[biomed] /. technologyreview: keeping lungs alive outside the body

[Alejandro Dubrovsky]

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Friday, April 17, 2009
Fixing Lungs Outside the Body
A technique may double the number of lungs available for transplant.
By Tim Hornyak

Lung transplant offers hope of a longer life for patients with end-stage
respiratory diseases such as emphysema and cystic fibrosis, with some
surviving for years following surgery. But due to chronic shortages of
viable organs for transplant, only about 25 percent of patients on
waiting lists receive new lungs. However, a new out-of-body lung-repair
technique developed at the Toronto General Hospital may dramatically
increase the number of lungs that can be used in transplants and improve
surgical outcome.

In an operating room at the hospital, the technology can keep a pair of
human lungs slowly breathing inside a glass dome attached to a
ventilator, pump, and filters. The lungs are maintained at normal body
temperature of 37 °C and perfused with a bloodless solution that
contains nutrients, proteins, and oxygen. The organs are kept alive in
the machine, developed with Vitrolife, for up to 12 hours while surgeons
assess function and repair them.

Normally, as few as one in ten lungs available for transplant is usable,
and even those may not work properly when grafted. "The system allows
you to assess the lungs, to diagnose what's wrong with them, and then
repair them," says Shaf Keshavjee, who directs the hospital's Lung
Transplant Program. "Therefore, we're transplanting lungs that have a
more predictable outcome."

The shortage of donor organs is partly the result of outdated
preservation techniques. Organs are conventionally cooled after
harvesting, which inhibits their function and poses risk of injury.
While the Toronto system isn't the first to eschew cooling preservation
for lungs, it improves upon a technique to recondition nonviable lungs
developed at Lund University Hospital, in Sweden. The Toronto system can
maintain the lung outside the body for much longer and poses less risk
of injury, according to the researchers. "We're keeping it in a
protective setting without adding more injury so it can begin to heal,"
says Keshavjee.

An effective lung preservation and repair system would have a major
impact on the lives of thousands of patients in the United States
waiting for donor lungs. Keshavjee says that the number of acceptable
donor lungs can be doubled through the system.

Following years of lung transplant and repair experiments on lungs in
mice, rats, and pigs, last December, Keshavjee's team used the technique
to successfully transplant unacceptable human donor lungs into a
56-year-old man with respiratory illness. Since then, six other patients
have received lungs treated with the technique as part of a clinical
trial. "They've all done superbly, every single one of them," says
Keshavjee. "We're now able to use lungs that we couldn't use before."

Other experts hail the Toronto technique but caution that more work is
needed on how to fix lungs, stop the inflammatory response in grafting,
and improve mortality in transplant patients.

"The Toronto system seems to re-create normal lung function outside the
body," says Jacques-Pierre Fontaine of Brown University's
cardiothoracic-surgery division. "If we can keep the organ outside the
body longer with minimal ischemic damage, we can go farther to get a
lung." However, says Fontaine, "the real test" will be how well the
patients do with the transplanted lungs. "Proof will be in the survival
data."

Joshua Sonnet, director of lung transplant at Columbia University
Medical Center, agrees that the Toronto system is an improvement that
brings existing technology to the next level, where it can act as a
springboard to wider use. "We have two major problems: an organ
shortage--and this [Toronto] system helps with that immediately, if we
can start to recondition some lungs. More importantly, the other problem
is having those organs last a long time. Mostly, they don't last because
of chronic rejection and the side effects of medicines we use to keep
them from getting rejected. So as we're able to manipulate these organs
out of the donor body, we're able to do things and improve them so not
only do they work immediately better and can [they] be transplanted,
but, even more exciting, they work."

Copyright Technology Review 2009.