Pulmonary Venous Obstruction in Congenital Heart Disease

Principal Investigator(s):

  • Chris Caldarone, MD, FRCSC
  • The Hospital for Sick Children
  • Toronto, Canada

Project Abstract:

Statement of Problem:
Pulmonary venous obstruction means that there is blockage of the blood flow from the lungs to the heart due to scar tissue. This is a significant problem in patients with congenital heart disease, and unfortunately is often fatal. Surgery can be used to remove the obstruction when it is localized near the heart, but once established, the obstruction often spreads throughout the pulmonary veins causing life-threatening elevations of the blood pressure in the lungs. Stents are stainless steel tubes that can be inflated with a balloon. Stents are often used as a less invasive alternative to surgery in patients with severe obstruction – but the outcomes are uniformly poor because the changes in the pulmonary veins progress to further obstruction. This scarring process then blocks the stent, and the problem returns.

Objectives of Research:
The objective of this research is to find a treatment that prevents and treats the scarring process that causes pulmonary venous obstruction. We want to find specific drugs or molecules that can work in patients, since no treatments are very effective right now. To accomplish this goal, we need to understand in detail what causes damage to the lining cells in the lung that are affected. We see this as a 3 step process. 1) It is first necessary to understand the detailed changes inside the cells that line the lung vessels that are affected by this process. These cells are called endothelial cells. We recently discovered that these cells become abnormal and start to produce fibrous tissue, or scar. This gives us a big clue since this process was also discovered to occur in other blood vessel diseases like diabetes. 2) We then will do experiments in isolated blood vessel cells from lungs in which we try to prevent and even reverse this scar process using drugs that we think may work. 3) The final step is to try these drugs in the body using a special animal model of lung vein scarring. Together, these experiments will guide us as to how to treat patients more effectively.

Conclusion:
Pulmonary venous obstruction in children is common and poorly understood. Because this disorder occurs mainly in children, it has not received much attention in the lay community or by scientists. Our recent discoveries have given us important clues to what causes this deadly disease. The proposed experiments will allow us to evaluate the mechanisms involved in pulmonary venous obstruction and, hopefully, solve a vexing clinical problem.