Every Breath You Take

UK's Jay Zwischenberger Refining Artificial Lung

by Jeff Worley
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We take our next breath for granted. We don’t think about it. We just go about our business, or pleasure, and there it is, regular as the tick of a clock.

But imagine that this gift of breath has been damaged beyond repair. Your only hope is a lung transplant. Your doctor tells you that currently in the United States around 3,500 patients a year wait for a lung transplant, but only 1,000 of them have the operation due to the lack of donors. Unfortunately, the majority of those in need of a transplant will not live longer than one or two years without it. In 2004, more than 500 people waiting for a transplant died. You think about your odds as you wait, listening to time rush by like an icy wind.

The University of Kentucky’s Jay Zwischenberger (his friends and colleagues call him “Zwisch”) is doing something to improve these odds. For the past 20 years, he’s been working with a group of researchers from the universities of Michigan, Pittsburgh and Maryland to develop and refine a miniaturized heart-lung machine that has evolved into an artificial lung apparatus. This device isn’t implanted in place of a donor lung; it’s paracorporeal, or outside of the body, Zwischenberger explains, and small enough to be carried by the patient.

“Our artificial lung is more of a concept than a thing,” he says. “It’s not a single entity but more like a component stereo. With this approach, we can keep refining each component as we learn more about how it’s functioning by itself and in concert with the other devices as technology improves.” He completes the analogy by adding that this approach is clearly superior to an “all-enclosed” system. “You can design an artificial lung like a boom box, where everything’s contained in one unit, or you can design it as a component stereo system. The problem is, you can’t improve upon a boom box—the way it’s put together isn’t changeable.”

Zwischenberger’s system begins with a double-lumen catheter, which has two openings—one for infusion and the other for blood removal—combined with a gas-exchanger with a pump that reduces strain on the heart.

Here’s how it works. His catheter (patented recently with partner Dongfang Wang) transports blood from the
superior and inferior vena cava (veins that carry deoxygenated blood from the upper and lower halves of the body) to a gas exchanger. The gas exchanger removes carbon dioxide and adds oxygen to the blood. The oxygenated blood then returns through the catheter into the right atrium, and the loop begins again.

“Our new double-lumen catheter design directs the venous blood to pass through the artificial lung to allow total gas exchange much more effectively than previous designs,” Zwischenberger explains.

This artificial lung has several advantages over a traditional heart-lung machine: It would allow patients to remain ambulatory, no sedation or breathing tube insertion would be needed, and it would dramatically reduce the possibility of infection. “Our artificial lung would also allow the patient to eat and drink normally, and would reduce the incidence of depression, which often afflicts bed-bound patients,” Zwischenberger adds.

“In developing all three components of this system, we’ve been working with some of the top scientists and
engineers in the world. We’ve collaborated with the best pump-maker to continually improve our pump, and we’ve taken the same approach with our gas-exchange device. We’re working with companies in the U.S. and in Europe to develop all three devices,” says Zwischenberger, who tends to speak rapidly. He’s a man who is eager to tell you the good news.

“There’s work to be done,” he admits, “but we’re well on our way to building an effective bridge to lung transplant.”

In this work, Zwischenberger is using sheep as his animal model. “Their physiology, genetics and size are almost identical to that of a human, and their immunology is very close to ours, too,” he says. “Also, this animal is very easy to work with, especially since all of us on my research team have experience with farm animals.”

Because the wait for a donor lung may be several years, a major focus of Zwischenberger’s project is to keep the sheep alive and healthy much longer than would be possible with a traditional heart-lung machine. “A heart-lung machine is designed to keep a patient going for hours or a few days, possibly for weeks. But not for months,” he explains, his voice dropping with the implications of this sad fact. “That’s our goal—to buy time for patients while they are waiting for a lung donor.”

A Few Decades of Groundwork

Zwischenberger comes to this current research interest from 30 years of work as, first, a cardiothoracic surgeon at the University of Michigan (1977-1986) and then a professor of surgery, medicine and radiology at the University of Texas Medical Branch in Galveston (1986-2007).

“My earliest interest,” he says, rolling back the years, “was in taking care of babies who were dying. In the late ’70s and early ’80s, they died frequently from meconium aspiration and from respiratory distress syndrome. The problem is, the more premature they are, the less they’re capable of tolerating either of these conditions. Back then, infants with these syndromes had a 90 percent chance of dying.”

Working with a team headed by Robert Bartlett, an international leader in the development of cardiopulmonary mechanical support systems, Zwischenberger helped develop a technique to treat these endangered babies. This approach, called Extracorporeal Membrane Oxygenation (ECMO), used a heart-lung machine to infuse blood oxygen from outside the body. This way, the blood is given oxygen just as it would be if the lungs or heart were normal.

“We saw a huge and wonderful turnaround then—90 percent of those endangered babies lived,” he says, adding that now the use of ECMO is commonplace. He then used this technique for children with heart failure and found they could be effectively treated as well.

Later, at the University of Texas Medical Branch, Zwischenberger used the heart-lung machine at bedside to aid people for one to three weeks who were suffering from respiratory failure. He also became more and more active in the relatively new field of lung transplantation. It was only after the invention of the heart-lung machine, coupled with the development of immunosuppressive drugs such as cyclosporine, that organs such as the lungs could be transplanted with a reasonable chance of a patient recovering.

“As lung transplants became more and more accepted, it became crucial to have a technique by which you could hold a patient over until he could receive a transplant,” says Zwischenberger. “For a period of time back then, we were losing 20 to 30 percent of our patients waiting for transplant.” So the seeds of his artificial lung were sown.

