Xenon Shows Promise in Protecting – The Brain During Bypass Surgery

In studies using rats, researchers from Duke University Medical Center (USA) and 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 are published in the March 2003 edition of the journal Anesthesiology.

“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 one 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. 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.

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 five percent of surgery cases, cognitive decline is much more common, the researchers say.

In studying stroke in animal models, researchers at Imperial College London 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 Medical Division, Joining Grocott in the study from Imperial were Daqing Ma, M.D., Nicholas Franks, Ph.D., and Mervyn Maze, M.B., Ch.B. Other Duke team members were Hong Yang, M.D. and John Lynch, M.D.