Mending Little Hearts
The pCAS pump and other pediatric heart devices under development by U of L's George Pantalos and Colleagues offer hope for thousands of infants born each year with congenital heart defects.
George Pantalos, a slender man in blue scrubs with an embroidered Snoopy on the breast pocket, hands me a small, round disc of transparent plastic called the pCAS. We're sitting in his office in the U of L Health Sciences Center. It's a generously-sized office, though crowded with piles of books, papers, journals, empty Dr. Pepper cans and equipment.
I reach over to take the device, gingerly. The pCAS pump (pronounced"Pee-kaz" for "Pediatric Cardiopulmonary Assist System"), is essentially the working end of a mini heart/lung machine. It's a bit hefty, and about the diameter of a large yo-yo. Two tapered, flexible tubes, also transparent, called cannula, reach out from the disc and vibrate slightly, like insect antennae.
Pantalos, professor of surgery and bioengineering at U of L, is a member of the Cardiovascular Innovation Institute, a partnership between U of L and Jewish Hospital dedicated to supporting the development, testing and clinical trials of new heart assist devices. Pantalos explains that this piece of clear plastic, or something like that, may someday save the lives of infants and children whose hearts can't function on their own. That inability to function may occur for many reasons, including surgery to correct congenital heart defects. "The surgery may correct the defect, but the heart becomes injured or stunned and can't be weaned off the heart/lung machine at the time," Pantalos explains.
The pCAS is being developed jointly by U of L and a University of Pittsburgh spin-off, Ension Inc., that is under contract with the National Institutes of Health. The NIH began infusing the project last April with $3.7 million. The funds, and an additional $1.1 million NIH Small Business Innovation Research grant, will incubate the tiny heart/lung machine during its first five years. Enough time, Pantalos hopes, to see the project gain FDA approval for clinical trials.
A $5 billion gift recently provided for cardiac research by Kosair Charities Foundation also may help the pCAS effort, Pantalos adds.
There's great need for such a device. According to the American Heart Association, about nine out of every 1,000 American babies are born with congenital heart defects, or about 36,000 a year. Studies suggest that 9,600 of these infants will require immediate surgery or will die before their first birthday. Despite surgical advances, the mortality rate is still as high as 20 percent for some conditions.
That's where the pCAS comes in.
"It's a temporary devise, used up to two months until the heart and lungs recover and stabilize," Pantalos explains. Or, for heart repairs that are done in stages, "to sustain circulation until the next step, to get a donor for transplant or sustain the patient until the next corrective stage."
Mark Gartner, Ension's president, says U of L was "a natural fit" as a research partner.
"We sought expertise in pediatric devices, a strong animal evaluation program and a strong clinical program to give the appropriate insights," he says. And "Dr. Pantalos is a recognized leader in pediatric medical devices."
The pCAS actually was born as a device for adults that Ension is still developing. That version is larger; four inches in diameter, and pumps a greater volume of blood, from five to seven liters a minute.
Though it served as the basis for the infant version, Pantalos explains that you can't just scale a pump down to child size and expect it to work.
In comparison, the infant version is no wider than the top of the Styrofoam cup of decaf that Pantalos had handed me moments before. And it is mundane-looking for a multi-million dollar future high-tech medical miracle. Two tubes and a disc containing a square of white mesh and a rotor that turns, called an impeller--just this, to help mend a tiny broken heart.
But in scientific research no less than anything else in life, looks are often deceiving. That's apparent as Pantalos begins explaining the complex science involved in getting a pump and some plumbing to flow enough oxygen-rich blood through a patient to sustain life.
Unlike some models being developed for implantation in the abdomen, the pCAS will be used, in the lingo, extracorporeally. That is, the pump will sit in a vest snugly comfortable against the patient's chest. The cannula will be sent into the abdomen and attached to the circulatory system, one to deliver the oxygenated blood, and the other to return the oxygen-depleted blood, remove carbon dioxide and re-oxygenate it.
The inner white mesh actually is made up of hollow fibers, "like the oxygenator of a heart/lung machine," Pantalos says. These fibers remove excess carbon dioxide. Combining gas exchange and blood pumping in one device is a great advantage.
"Sometimes infants and children need cardiac support and later develop the need for pulmonary support. All you have to do is change the way you use the device. You don't have to switch devices or add another one."
Getting this to work optimally isn't as easy as it sounds. So far, the best impeller rpm for exchanging gases is too high to move blood efficiently through the patient's body. The speed can also injure delicate blood cells.
Greg Johnson, Ension's technical director and the lead bioengineer for the pCAS project, explains that "with a water pump you don't have to care about how much you beat up the water that's going through it." However, "pumping blood is a very unique application to pumping technology in general because you have to be very gentle with the fluid."
These and many other meticulous design details challenge the team and provide an example of how diverse specialties such as surgery, bioengineering and computer science work together to perfect a project.
