Oriented to Thoracic Transplant Recipients -- April 2000

Growing Hearts From Scratch

Within a decade, scientists aim to create transplantable human hearts that could be stocked on hospital shelves. Dr. Joseph Vacanti and Robert Langer came up with the idea of using biodegradable scaffoldings to grow tissues.
By Dawn Stover

For fun, Bill Dreyer liked to ski off 30- foot cliffs, race in triathions, and hunt elk with a bow he had made himself. But Dreyer, a 49-year-old chiropractor who lived in Anchorage, Alaska, didn’t enjoy any of those things during his last year, which he spent in Arlington, Washington, waiting for a heart transplant. Dreyer died November 17, 1999, of heart failure caused by a rare disease.

Across the United States, more than 4,000 patients are currently on a waiting list for a heart transplant. Only the sickest patients make the list, and only about 2,300 of them will be lucky enough to get a heart this year, according to statistics collected by the United Network for Organ Sharing. Many other patients, like Dreyer, will die waiting. Dreyer’s wish was for more people to register as organ donors.

But even that may not solve the problem, because the demand for transplantable organs is rising about 15 percent annually. While some surgeons are looking to artificial hearts or animal organs as transplants, others are turning to tissue engineering. In this new field, doctors have joined forces with engineers and biochemists to assemble living cells into spare parts for the human body.
Perhaps the most far-reaching project is an initiative called Living Implants From Engineering (LIFE). Led by Michael Sefton, director of the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, LIFE kicked off in June 1998 with the goal of creating “an essentially unlimited supply of human vital organs for transplantation.”

The LIFE consortium- which includes researchers from MIT, Massachusetts General Hospital, the Pittsburgh Tissue Engineering Initiative, and other facilities in the United States, Canada, Europe, and Japan - plans to start by building a heart within a decade. Sefton estimates that creating a functioning heart for pre-clinical
testing will cost $5 billion.

The ultimate goal is to create what Sefton calls a “heart in a box,” a transplantable heart that could be stored at hospitals until needed, alongside the syringes and scalpels. “It’s on the ambitious side of realistic,” he admits.
It might be easier to build a liver or a kidney, but that’s why Sefton chose the heart. “If we can figure out how to engineer a heart, the rest will follow,” he says. The other big reason is that cardiovascular disease is the leading cause of death in North America.

Among the LIFE partners are the fathers of tissue engineering: Dr. Joseph Vacanti, a professor of surgery at the Harvard Medical School and Massachusetts General Hospital; and Robert Langer, a chemical engineering professor at MIT. In the 1 980s, they devised a method of growing cells on mesh scaffoldings that slowly disintegrate as the cells multiply.

First, researchers create a scaffolding with the three-dimensional shape of the tissue they are engineering. Scaffoldings are typically made from biodegradable polymers such as polylactic acid and polyglycolic acid, originally developed for sutures.

The next step is to seed the scaffolding with cells taken from the type of organ the researchers hope to create. The cell-studded scaffolding is placed in a bioreactor, an incubator of sorts, which is kept at body temperature. In-side the bioreactor, an oxygenated mixture of nutrients that Vacanti calls “chicken soup for the heart” is pumped around and through the scaffolding. The cells divide, and secrete proteins and growth factors that bind them together to form living tissue.
Vacanti has used this method to create 27 different types of tissue in his lab alone. The first useful products were small sheets of skin, and pieces of cartilage fashioned into recognizable shapes such as noses and ears.

Other researchers have created whole organs. At Harvard Medical School, Dr. Anthony Atala has grown bladders for dogs, using their own cells. Implanted back into the dogs, they work for as long as a year. Eventually, bladders grown from human fetal cells may help patients with urological problems such as incontinence.
But tissue engineers are now setting their sights on more complex organs such as the heart. Researchers have already created rudimentary blood vessels, valves, and muscles. Making these components perform as well as natural tissues, and bringing them together in a single organ, will be an enormous challenge. “Instead of talking about making a trunk of a tree, or a branch of a tree, we’re talking about making a whole tree,” says Vacanti.