Back Home in Kentucky

It’s atypical for a faculty member, a university researcher and physician in the later stages of his career to leave an institution where he’s been successful and well-liked for 20 years, but that’s exactly what Zwischenberger did. After two decades at the University of Texas Medical Branch, he packed up his life and came here.

“I was impressed with the direction Jay Perman and Mike Karpf have taken the med center here in the past few years,” he says. “The disciplines here are integrated, and there’s a lot of cross-fertilization among departments.” Perman is dean of the College of Medicine; Karpf is the executive vice president for health affairs. “I also liked that they encourage department chairs to be active. I knew I’d be able to do clinical practice as well as research. It was a perfect fit.

“Also,” he says smiling, “there may have been the magnet effect. My medical degree is from UK, you know.”

And there may have been an even stronger attraction in being drawn back to his alma mater. Zwischenberger was born and raised in Louisville. His father was a seed broker and often took his son along with him on his rounds of the state. “I got to know Kentucky really well this way,” Zwischenberger says, adding that there is also a “family factor” at play in his return to UK. “I have three siblings, and all four of us are UK alums.”

Then, putting long-established UK connections aside, he returns to the present moment and his research. “Looking down the road, I think UK is particularly well positioned to be a leader in the field of artificial lung development. I’ve brought an entire research team with me from Texas, and our College of Medicine has recently renovated the large-animal lab. It’s a terrific facility. And our group has buddied up in this work with basic scientists here who were already standouts in related disciplines.”

Riffing on Better Health

Lung power. This is the focus of Jay Zwischenberger’s work—and play. He just may be the only surgeon in the United States who is never without his harmonica.

“I have it with me at all times,” he says from his medical center office. He slides a harmonica from his lab-coat pocket and blows a few notes. “Would you like to hear western? Blues?”

Zwischenberger is known for playing a tune while he walks through the suite of operating rooms or for patients, who have said that they find “Dr. Z’s” music a source of comfort and reassurance.

Physicians have long believed in the healing power of music, and numerous recent studies have shown music’s power to soothe and help mend the troubled mind and body. A recent study in the Journal of
Advanced Nursing
concluded that people diagnosed with depression who listened to music for at least one hour each day reported a reduction of symptoms by up to 25 percent. When a harpist plays in a neonatal ward in Savannah, Georgia, where premature babies are cared for, the heart-rate monitors on the babies calm down, according to a recent article in the Savannah Morning News.

There’s a growing movement in some U.S. hospitals to introduce music in health care in an innovative
way, and UK is in the vanguard of this new focus, with a program to integrate the arts at the new Albert B. Chandler Hospital. The $450 million facility, scheduled for completion in 2011, will feature a specially designed auditorium adjacent to the building’s main lobby. That may not seem unusual. Teaching hospitals do, after all, need space to conduct classes, as well as to host faculty and guest lectures. But this auditorium will be different. The 300-seat theater will be equipped with state-of-the-art acoustics and audio/visual technology so that musical, dramatic and other live performances can be seen by UK staff, visitors and the public. And for patients who want to come but can’t make it? The performances will be piped directly into their rooms.

“We want to use music and art to make the hospital a more friendly, less daunting place,” says Zwischenberger.

“I’m not aware of another facility that can actually stage live concerts and televise them as the performances are going on,” says Michael Karpf, the university’s executive vice president for health affairs. “This initiative
raises health care to a new level.”

“We have a major grant from the Lucille Little Foundation that will set up a concert series,” Zwischenberger says, “which will include everything from classical music to bluegrass.” The UK School of Music will supply much of the talent from more than 40 ensembles, covering music genres that range from classical to jazz.

“Studies continue to show that music not only has a soothing effect but may also lower blood pressure and heart rate, and stimulate a person’s immune system to ameliorate some diseases,” Zwischenberger adds. “To me, music is both a universal language to allow immediate connection between patients and colleagues, and a discipline, like research, that opens new pathways in your mind.”

photo of catheter

Invented and developed by Jay Zwischenberger and Dongfang Wang, this double-lumen catheter will help patients too sick to be maintained on a ventilator get oxygen into their blood and carbon dioxide out. The FDA approved use of the device last October.

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illustration of artificial lung system

Zwischenberger’s artificial lung design begins with a double-lumen catheter (a), which is inserted into the body through the jugular, the large vein in the neck. The catheter is threaded through the right atrium of the heart, where it sucks de-oxygenated blood out of the upper (superior vena cava) and lower (inferior vena cava) body. The blood is sent through a gas-exchanger (b), which can be tucked into a backpack. This machine removes carbon dioxide and adds oxygen back to the blood before returning it directly to the heart. A tiny membrane inside the catheter separates the oxygenated blood from the de-oxygenated blood. This system is run by a state-of-the-art pump (c). A console device (d) controls the system and can be worn on the belt for access by caregivers.

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photo of Jay Zwischenberger

“There are peer-reviewed studies that focus on the healthful effects of music,” says Jay Zwischenberger. “I started playing harmonica seven years ago. It’s a wonderfully versatile instrument, and I love playing for my staff and patients.”

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artist's rendering of new auditorium

UK is in the vanguard of a new focus to integrate the arts with health care. The new $450 million Albert B. Chandler Hospital will feature a 300-seat theater equipped with state-of-the-art acoustics and audio/visual technology so that musical, dramatic and other live performances can be seen by UK staff, visitors and the public.

Enlarge Photo