Christopher Reeve is a determined man. The actor, known for playing Superman in the movies, actually may be showing even greater strength of character than the superhero through his perseverance—and good spirits—in light of eight years of paralysis from a horseback riding accident.

His determination led him to volunteer to have implanted an experimental breathing system that is being tested at University Hospitals of Cleveland and Case Western Reserve University. The system consists of implanted electrodes and wires and a small external battery pack. It electrically stimulates two nerves, called the phrenic nerves, in his diaphragm muscle to help him breath more naturally. Severe spinal cord injuries block the brain signals that normally stimulate these nerves. When this happens, people who are paralyzed must rely on mechanical ventilators, which are bulky, conspicuous and noisy.

Reeve is only the third patient to have received the new device, and it will take months before researchers know for sure whether it will work as hoped. (Although the device continues to work well for the first volunteer, who received it three years ago, it did not work for the second volunteer.) While Reeve currently can use the device for only 15-minute intervals, two weeks after his surgery, signs look positive. His volunteer efforts, with the efforts of the other volunteers, will help researchers make continuous improvements that may benefit hundreds of other spinal cord injured patients in the future.

The phrenic nerve pacing system grew out of almost two decades of research by J. Thomas Mortimer, professor emeritus of biomedical engineering at CWRU, and was implanted in Reeve by a team led by Raymond Onders, assistant professor of surgery, and Anthony DiMarco, professor of medicine and physiology, both at University Hospitals of Cleveland.

At a news conference March 13, held at UHC, Reeve said: "I started out as a patient looking at the big picture, looking at, OK, how long before I get up and walk?â because you're looking at the end result. But I've learned over time that while pursuing that ultimate goal, that incremental steps along the way are very important. ...this ranks very high on the scale as a step forward."

During the news conference, he breathed using the ventilator, not the new device, for which he will need to build more strength in his diaphragm for extended use.

For the procedure, surgeons implanted the device in an outpatient procedure, working through a small laparoscope (a device that lets surgeons peer into and operate through a small incision in the navel) to place electrodes in Reeve's diaphragm muscle. The electrodes were attached through wires under the skin to a small external battery pack that stimulates the muscle and the phrenic nerves, causing the muscle to contract and air to enter the lungs. Contraction of the diaphragm accounts for most of the air intake in normal breathing.

"This device allows patients to breathe and speak more normally, and it increases mobility," DiMarco said.

Freed from a ventilator, which forces air through a hose into the throat and bypasses the nose, Reeve said that he is able to smell the odor of things again. Reeve said that he wanted to test his accuracy in identifying smells again.

"So, I closed my eyes and was breathing on the phrenic pacing device, and they brought in various things to smell, and literally, the first one was coffee. So, I actually woke up and smelled the coffee," he joked.

He correctly guessed the scents of coffee, an orange, a chocolate chip cookie and a mint, but was stumped the next day with a cough drop, still in its wrapper. No one else in the room could guess that one either, he laughed.

Reeve conveyed volumes about the psychological and emotional benefits of the small device through a simple description of the sound of his own breathing.

"During one of the 15-minute sessions, I said, OK, after we're going for a couple of minutes, let's turn off the vent, and we turned off the ventilator, and it was totally quiet in the room. All you could hear was me breathing through my nose. Regular, rhythmic breathing through my nose. I hadn't heard that sound since May of 1995," he said.

Since the implantation of the first device by Onders three years ago, Mortimer and Anthony R. Ignagni, project director and chief biomedical engineer, have improved the operation of the pacing device.

Reeve continued to keep updated on this research and expressed interest in being a study participant about a year ago.

He became a candidate after a thorough evaluation and determination that his phrenic nerve function is normal, as demonstrated in nerve conduction studies and fluoroscopic examination of diaphragm movement. Reeve and the physicians said he was not given any special consideration to enter the study.

February 28, he underwent a four-hour outpatient surgical procedure at UHC to implant four electrodes and lead-wires.