More than five years ago, Drs. Lisa Freed and Gordana Vunjak-Novakovic of MIT seeded heart cells onto a scaffolding in a bioreactor. The tissue they created was smaller than an aspirin. When they applied electrical signals to it, the cells began to beat as one. “It was my most awesome laboratory moment ever,” recalls Freed, a principal research scientist in the Harvard-MIT Division of Health Sciences and Technology. “No one had ever done this before.”
Although this and subsequent “cardiac constructs” resemble heart tissue, they don’t have blood vessels running through them. For large chunks of tissue, or whole organs, a blood supply is a necessity. To create blood vessels in heart tissue, researchers could build a scaffolding with a vessel network in place, or they could coat the scaffolding with growth factors that trigger blood vessel formation.

Several research teams have created “artificial arteries” by growing smooth muscle cells on a polymer tube, and then coating the inside of the tube with epithelial lining cells. In one case, researchers implanted an engineered pulmonary artery in a sheep, and it not only functioned properly for six months, but even grew over time.

Dr. Laura Niklason, an anesthesiologist and biomedical engineer at Duke University, takes the raw materials for engineered arteries from pigs and implants the arteries back into the pigs a week later. She has discovered that the arteries develop better if blood is pulsed through them as they grow. Arteries made by the pulsing method last for a month or more; without the pulsing, they clog after a few weeks.

Clogging is an even more serious problem for smaller blood vessels. To create the blood supply for a heart, researchers will also have to design tiny, branching capillaries. The biotechnology company Organogenesis in Canton, Massachusetts, is working on one possible solution: creating blood vessels from natural collagen (the body’s connective tissue) coated with a layer of anticoagulant that prevents clogs. Once implanted, the tubes attract the body’s own vascular cells and grow into normal blood vessels.
Meanwhile, others are testing methods for creating heart valves, which direct the flow of blood through the heart. A team led by Dr.Simon Hoerstrup at Children’s Hospital in Boston has implanted experimental valves in six lambs; the valves functioned for several months.

Valves and other body parts grown in the lab are generally not as strong as those nature makes, but scientists are working on that. One idea, which a group led by Robert Nerem at Georgia Tech is testing, is to force pressurized air through developing blood vessels at regular intervals.

Another possibility is to regularly stretch the tubes as they develop, mimicking what happens to natural blood vessels as fluid pulses through them. David Mooney, an associate professor of biologic and materials science at the University of Michigan, is seeding cells onto scaffoldings clamped to mechanical devices that repeatedly tug on the scaffoldings as the tissue develops. He has learned that the blood vessel cells align in a more orderly fashion when exposed to strain for several weeks. Mooney also discovered that he could get increased production of structural proteins that make the tissue stronger, but only with some types of scaffolding material. “We were able to demonstrate that mechanical signals must come through certain molecules to which the cells attach,” Mooney explains. The challenge for the future is to customize the biodegradable materials used in scaffoldings to provide exactly the right trigger for cells to grow.

Vacanti is also looking at a new way of fabricating scaffoldings. His idea is to use microfabrication techniques borrowed from the computer industry to make a “tissue on a chip,” with structures that are fractions of a micron in size, but are made from a biomaterial instead of silicon.

Even if Vacanti and others in the field solve the challenges of growing a heart, they’ll have to find a way to keep the tissue alive until it’s needed for transplant. The most likely method is cryopreservation - freezing the heart in a fluid that protects it from damage. The difficulty comes when you try to thaw out the cells without cracking them. “Storing the heart is not going to be a simple problem,” concedes Sefton. And unless a heart in a box can be made from a patient’s own cells, recipients will have the same problems of immune rejection that they encounter with today’s transplants.

In the end, the biggest limiting factor may be money, not technology. Although the LIFE initiative has received some funding from the National Institutes of Health, the coffers don’t contain anywhere near the $5 billion needed.
On the other hand, there is potentially a lot of money to be made from engineered hearts, livers, kidneys, skin, and even dental fillings.

Cardiovascular disease alone is estimated to take a toll of $175 billion annually in the United States.

Even if the partners can’t create an entire heart within a decade, partial victories could be valuable. “We all agree that the heart is attractive because it has modular components,” says Vacanti. An engineered coronary artery, for example, could eliminate the need to remove a major vein from a patient’s leg for bypass surgery. An engineered chunk of heart tissue could be useful for testing drugs. Already, one potential spin-off is a cardiac “patch” that could replace tissue damaged by a heart attack. Researchers at the University of Washington Engineered Biomaterials Center in Seattle are talking about developing a ventricular patch, says Director Buddy Rather. “It’s a living Band-Aid,” he explains.
Ultimately, stem cells - the precursor cells that differentiate to form various organs - may make the job of building a heart easier. If scientists can figure out the biochemical triggers that cause stem cells to turn into heart cells, for example, they might even be able to grow a heart without a scaffolding. The best solution of all would be to create a heart from a patient’s own stem cells, ensuring that rejection would not be a problem.

