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Building a better breathing machine Pitt developing artificial lung that could be used for victims of biological terrorism Monday, March 08, 1999 By Byron Spice, Science Editor, Post-Gazette
The letters were hoaxes. Received last month by dozens of abortion clinics here and across the country, they falsely claimed to contain deadly anthrax spores. But the grisly hate mail imparted at least one valid message: biological terrorism is a growing threat.
It's a warning that is being sounded with increasing frequency, even as emergency and medical experts note that civilian medical centers are ill-prepared for handling casualties of either a biological or chemical weapons attack.
Work on a medical tool that might be used to treat many of these patients is nearing completion at the University of Pittsburgh's McGowan Center for Artificial Organ Development. Called an intravenous membrane oxygenator, or IMO, the device is a temporary artificial lung that can be quickly inserted through the femoral vein in the leg and snaked into the chest cavity.
The oxygenator, about the size of a large breadstick, would sit in the vena cava, the large vein that carries blood back to the heart. The device would pump oxygen to the red blood cells and remove carbon dioxide before the blood ever reached the heart and lungs, giving diseased or damaged lungs a chance to heal.
The artificial lung could be used to treat the roughly 250,000 American adults each year who suffer respiratory distress, a condition in which the lungs become inflamed and cannot function properly. But the U.S. Army is particularly interested in its ability to treat soldiers exposed to biological or chemical weapons. For the past four years, the Defense Department has shouldered the bulk of the development cost, spending about $4 million so far.
Dr. Brack Hattler, the Pitt cardiothoracic surgeon who invented the device, said it is being tested in calves in preparation for trials in human patients.
"Our goal is to have this thing ready for FDA [Food and Drug Administration] trials in 12 months," Hattler said. "We're being pushed from Fort Dietrick [the Army's chemical/biological warfare laboratory in Maryland] to move along with this as quickly as possible."
Certain patients with anthrax might be helped by such a device. A bacterial disease that occurs in sheep and cattle, anthrax can sicken workers who become infected while handling skins or animal products. When spores from the organisms are inhaled, the disease can be lethal, with a death rate of up to 80 percent unless antibiotic therapy is begun promptly.
Hattler said the disease initially causes flu-like symptoms, but after a couple of days a severe pneumonia develops. Patients can have such trouble breathing that they turn blue from the lack of oxygen in their blood. The infection also can break into the bloodstream.
The artificial lung might be used to keep these patients alive long enough for penicillin to rid the body of infection, Hattler said.
A conventional mechanical ventilator can boost blood oxygenation by forcing oxygen into the healthy parts of the lung under high pressure. This only works temporarily, however, because the pressurized gas eventually causes further damage to the lungs.
The implantable oxygenator, however, would reduce or eliminate the need for mechanical ventilation. Hattler said the device has shown it can perform half of the oxygen/carbon dioxide exchange normally performed by healthy lungs at rest.
The device might also be used in other cases of biological weapons that cause severe pneumonia. It would be of little use for nerve gas attacks, but could help patients who inhale "blistering agents," similar to the mustard gas that blistered the lungs and throat linings of doughboys during World War I.
These applications to biological and chemical warfare have always been apparent, Hattler said, but it was two young men gravely injured in an automobile accident in the early 1980s who spurred him to develop the artificial lung.
Hattler, who came to Pittsburgh in 1989, was then a chest surgeon at a hospital in Denver. The legs of both men had been crushed and Hattler was called because the men were having trouble breathing.
"The lungs are kind of a funny organ," he explained. "They will respond to injury that is far removed from the lungs." In this case, muscle proteins released when their legs were crushed had been carried by the bloodstream to their lungs, resulting in lung failure.
Both men were placed on extracorporeal membrane oxygenation, or ECMO, therapy. Similar to the heart-lung machines used to keep people alive during open-heart surgery, the ECMO machine is an external artificial lung through which the body's blood is pumped. It works well enough to keep a patient alive during a four-to-six-hour heart operation, but problems arise over longer periods. The body's immune system reacts against the foreign materials of the ECMO system, causing blood clots and other complications.
Children, whose immune systems are less mature, often do well on ECMO, but about half of all adults die, as did both of Hattler's automobile trauma patients.
So in 1983 Hattler began searching for a better way to help lungs heal. By the mid-1980s, his research team was one of a handful trying to use hundreds of microporous hollow membrane fibers - tiny tubes that, to the naked eye, look like the bristles of a paint brush - to perform blood oxygenation inside the vena cava.
Oxygen would be pumped into some of the porous fibers, while other fibers would be maintained as a vacuum to extract carbon dioxide from the blood.
One of those groups, CardioPulmonics Inc. in Salt Lake City, Utah, developed a device called the intravascular oxygenator, or IVOX, which was clinically tested in 160 patients. Its gas-exchange rate was so low, however, that researchers couldn't show a clear benefit and the device was shelved.
"By 1988, it was clear we would need some active means of involving the blood," said Hattler, whose group is the only one still actively developing an intravascular device. His IMO design was similar to the IVOX but with a crucial difference - a balloon at its center that could be inflated and deflated, helping to move blood past the fibers.
William Federspiel, the bioengineer who directs the McGowan Center's artificial lung lab, said the device now uses 700 to 800 fibers that are woven into a fabric that surrounds the central balloon. It is able to exchange two or three times as much oxygen and carbon dioxide as the IVOX, he noted, more than enough to show clinical benefit.
"We'd like to put the respirator people out of business eventually," said Federspiel, expressing hope that the device might eliminate the need for mechanical ventilators for many patients.
The disposable unit might cost $2,000, a fraction of the cost of ECMO, he added.
The device, when collapsed, is small enough to fit in the half-inch-diameter femoral vein in the leg. Once in place in the vena cava, the inflated device assumes its usual "breadstick" size. To many laymen, it seems surprisingly big for something that must fit inside a vein, but Hattler, playing along with the food analogies, points out that the vena cava is about the size of a Hungarian sausage and more than capable of accommodating the artificial lung.
The disposable unit could remain in place two to three weeks. Patients would need to be on anti-coagulant therapy to minimize the risk of blood clots forming on the device. Hattler said the team also is studying coatings - silicone polymers bonded to heparin, an anti-coagulant - that would reduce this risk.
Fred Pearce, a research physiologist and chief of resuscitative medicine at Walter Reed Army Institute of Research in Washington, D.C., admitted he was skeptical about the IMO's capability when the Army began sponsoring its development four years ago. But the Pitt researchers have made a breakthrough in improving the oxygen exchange rates "and we're hopeful we might be able to get a higher percentage."
Another major concern is to make it easy to insert - preferably easy enough for a paramedic to put in place. So far, that appears possible.
The Army would use the device for biological and chemical weapons casualties, as well as any other battlefield injury that requires respiratory support. The only other technology remotely comparable, Pearce said, would be fluid ventilation. That technique delivers oxygen by filling the lungs with an oxygen-carrying fluorocarbon solution.
It's a procedure that has worked in infants, but that Pearce fears may not be suitable to the battlefield. "We need to have something that's very simple," he explained. It looks like the IMO, once in place, would be easier to automate.
Eventually, the IMO might be incorporated into the LSTAT, an enclosed military stretcher that serves as a mobile intensive care unit used to keep patients alive for 12 to 16 hours while they are transported to a hospital for definitive care.
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