Pulmonary Hypertension Program

1. Inhaled oxygen. A lower than normal amount of oxygen in the lungs causes the lung's blood vessels to constrict. Increased oxygen causes dilation of these vessels, although this effect is very small for people who have normal oxygen levels to begin with. Increasing the amount of oxygen in the lungs can be very useful for patients with lung disease or other cause of decreased oxygen in the lungs. Giving oxygen may be particularly beneficial while sleeping, when some people have a tendency to breathe less strongly as when awake. The oxygen is given by two very small tubes in the very front of the nose ("nasal cannula"), and can be administered even when the person is walking about.

The advantages of oxygen therapy are that it can be quite effective in certain patients, and is very safe. Its chief disadvantage is that the patient has to wear the nasal cannula, and carry a source of oxygen. Oxygen is most often prescribed for patients with certain forms of lung disease, or whom are thought to have low oxygen levels while sleeping.

2. Like inhaled oxygen, inhaled nitric oxide (iNO) also relaxes pulmonary blood vessels. It can be given in much the same way as oxygen, although for a variety of reasons has seldom been used in patients outside of the hospital setting. The most common use of iNO is for short-term (usually hours or days) therapy for pulmonary hypertension in hospitalized patients, or for testing the "reactivity" of the pulmonary arteries (i.e., whether they can relax given a vasodilator) during heart catheterization.

3. Certain types of calcium-channel blockers (e.g., nifedipine and diltiazem) can be given by mouth to treat pulmonary hypertension. They relax pulmonary blood vessels by decreasing the flow of calcium into the smooth muscle in the wall of the pulmonary arteries. These were the first drugs used on a wide-scale basis to successfully treat pulmonary hypertension. Unfortunately, the substantial majority of patients (especially adolescents and adults) do not respond to calcium channel blockers (their pulmonary artery pressure changes little or not at all when given the drug), and many who do respond at first lose this responsiveness with time.

Epoprostanol's chief disadvantage is that it needs to be given continuously through an intravenous line. This is because it is broken down very quickly in the body, and lasts only a few minutes in the blood stream. (In fact, it is unstable even outside the body, and needs to be kept cold if not used within about 8 hours of preparation.) Patients have a permanent intravenous line (catheter) surgically placed, and carry with them a very small pump which provides the prostacyclin. It is important that the epoprostanol infusion not be stopped, as a dangerous increase in pulmonary artery pressure can occur if this medication is suddenly discontinued. Patients and their families must be very careful in caring for this catheter, to prevent damage and minimize the risk of infection.

5. Treprostinil ("Remodulin") is another form ("analogue") of prostacyclin. It is broken down much more slowly than epoprostenol, and can be given using a small, self-inserted catheter placed just under the skin ("subcutaneous"). Avoiding the need for an intravenous catheter is an advantage, but for some patients pain at the site of infusion is too much to be tolerated. Treprostinil can also be given by intravenous infusion, and because it is more stable than epoprostenol new medication needs to be prepared less often, and no ice is needed to keep the medication cold.

6. Iloprost ("Ventavis") is yet another analogue of prostacyclin, which is also more stable than epoprostenol. It can be given by inhalation, avoiding the need for an intravenous or subcutaneous catheter, although for optimal effect the drug must be inhaled about 6-9 times / day.

7. Bosentan ("Tracleer") is a member of a class of drugs known as endothelin receptor antagonists. Endothelin-1 is substance normally produced in the body. It causes contraction of smooth muscle in the walls of blood vessels, and growth of smooth muscle and other cells. In at least some patients with pulmonary hypertension a greater than normal amount of endothelin is produced, causing vasoconstriction and remodeling. By sticking to the endothelin "receptor" on the outside of smooth muscle and other cells, it blocks the effect of endothelin-1. Studies have shown this medication can increase exercise capacity and (although to only a small degree) decrease pulmonary artery pressure. Bosentan can be taken orally. Because it sometimes causes liver damage, blood tests of liver function are regularly monitored.

9. Sildenafil ("Rovatio"). This drug is also known as Viagra. It relaxes small pulmonary arteries by increasing a substance called cyclic AMP (cAMP) inside the smooth muscle. Because cAMP causes smooth muscle to relax, increasing this substance tends to reduce constriction of blood vessels. Sildenafil can be given by mouth, and does not require as close monitoring as the endothelin receptor antagonists.

10. Anticoagulants such as warfarin ("coumadin") help prevent blood clots from forming in the lungs (and elsewhere in the body). Anticoagulants probably do not decrease pulmonary hypertension, but may help slow its progression.

11. Lung transplantation may be recommended for patients with severe pulmonary hypertension who do not respond to medication. Because lung transplantation carries the life-long need for very close monitoring, multiple medications, and risk of complications, it is reserved for the relatively small number of patients with severe pulmonary hypertension who do not respond adequately to medicines.

1. The body tends to hold on to excess fluid when the heart's function is reduced. Diuretics (e.g., Lasix) cause the kidneys to eliminate water and help maintain an appropriate fluid balance.

2. Digoxin helps the heart to contract more strongly and is may be used if the heart is weakened.

3. In severe pulmonary hypertension with a very weak right ventricle, it may be helpful to create a small hole between the upper chambers of the heart. This allows some blood to bypass the right ventricle so that it can be pumped to the body by the left ventricle. This procedure is done in the catheterization laboratory.