Potent toxin complicates heart repair.

Each year, heart surgeons in the United States plunge their gloved hands into 350,000 chests to fix faulty plumbing by replacing bad heart valves or bypassing blocked coronary arteries.

Although mortality from the surgery remains low, about 4 percent, complications are common. Yet many of these crises-infections, lung damage, and kidney collapse, among them-seem unrelated to the heart, and doctors have long wondered why they occur.

Now, a study done at Duke University Medical Center in Durham, N.C., indicates that people with low concentrations of an antibody called IgM EndoCAb are more likely to suffer these complications than people with higher amounts of this antibody.

"This is one of the first big studies that suggests that the immune system is important in how people do after surgery," says Elliott Bennett-Guerrero of Mount Sinai Medical Center in New York.

The research, published in the Feb. 26 Journal of the American Medical Association, stitches together an earlier observation that some patients suffer inflammation disproportionate to their surgical trauma and a theory that complications may be caused by a bacterial toxin.

Called endotoxin, the substance is made of pieces of the bacterial cell wall. Although the normal gut safely harbors 25 grams of endotoxin sloughed off by dead bacteria, the substance is so potent that even a tiny leak can cause blood poisoning. Doctors believe that such leaks may occur during surgery, when the gut loses blood, causing tiny holes to appear in the gut wall.

Bennett-Guerrero, formerly of Duke, and his colleagues decided to test whether a person's defenses against endotoxin influence the outcome of surgery. They recruited 301 volunteers scheduled to undergo heart surgery at Duke; 34 of the patients subsequently experienced major complications, and 10 died while in the hospital.

Before surgery, the doctors had removed samples of the patients' blood-which contains antibody-producing white blood cells-to test for total antibody concentrations and for two antibodies to the endotoxins of four species of bacteria: Escherichia coli, Pseudomonas aeruginosa, Klebsiella aerogenes, and Salmonella typhimurium.

The tests showed that just 3.7 percent of the patients with the greatest concentrations of the endotoxin antibody IgM EndoCAb had major complications, compared to 23 percent of those with the lowest amounts. Indeed, this antibody proved a better measure of risk than the amount of the second antibody to endotoxins, total antibody counts, or a profile of 19 standard surgical risks.

"What's so powerful about the study is that we showed IgM EndoCAb is an independent predictor of complications," Bennett-Guerrero says.

"I'm intrigued by this," says Robert G. Johnson of Harvard University. "It's a logical study and a nice step in a new direction."