"Our initial test in the operating room to activate Reeve's diaphragm yielded impressive results," Onders said. "As the diaphragm contracted, his lungs filled with air, and the volume of air that was exhaled and measured was certainly adequate for us to believe that this device would provide successful breathing support."

Reeve was eating and talking normally that evening and returned home the following day.

He returned to Cleveland March 9 to begin the reconditioning process of strengthening the diaphragm through a series of intermittent stimulations at the National Institutes of Health-funded CWRU General Clinical Research Center at MetroHealth Medical Center.

"Each electrode is individually evaluated to determine the degree of diaphragm contraction and resulting inspired volume of air," DiMarco said.

Reeve said the sensation of the stimulation felt like the flicking of a finger.

Because the diaphragm is atrophied from disuse, a period of gradually increasing stimulation is necessary to regain normal strength and endurance. Reeve will continue the conditioning process at home, with the ultimate goal of eliminating the need for the mechanical ventilator.

Of the 10,000 new cases of spinal cord injury each year in the United States, about 1,000 patients require mechanical ventilation for some period after injury. Researchers believe that implanting this device shortly after the spinal cord is damaged may enable some to maintain diaphragm muscle strength and prevent atrophy, which develops on mechanical ventilation. Many of these individuals eventually are able to breathe on their own, as the nerves that control breathing recover from the initial injury. Others, like Reeve (perhaps 300 cases each year), would benefit from life-ong breathing support as the implanted device itself activates the nerves that inspire breathing.

"The constant and high cost of care for ventilator dependent patients not only exhausts most insurance policies but contributes to strain on families and caregivers," Reeve said. "Once this procedure receives FDA approval, these patients and their caregivers should be able to achieve significant improvements in their quality of life. Diaphragm pacing unlocks a door to greater independence, one of the most important goals for all people living with disabilities."

The development of the investigational diaphragm pacing system has been a collaborative effort involving numerous physicians and engineers at several institutions in Cleveland, including UHC, CWRU, Louis Stokes Cleveland Department of VA Medical Center and MetroHealth. Onders and DiMarco currently work closely with Ignagni and with Mortimer, who has done his research in the Applied Neural Control Laboratory in the biomedical engineering department. Also involved in the work was Thomas Stellato, professor of surgery, and Michael Nochomovitz, assistant clinical professor of medicine, a key player in the early days. The following graduate students did their graduate work on this project: David Petterson, Brian Schmit, Michael Miller and Harish Aiyar.

"In contributing approximately $1.8 million to this particular project, the VA has taken a leadership role in ensuring the continuity and progression of this research to the benefit of veterans and others with paralysis worldwide," said P. Hunter Peckham, CWRU professor of biomedical engineering. "In fact, the VA has been working on these types of projects for many years and has contributed about $48 million to research and development.

"For example, the applications of electrical signals to muscles in order to control their function was initially supported as exploratory research by both the VA and the National Institutes of Health in the early 1970s," Peckham continued. "The VA has funded research in the development of all these applications and provides a model for how clinical care and research can merge to provide a continuum of research that will benefit the health care of tomorrow."

The investigational diaphragm pacing system, portions of which are patented by CWRU, is now being developed by Synapse Biomedical Ltd. of Cleveland. Funding assistance was provided by the Food and Drug Administration, U.S Surgical Corporation, UHC, the VA and the National Center for Research Resources of the NIH.

Mortimer, who was out of town and unable to attend the news conference, said via e-mail: "A lot of people bought into a vision. They put money, effort and a lot of time into making this vision into a reality. I'm happy to be able to see this happen."

Reeve expressed his deepest gratitude to Onders, DiMarco, CWRU and the other institutions involved.

More information about this clinical investigation can be found at University Hospitals of Cleveland's Web site at www.uhhs.com. People with spinal cord injuries who are interested in becoming candidates for the investigational diaphragm pacing system can call 216-844-UHHS (8447). Researchers hope to study the system on 35 volunteers.

Information about the Christopher Reeve Paralysis Foundation is at www.apacure.com.