pulmonary hypertension, which have many similarities to human newborns that do not respond to conventional treatments. Published and preliminary work from my laboratory indicates that the induction of high carbon dioxide levels in the blood (hypercapnia) can prevent lung injury and improve pulmonary hypertension in newborn rats. The aims of our proposed work are to further define the "dose" of hypercapnia that is required to effectively treat pulmonary hypertension, to better understand how hypercapnia works, to ascertain its effects on lung development and to see whether its beneficial effects will last into adult life. This work will provide new insights with a high potential for clinical translation. Hypercapnia has great potential as an effective and enticingly simple therapeutic approach to an otherwise intractable problem.