The heart-lung bypass machine that stills the heart while surgeons bypass clogged arteries or repair a cardiac malformation can also trigger a potentially deadly inflammatory response.

An international trial assessed a drug, Pexelizumab, that may block the most deadly of these responses in adults who have coronary bypass surgery.

The study of 5,000 heart bypass patients in about 40 states and three foreign countries is looking at this drug in at-risk patients, including those who have had a previous stroke or heart attack or have diabetes.
Women also are at risk for serious complications, possibly because their smaller size causes their blood to pass through the machine even more times.

As blood moves through the machine where carbon dioxide is removed and oxygen is added, oxygen-carrying red blood cells literally get beat up.
Oxygen-carrying, iron-rich hemoglobin is supposed to be carried by red blood cells. But it can escape from bypass-battered cells, generating oxygen-free radicals that destroy tissue.
Macrophages, scavenger-like cells that roam the body, have a surface receptor called CD 163 which binds the protein haptoglobin. Haptoglobin in turn binds free-floating hemoglobin so the macrophages can eliminate it.

“ One of the theories we have is that in some children, CD 163 may be deficient or not up-regulated as much as it should be,” says St. Louis.

To better understand the action of CD 163 in these children, St. Louis is measuring levels in newborns before, during and after surgery and looking at the expression of macrophages in heart tissue.

He’s also looking at the complement system activated by bypass which in children can cause leaking of endothelial cells that line blood vessels.

“ One of the biggest problems after surgery is the kids swell,” St. Louis says, a result of this leaking than can pull the blood vessel wall lining apart. “ We are trying to figure out why at this point,” he says, noting that children already receive steroids beforehand to up-regulate CD 163 and suppress the immune response.

He believes the ‘why’ may again be an issue of mal-regulation. One of his clinical studies is looking at expression of factors that regulate immunity, such as NFkappaBeta, in hypoxic and non-hypoxic children. He’s also looking at the contributions of NFkappaBeta to cell leakiness that occurs in some children. “ We want to figure out what causes leakiness so we can stop it,” says St. Louis, who says it’s likely a signaling process that goes back to the oxygen-free radicals released by battered red blood cells.

Source: Medical College of Georgia, 2005


XagenaMedicine2005