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DURHAM, N.C. -- In studies using rats, researchers from Duke
University Medical Center and the Imperial College, London,
have found evidence that the chemically inert gas xenon can
protect the brain from the neurological damage often associated
with the use of the heart-lung machine during coronary artery
bypass surgery.

The researchers say that xenon appears to block receptors on
nerve cells in the brain that can be "overstimulated" in
response to the surgery. This overstimulation can lead to nerve
cell damage or death.

Given the study's results and that xenon has been used
safely in humans for more than 50 years as an anesthetic agent
and for contrast enhancement in computer tomography (CT) scans,
the researchers have begun trials in humans of xenon as a
neuroprotectant in the United Kingdom and plan to extend these
to the U.S. later this year.

The results of the study were published in the March 2003
edition of the journal Anesthesiology and were published
on-line Feb. 26.

"If the clinical trials demonstrate that xenon can have an
impact on cognitive decline after bypass surgery, that could
have a profound impact on the quality of life of these patients
and save health care costs over the long-term," said lead
researcher Hilary Grocott, M.D., Duke anesthesiologist.

"Worldwide, there are more than 1 million heart operations
and previous Duke studies have shown that up to five years
after surgery, 40 percent of these patients suffer measurable
cognitive decline," Grocott continued. "There is a great need
for an effective neuroprotectant to be used in conjunction with
bypass surgery."

There are currently no neuroprotective agents approved by
the Food and Drug Administration (FDA) for use during
surgery.

Xenon is extracted from the atmosphere, and as it is found
only in minute quantities, it is quite expensive. The
researchers said that xenon comprises approximately 0.00009
percent of the atmosphere, and that the only way new xenon can
be produced is by the extreme energy generated by an exploding
star known as a supernova. It is the same element used in the
headlights of cars.

However, the researchers said, newly developed technology
allows researchers to prevent the loss of xenon to the
atmosphere when it is administered during surgery and to
recycle it back to the recipient.

Injury to the brain after surgery -- ranging from subtle
changes in cognition to outright stroke -- remains an important
factor in the quality of life for heart patients after surgery.
While stroke occurs in less than 5 percent of surgery cases,
cognitive decline is much more common, the researchers say.

In studying stroke in animal models, researchers at Imperial
College led by Mervyn Maze, M.B., Ch.B. had shown that xenon is
a potent inhibitor of glutamatergic N-methyl-D-aspartate (NMDA)
receptors on nerve cells. Physiologic insults -- such as stroke
-- can stimulate these NMDA receptors, which researchers say is
crucial in initiating nerve cell damage or death.

With this insight into xenon's capabilities, the research
team hypothesized that it could also protect brain cells from
the effects of the heart-lung machine during bypass surgery.
The machine takes over pumping oxygenated blood throughout the
body while the heart is stopped during surgery. It has long
been suspected that the unphysiologic manner in which it pumps
blood disrupts nerve cells in the brain, leading to the
cognitive decline.

In their studies, the Duke researchers developed a rat model
of bypass surgery and compared rats that received xenon in the
anesthetic gas mixture to those that received anesthetics
without xenon. As part of their study, the rats were required
to perform a series of well-established behavioral tests to
measure their cognitive abilities at different points after
surgery.

"After the first and third days post-surgery, the xenon
group had significantly better neurologic functioning," Grocott
said. "By the twelfth day, the neurocognitive outcome remained
significantly better in the xenon group compared to the group
that didn't receive xenon.

"While we were fairly confident that xenon would have a
protective neurologic effect, we were quite surprised at how
well this effect persisted with time," Grocott said. "These
results give us optimism that xenon may work in humans as
well."

The research was funded by grants from Medical Research
Council, London, and Protexeon Ltd., London, a spin-out company
from Imperial College, London. Xenon was provided by Air
Products and Chemicals, Medical Division.

Joining Grocott in the study from Imperial College were
Daqing Ma, M.D., and Nicholas Franks, Ph.D. Other Duke team
members were Hong Yang, M.D., and John Lynch, M.D.

Contact in UK:

Tony Stephenson, Imperial College and Protexeon
+44 (0) 207-594-6712
+44 (0) 775-373-9766
at.stephenson@imperial.ac.uk