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Transatlantic Network on Pulmonary Vascular Remodeling: Early Determinants in Congenital Heart Disease

European Coordinator:
  • John HESS, Deutsches Herzzentrum München an der TU München (Germany)
North American Coordinator:
  • Jeffrey FINEMAN, University of California, San Francisco (USA)
Members:
  • Ian ADATIA, University of Edmonton (Canada)
  • Stephen M. BLACK, Medical College of Georgia (USA)
  • Sohrab FRATZ, Deutsches Herzzentrum München an der TU München (Germany)
  • Agnes GÖRLACH, Deutsches Herzzentrum München an der TU München (Germany)
  • Thomas KIETZMANN, Technische Universität, Kaiserslautern (Germany)
  • Christian SCHREIBER, Deutsches Herzzentrum München an der TU München (Germany)

In infants with congenital heart disease, the blood vessels of the lungs (pulmonary vasculature) are exposed to increased blood flow and pressure, as well as abnormal oxygen levels.  Over time, in a process called remodeling, the blood vessels undergo changes such as increases in smooth muscle and vascular resistance.  The extent of these changes is the principal determinant of treatment options and outcomes in infants with congenital heart disease.

Single ventricular heart disease, although not the most common congenital anomaly, is associated with the poorest outcomes. A normal heart has two ventricles, which allows for pumping of blood under low pressure to the lungs, and under high pressure to the rest of the body. The heart with only a single ventricle can only pump at one pressure, and therefore blood is pumped to the lungs at the same high pressure that it is pumped to the rest of the body. Ultimately it is the effects of high pressure on the lungs which results in the harmful pulmonary vascular remodeling of this congenital condition.  Furthermore, because surgical treatment (total cavopulmonary connection) of infants with single ventricle physiology results in passive blood flow to the lungs without a pumping ventricle, prevention of vascular remodeling and maintenance of the normally low resistance in the pulmonary circulation is especially important in this group of patients.

The overall objective of this Network is to investigate the mechanisms underlying pulmonary vasculature remodeling in congenital heart disease and to apply the findings to optimize surgical and pharmacological options for its prevention and treatment.  The translational approach spans the use of biochemical and molecular techniques, DNA microarray and metabolomic analysis, models of congenital heart disease in fetal and newborn lambs, and human clinical studies.