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DURHAM, N.C. --- Older patients with lowered immunity to
certain common bacteria found in the gastrointestinal tract are
more likely than younger patients to suffer cognitive decline
after coronary artery bypass surgery, according to a new
analysis by Duke University Medical Center researchers.

The results of the Duke study were published in the February
2003 issue of the journal Stroke.

Within the gut resides a class of bacteria known as
gram-negative bacteria. These bacteria can release endotoxins
into the bloodstream as a result of action of the heart-lung
machine -- which circulates the blood throughout the body while
surgeons operate on a stopped heart -- triggering a cascade of
immunological events including systemic inflammation.

Since the machine does not circulate blood like the heart,
the researchers said, the mucosal lining of the gut undergoes
periods of low perfusion. During these periods, the
gastrointestinal tract becomes more susceptible to bacteria
crossing into the bloodstream.

Physicians can determine a patient's level of immunity to
these bacteria by measuring the number of antibodies (EndoCAB)
in the bloodstream that the body has created in response to the
bacteria.

"In our study, we found that reduced preoperative levels of
EndoCAB are a predictor of postoperative cognitive dysfunction
in patients undergoing bypass surgery," said Joseph Mathew,
M.D., Duke anesthesiologist and principal investigator of the
study. "Among patients who undergo bypass surgery, low
endotoxin immunity may exacerbate the inflammatory response
typically associated with the heart-lung machine and cause
greater cognitive dysfunction.

"This effect was particularly pronounced in patients over
the age of 60," he said.

Each year, more than 750,000 patients worldwide undergo
bypass surgery, and a 2001 Duke study published in the New
England Journal of Medicine found that five years after such
surgery, 42 percent of patients had measurable cognitive
declines. In that study, age was found to be a predictor of
cognitive decline, but the study was not designed to determine
the reasons.

For the current study, the Duke team followed 460 patients,
ranging in age from 23 to 87, scheduled to undergo elective
bypass surgery. The researchers took EndoCAB measurements of
each patient, and gave them a standard battery of cognitive
tests just before surgery and then six weeks after. The tests
measure such cognitive abilities such as short-term memory,
attention, concentration, language comprehension, abstraction
and spatial orientation.

Of all the patients, 36 percent suffered measurable
cognitive decline six weeks after surgery.

"While we looked at many variables, EndoCAB level had a
significant statistical interaction with age, indicating to us
that the protective effect of EndoCAB is different in younger
and older patients," Mathew explained. "Younger people have
more robust immune responses, so they are better able to 'soak
up' the endotoxins released as a result of surgery and negate
their inflammatory effects."

Mathew said that strategies to boost immunity might have the
potential to improve the outcomes of older patients. Therapies
could include drugs that modulate the immune response or
stimulate the production of the EndoCAbs, he said, adding that
Duke will be one site of many involved in a clinical trial
testing the effects of giving antibodies to older patients
before surgery.

Last year, the Duke team reported that patients with lowered
EndoCAB levels were more likely to suffer severe kidney damage
as a result of bypass surgery. The researchers say that
possible strategies used to protect the brain during surgery
may also have a beneficial effect on renal function.

"We need to address the issue of cognitive decline because
we are successfully operating on a progressively older and
sicker group of patients," Mathew said. "While many of the
complications of cardiac surgery have been minimized, cognitive
decline is still one of the main areas that continued research
can improve the quality of life for these patients."

The researchers were supported by the National Institutes of
Health.

Other members of the team, all from Duke, include: Hilary
Grocott, M.D., Barbara Phillips-Bute, Ph.D., Mark
Stafford-Smith, M.D., Daniel Laskowitz, M.D., Daniel Rossignol,
Ph.D., James Blumenthal, Ph.D. and Mark Newman, M.D.