Unlike a mechanical heart, a heart made from human cells will be able to grow and adapt. “That’s our ultimate objective,” says Vacanti, “to find a biological replacement that can function as living tissue.”

Popular Science, April, 2000 pp.46-50

The Fine Print

Engineered tissues, such as this heart valve, can be grown on biodegradable scaffoldings created by a 3-D printer.
by Dawn Stover

To grow the components of a human heart in the lab, some researchers are turning to high-tech equipment originally designed for completely different purposes. For example, some bioreactors used to incubate engineered tissues are derived from a rotating-wall bioreactor developed by NASA for microgravity experiments. The rotation ensures that nutrients are evenly distributed throughout the scaffoldings upon which heart cells are grown.

Creating the biodegradable scaffoldings that support growing cells is ajob made for another repurposed tool: a three-dimensional printer, or 3DP. Patented in 1993 by a group at MIT led by mechanical engineer Emanuel Sachs, the 3DP was originally developed to create ceramic molds for metal castings. It is also widely used to create instant prototypes of parts for airplanes and other machines.

Biomedical engineer Linda Griffith of MIT is using the 3DP to make body parts instead. First, she creates a computerized blueprint for the scaffolding and sends it to the 3DP. The printer’s multiple ink-jet nozzles then spit out microdrops of a glue-like binder onto an ultrathin layer of powdered biodegradable polymer. The microdrops bind with the powder and solidify. The platform on which the scaffolding is being constructed then descends ever so slightly (less than the width of a human hair), a new layer of powder is spread, and a second pattern of binder is sprayed onto the powder. This process is repeated, layer upon layer, in a sequence directed by the blueprint, until the entire structure is complete.

Popular Science, April, 2000 P. 50

New Hampshire Marathoner Won’t Be Slowed Down By New Heart

by Michael Lasalandra

A 28-year-old New Hampshire woman intends to become the first female heart transplant patient to run a marathon when she enters this year’s Boston event. Danalyn Adams Scharf of Dover and an employee of the American Heart Association had her lifesaving transplant three years ago.

Running the marathon “has always been a goal of mine,” she said. She also said she wants to help raise awareness of the need for organ donation “and to let people see that you can be the same healthy person as before.”

Scharf said she used to run prior to her operation, but she had never before run a marathon, let alone the especially demanding Boston Marathon. She’s been in training for a while now and says she’s ready.

“It’s going well,” she said. “I’m running with my husband, Matt, and we’re going to complete it.”

Scharf has the green light from her doctors to give the grueling 26.2-mile event a try on April 17. “We’ve looked at it carefully and we don’t think it’s a problem,” said Dr. David Adams, associate chief of cardiac surgery at Brigham and Women’s Hospital, who performed the transplant operation in March 1997. Adams said he and the other doctors who have been involved in her care are thrilled that Scharf is going to give the race a shot.

“She’s a remarkable person,” he said. “She’s really rejoined her life in a normal way. Running a marathon after a heart transplant is an exclamation point for what has really been a marathon for her the past few years.” He noted Scharf had suffered from viral myocarditis, a deadly inflammation of the heart muscle tissue. “She suffered a cardiac arrest,” he said. “It was the most serious sort of condition.”

Following her cardiac arrest, Scharf was put on a ventricular assist device - a kind of artificial heart - for several weeks. The device, BVS 5000, manufactured by Abiomed Inc. of Danvers, is known as a “bridge to transplantation.” It pumped blood for her while she waited for a transplant organ to become available. “Only half of the patients who go on these devices ever get off of them,” he said. “And, of those, only half leave the hospital. It was a long road back for her.”

Dr. John Jarcho, her cardiologist, said the marathon run will be demanding, and she will have to be especially careful that she doesn’t get dehydrated. In addition, her bones and connective tissues are at risk for injury because she is taking steroids to keep her body from rejecting her new heart. “But her heart itself is in very good condition,” he said. “We would not expect her to suffer a heart injury.”