Pantalos' team with a mock circulatory system.
For instance, two specialists at the software and consulting firm, Fluent Inc., put the pCAS through its paces using a science called computational fluid dynamics. This computer-generated plane is a virtual wind tunnel. Such studies will help researchers fine-tune the flow.
Even something as apparently simple as the size of the cannulae presents design difficulties. Photos of one of the experimental surgeries on piglets reveal the almost impossibly tiny attachments. But the results suggested to Pantalos that these tubes needed to be even smaller.
"So often the focus is on the pump. But if you can't connect it effectively to the heart you are not going to be able to help the patient."
Yet these changes start a cascade of design adjustments.
Too much flow resistance, for instance, may increase the power the pump needs to operate, which then may change the design of the pump and even the size and power requirements of backup batteries.
Another change in the cannulae that Pantalos recommended was prompted by the need to reduce the risk of infection--always a concern, but an even greater one when they could be in contact with skin for two months.
To reduce this risk, he's recommended a skin-like covering for those contact interfaces. It's being developed by Seare Biomatrix Systems of Salt Lake City, an Ension contractor.
Pantalos digs into a box of assorted artificial hearts, cardiac assist devices and medical plumbing for a sample. The box is private collection of a fascinating era in medical engineering.
"I refer to myself as a cardiovascular explorer," he says, handing me first a Jarvik 7 and then an ABIOMED AbioCor artificial heart. The latter model was akin to the one he helped implant in Robert Tools in 2001. "I've been doing circulatory support for over two decades."
According To The American Heart Association, Approximately Nine Out Of Every 1,000 American Babies Are Born With Congenital Heart Defects, Or About 36,000 Per Year. Several Studies Suggest That 9,600 Of These Infants Will Require Immediate Surgery Or Will Die Of Their Condition Before They Reach Their First Birthday.
After rummaging some more, he finally hands over a small square of silicone. It does feel remarkably like skin.
"Dr. Bill Seare's matrix provides soft tissue ingrowth for anchoring the cannulae," he says, adding that when the pCAS needs to be removed a surgeon "can dissect through it like soft tissue, and it promotes vascular generation," which is important for keeping the skin at the contact site healthy.
The infection problem, at least, may be nearly solved, but the list of requirements for this device are dizzying. Among them, Johnson tells me it has to be designed to set up in 30 minutes, require a reasonably small volume of blood to prime the pump and have adequate battery backup to transport patients. Also, being a "disposable, single-use device designed to last up to three months," it needs to be cheap enough so that insurance companies will cover it--say about $1,500.
Finally, the assist system must have a user interface (i.e. buttons, dials, readouts) clear enough so the medical team can work it efficiently. Designing the controller hardware and overseeing the software development is the job of Ension's Chris Lucci.
I view the controller, a simple metal box, when Pantalos escorts me to a room containing what he refers to as the "plastic patient." It sits next to a tabletop full of tubing, filters, housings, clamps, electric leads and other assorted paraphernalia.
Not all design and testing can be accomplished with computer modeling and animal experiments. The plastic patient is a mock pediatric circulation system that mimics the physiological response of a 1-year old child. This pulsating model used by U of L grad student Jeff Colyer for his thesis research is sometimes filled with water, sometimes with messy glycerin fluid that is close to the viscosity of blood. The pCAS is connected to it.
"We make the left ventricle go into failure, gradually turn on the device and look at the response," Pantalos says.
Guruprasad Anapathur Giridharan, a U of L researcher, also helps developments by modeling the circulation system on a computer.
Thus, when Ension's Johnson remarks that the pCAS development is "a major team effort" he is not exaggerating. The acknowledgements section of the contract lists 32 people. Yet, there are more.
"It takes a big team to make a small heart," Pantalos explains. Some of these other key players in the feedback development loop include pediatric surgeons Earl Austin and Mike Mitchell (both jointly appointed to U of L and Kosair Children's Research Hospital), Kosair perfusionist Tony Cromer (a perfusionist operates a heart/lung machine during surgery), and Scott McClure, Kosair's ECMO coordinator and U of L veterinary surgeon Ken Litwak, who will conduct the chronic animal evaluation experiments.
The ECMO, or extra-corporeal membrane oxygenator, is a complex setup that does the work the pCAS may eventually do.
Even with all this expertise, Pantalos says a lot of "bugs" need to be worked out before the team applies to the FDA for a clinical trial in four or five years.
Though many obstacles remain to be surmounted, as I take a last look around Pantalos' office, I can't help thinking this place has perhaps a better chance than most to give birth to a life-saving pediatric cardiopulmonary assist device.
A fingerpainting made by one of Pantalos' daughters is taped to a file cabinet. On one wall hangs a photo of a quilt created as a fundraiser by Mended Hearts, a patient support group. Pantalos sewed on of the quilt squares himself.
"My mom taught me to sew when I was young," he tells me.