By Kim Roth

Patient on ventilator, which assists breathing but isn’t a long-term option for those with diseased or damaged lungs.

hronic lung diseases such as pulmonary fibrosis and emphysema afflict more than 13 million Americans and have no cure. For patients to survive, they require transplantation of a living human lung. However, geographic obstacles and a patient’s state of health often impede donor-recipient matches. Those needing a transplant wait an average of two years for a lung; 20 percent die before receiving one.

College of Engineering researchers are currently conducting two programs—the Total Artificial Lung (TAL) and Total Liquid Ventilation (TLV)—that not only might lead to the relief or elimination of many life-threatening respiratory disorders, but also could someday sustain those who require a lung transplant but must wait for an available compatible organ.

The Total Artificial Lung

James Grotberg, professor, Biomedical Engineering and surgery, and medical school colleague Robert Bartlett, M.D., professor, general surgery and chief, Division of Critical Care, are working to develop an artificial lung that will “bridge” more patients to transplantation. By stabilizing patients who have diseased lungs, the device will increase opportunities for donor-recipient matches as well as improve transplant survival rates. Researchers estimate that annual lung transplants would subsequently increase from some 1,500 to several thousand.

The Total Artificial Lung (TAL), manufactured by MC3, Inc., is about the size of a soda can. It could someday sustain those who require a lung transplant but must wait for an available organ.

About the size of a soda can, the device is connected to the heart’s right ventricle. It relies on the heart—not a mechanical pump—to send blood through the lung, where it receives oxygen (and offloads carbon dioxide) as it flows through arrays of microfibers, or membrane oxygenators. Oxygen-rich blood passes from the device into the left atrium and then to the rest of the body.

Funded by a Bioengineering Research Partnership award from the National Institutes of Health, Grotberg and his team of six graduate and post-doctoral students have been building computer models and conducting analyses of the fluid mechanics of blood and the process of gas exchange that occurs when oxygen and carbon dioxide move across the microfiber arrays—all done “with an eye toward suggesting improvements,” he said.

Some of the issues the team is exploring include the optimal shape of fiber arrays (square or triangular, for instance); the optimal distance between fibers; the ideal diameter; and the number of fibers needed within the artificial lung. The challenge is the shortage of existing research to build on. “We have to do it ourselves,” Grotberg said. “A lot of work has been done on flow across arrays of tubes, but those flows are steady with time. The heart (which drives them) pulsates, and there’s been no work done on pulsatile flow.”  

Right now, the team is analyzing pulsatile blood flow over a single microfiber. Next they’ll explore that flow over an array or bundle and validate their computer models with bench-top experiments. “It’s a fundamental problem,” Grotberg said, “one not yet solved in our field.”

Total Liquid Ventilation

If you've seen The Abyss, the 1989 science-fiction film in which a human diver breathes liquid, you’ve seen Total Liquid Ventilation (TLV) in action.

Whereas humans would drown when submerged in water because it can’t provide the proper levels of oxygen, there are “breathable fluids”—in fact, though it’s counter-intuitive, breathing liquids is easier on the lungs than breathing gases. In TLV, a patient’s lungs are completely filled with breathable liquids such as perfluorocarbons (PFCs), which have twice the density of water and the same viscosity, are non-toxic and able to hold high levels of dissolved oxygen and carbon dioxide. The patient is then put on a ventilator, which oxygenates and moves the liquid into and out of the lungs. It’s a regimen that has the potential to improve pulmonary function, reduce acute lung inflammation and injury, and facilitate respiration in those who suffer from respiratory ailments such as pneumonia and Acute Respiratory Distress Syndrome (ARDS).

This image demonstrates how blood flows (right to left) around a single microfiber (circle) such as those used in the Total Artificial Lung. The blood’s velocity determines the volume passing around the microfiber; the strength of the flow varies due to the pulsatile movement. Understanding how these factors affect the overall transport of blood around microfibers is critical to the development of an artificial lung that’s small enough for implantation in a patient.

To understand how TLV works, it’s necessary to know a little about how the lung works.

The inside of the lung is coated with a thin layer of liquid, and where it meets air, there’s surface tension. If the tension gets too high, as it can when there’s severe infection or trauma, the surfactant system doesn’t function properly and the lung gets stiff, making breathing difficult. In TLV, surface tension is reduced by the liquid-to-liquid interface, so lung compliance increases, reducing inflationary pressure and making breathing less laborious. TLV can also aid in removing debris and toxins. 

Funded by an NIH Bioengineering Research Partnership, Grotberg and colleague Ronald Hirschl, M.D., associate professor of surgery, are using mathematical models of gas transport and gas exchange to develop optimal strategies for the use of TLV in patients with ARDS. One key question is: How long should the inspiration phase be? That is, should there be a pause while the lung sits inflated?

“There are an infinite number of possibilities,” Grotberg said. “With quantitative models that accurately reflect the fluid mechanics, you begin to limit them.” So far, early findings indicate that a “breath hold,” or pause, can increase gas exchange by a significant percentage. “That’s not something you might guess, but that’s what the models are helping us determine.”—E

Kim Roth is a freelance writer who has contributed to the Chicago Tribune, the Chronicle of Philanthropy and The Washington Post.