Still, she will be running with one of the hospital’s cardiac nurses with whom she became friendly during her hospitalization. “Beyond that, we are taking no special precautions,” Jarcho said.

A native of New Jersey, Scharf once worked as a newspaper reporter in Maine and now runs youth programs for the AHA in Massachusetts and New Hampshire. She also often lectures to school assemblies about her transplant. She will be running as part of a 125-member team from Brigham and Women’s and will be raising money for the Heart Hope Fund, to support transplant research. “I’m really excited,” she said. “When I got my card in the mail from the (Boston Athletic Association), my whole body got all warm and tingly and nervous.”

Boston Herald 4/6/2000 Contributed by Tx Dave Cannavo


In the March issue of UpBeat a phrase fell out of the system someplace during transmission. UpBeat is now totally upbeat and very comparable to USA Today in that the content is gathered and written here in the swamps of Tidewater Virginia. Then all the material is transmitted via e-mail to our loyal “Publisher”, Jody Roginson, in Seattle. Jody constructs the page layouts and tries to make everything fit. When she’s done the best she can with what I gave her to work with, she again transmits it via e-mail to our long time printer, Print N Save, in our mutual old work town of Anaheim, CA.

Now back to the original point: At the end of my “editorial” regarding how lucky those recipients to follow us under the new drug regimen were going to be, I signed at the end: Don Marshall, Tx Class of ‘88, “We did it the hard way.” Somehow the last phrase never made it, but I felt that way when I wrote the statement, and I still do. Now there’s the motto of a new Tx club if I ever saw such a thing!

By the way, Jody Roginson has worked with UpBeat ever since we started formally printing it, so she’s well used to working with transplant type things and volunteer groups. If you have a brochure, flyer, newsletter, that need some creative attention she has now started her own firm in Seattle

“Specializing in Creating the Things You Need.” She can be reached at 206-297-8295, orjodyroginson@earthlink.net. Your project can all be handled via e-mail or phone, including printing or other.

Sick transit A packed jumbo jet. Recirculated air. And the bozo in the next row is coughing and sneezing up a storm.

You’re flying the unfriendly skies and, wouldn’t you know it, if your immune system is weak, you could end up taking some nasty viruses home with you.

But don’t blame the poor ventilation.

“It’s a question of luck,” says Dr. Bradley Connor, medical director of the New York Center for Travel and Tropical Medicine.

Passengers are most likely to catch the influenza virus from someone infected who is sitting - and sneezing - very close to them, whether they’re on a plane, train or automobile. At 30,000 feet up, that means virtually anyone within a two-row radius is capable of slipping you the flu, says Connor. This is especially true if you’re a stressed out business traveler deprived of sleep.

Air conditioning systems don’t seem to spread viruses throughout the plane, Connor says. That doesn’t mean, however, that if everyone sitting near you looks healthy you’re safe.

Sometimes the communal blankets or pillows passed out on planes may have gone a few flights between washings, allowing them to harbor viruses, fungi and lice.

“Air travel and the risk of infectious disease, viruses, that kind of thing, is over blown,” says Connor, but “it does stand to reason if the pillow looks well-worn.. .you may want to think twice about using it.”

Julie Sevrens San Jose Mercury News

Contributed by Tx Penny Toni. Santa Cruz

I have had just one book review of the new book mentioned in the last issue, Where There’s Love.... There’s Miracles, written by Terry Lemons, wife of Tx Wes Lemons of Victorville, CA. The review simply stated was, “My wife bought the book, brought it home, and didn’t put it down until she had finished it.” The book is $11.95 plus $4.95 for shipping and handling from Lemons Publishing, P.O. Box 3594, Victorville, CA 92393-3594. Residents of California add 93 cents tax.

Erratum: The opening sentence of the March issue contained the phrase, “reduce the chance of rejection In heart transplant pawns shout increasing their risk of infections If anyone knows what that’s supposed to mean, please keep it to yourself, it’s obviously a code.

April 9, 2000

Hi Don!

My name is Danalyn Adams Scharf, the heart transplant recipient gearing up for the Boston Marathon on Monday, 17 April, also Patriot’s Day. I’m running for Brigham & Women’s Hospital in Boston (where I was transplanted three years ago on 17 March) and the money I raise for the hospital is earmarked for the Heart Hope Fund, established by my cardiac surgeon last year for transplant research at the hospital and for organ donation awareness in the Boston area. Donations would be greatly appreciated. Not only will the money help others, but it would also help the many heart transplant recipients already living with new organs.

