The University of Michigan Medical School laboratory working to develop an implantable artificial lung that can serve as a bridge to lung transplantation is entering the home stretch.
Thanks to a new $5 million, five year grant from the National Institutes of Health designed to fund animal studies that will move the prototype through the final details of readiness for patients, a small clinical trial of the artificial lung may be just three years away.
“A lot of research has been involved with studying the physiology of the heart and then designing a lung device that uses the heart rather than a mechanical pump – that's what we've accomplished in the last five years. Now we need to refine the device into final form,” says Robert Bartlett, M.D., U-M professor emeritus of surgery. Bartlett, a pioneer in the development of artificial organs, is a principle investigator for the new grant. His laboratory, which has been developing an artificial lung for the last 12 years, has had continuous funding from the NIH since 1971 for the development of artificial organs.
Thirty years ago Dr. Bartlett's laboratory developed a temporary artificial lung system known as ECMO which is used in intensive care units throughout the world to treat patients with acute lung failure, but ECMO is not practical as a bridge to lung transplantation. Currently, there is no mechanical system that can replace lung function well enough and long enough to allow patients months of time while they wait for donor lungs. This device will allow that time.
The implantable artificial lung will not only extend the time to find a donor, but will permit conditioning of the patient.
“People with end-stage lung diseases are often debilitated, and this adds to the difficulty of transplantation and recovery. We know they will do better when they finally get the transplant if they can get into good physical shape before the operation,” Bartlett says. “An implantable artificial lung would permit a patient to be fairly mobile and to live at home, rather than remaining bedridden in an ICU waiting for surgery, as is often the case.”
Another advantage of the implantable lung is that the device can be left in place following transplantation until the transplanted lungs are fully functioning. This will permit accepting lungs for transplantation that would otherwise be declined.
The grant will fund research in collaboration with James Grotberg, Ph.D., and Joseph Bull, Ph.D., at the U-M College of Engineering's Department of Bioengineering. The grant comes from a special bioengineering research partnership category within the NIH. It does not cover clinical trials, but it will fund all the steps necessary to get to that point.
“Because these devices are prototypes, we make them one at a time. An important part of our research from this point forward is to have a device that satisfies the FDA and can be reproduced commercially so that it can be made exactly the same every time,” explains Bartlett.
There also are some remaining physiology experiments that need to take place, Bartlett says. In previous testing, the device has had fairly constant blood flow. Researchers still need to understand the effect of variable blood flow, both higher and lower. When blood flow is lower, clotting can become a factor and the correct use of anticoagulants needs to be defined. When blood flow is higher, the heart has to work harder to pump blood through the device. Exercise requires high blood flow and corresponding demands on the device to provide oxygen. In both cases, small changes will need to be made to the prototype device to make sure it functions under the same varying conditions as the lungs it will replace.
Collaboration on the artificial lung is complex. In previous studies, Grotberg and Bull developed the sophisticated computer technology to simulate the artificial lung in order to predict its performance and fabricate a device to match. The U-M team collaborates with the four other laboratories in the world working on implantable lungs – the Universities of Maryland, Kentucky, Pittsburgh, and Osaka Japan.
Keith Cook, Ph.D., a U-M research investigator and cardiac physiology expert, is the main bioengineer in this, the final phase of the project. Because the prototype relies on the patient's own heart to pump blood through the device, Cook's understanding of how the right ventricle, which does the pumping, works, fails, handles stress, and how the device will perform according to these variables is a complex piece of bioengineering that is vital to the project's success.
Bartlett's team also includes three physicians from the U-M Health System: Jonathan Haft, M.D., an adult cardiac surgeon, Ronald Hirschl, M.D., a pediatric surgeon, and Andrew Chang, M.D., surgical director of lung transplants. The first trial will be conducted with adult patients.
The device itself was fabricated and is being made by Michigan Critical Care Consultants, Inc., or MC3, an Ann Arbor research and development bioengineering firm that Bartlett co-founded 15 years ago with bioengineers Scott Merz, Ph.D., and Patrick Montoya, Ph.D. According to Bartlett, the partnership between the University and MC3 is essential to this project, and is a good example of joint academic/ industrial technology development, currently being encouraged by Steven Forrest, U-M vice president for research.