As a former newspaper reporter who now works for the American Heart Association, I’d love to write a short piece for your newsletter about my marathon experience, if you’re interested. Anyway, here is my address and thanks so much for thinking of me.

DOVER, NH 03820

Checks should be made out to
Brigham & Women’s Hospital
and are fully tax-deductible.
They will be accepted up to June 1, 2000.

Thank you, Don!
Danalyn Adams Scharf, Youth Programs Specialist American Heart Association

GO DANALYN!! DM - My check is in the mail. As one who finds Cardiac Rehab. a boring grind, I shall await the story of one who obviously has the right attitude!



Hope for Transplant Patients

Future victims of the organ-transplant crunch received modest good news this week from a meeting in Texas and a pigsty in Virginia. In the first case, the United Network for Organ Sharing, which allocates the organs collected by 60 procurement programs, agreed Monday to improve the way it distributes livers..

In the second case scientists announced They had cloned five piglets - a heady step toward the far-off day when pigs can be used to grow organs and tissues for human use.

Right now, about 68,000 people sit on various transplant waiting lists, and many aren’t going to make it. In 1998, 4,800 people died waiting. That statistic yells out the need for better organ-donor recruitment. But it speaks with equal to the urgency of making more efficient use of scarce available organs.

Presently, organs are doled out on the basis of murky medical definitions and arbitrary regional boundaries, with occasionally unfair results. A mildly sick patient in one region might get a new organ, while a critically ill patient 100 miles away dies waiting. Two years ago, federal regulators ordered reforms.

It hasn’t been entirely a noble effort since then. Many. doctors hospitals and lawmakers objected, fearing they would lose cherished local transplant facilities. Congress twice ordered delays, and even now, Wisconsin officials are threatening to sue. Moreover, the latest revisions cover only livers: Patients needing other organs will wait longer.

All of which makes the piglets look pretty good. There are huge obstacles to the day when herds of swine provide unlimited organs for human transplant. As long as there aren’t enough donated organs, though, a pig’s heart is better than no heart at all.

Plainly, the best news would be donation rates so high that both turf battles and cloning are made irrelevant. In the meantime, however, transplant candidates can take at least faint comfort from the knowledge that reforms are in the works, and that transplant piggies are one step closer to market.

USA Today Editorial 3/16/00

Dolly Creators Claim Cloning Pigs

By Kia Shant’e Breaux - Associated Press Writer

BLACKSBURG, Va. (AP 3/14/00)—The company that cloned Dolly the sheep has produced the first cloned pigs, five little piggies named Millie, Christa, Alexis, Carrel and Dotcom that raise hopes for a new source of transplants for humans.

“I think this is a big step forward they’ve made. I applaud it,” said Dr. Fritz Bach of Harvard Medical School, who studies genetic and immunological aspects of transplants from animals to people and was not involved in the cloning.

The piglets, delivered by Caesarian section March 5 at the Virginia-Maryland College of Veterinary Medicine, were produced by a subsidiary of PPL Therapeutics of Edinburgh, Scotland, which nearly four years ago created Dolly, the world’s first clone of an adult mammal.

“The birth of these pigs is a very significant accomplishment,” Dave Ayares, PPL’s vice president of research, said at a news conference Tuesday. “It has the potential to essentially revolutionize the transplantation field.”

The five female pigs were cloned from an adult sow named Destiny using a slightly different technique than the one that produced Dolly.

Independent tests of the DNA of the piglets confirmed they were clones of the sow, the company said.

The identical baby pigs playfully wrestled and nibbled on each other’s ears inside a wooden pen at the news conference. Their mother was not present.

PPL touted the clones as a major step toward achieving its xenograft objectives, which would create genetically altered pigs whose organs and cells could be successfully transplanted in humans. Pigs are physiologically one of the closest animals to humans.

Imutran, a Cambridge, England-based company pursuing similar research, called PPL’s announcement “interesting news.”

“It is potentially a useful technology to develop new lines of pigs for (transplant),” the company said. “However, the next step is to see if the technology can be applied to developing genetically modified animals whose organs can be transplanted into humans without being rejected.”

The idea of using animal organs for transplant, known as xenotransplantation, is controversial because some believe illnesses could cross from pigs to humans.

PPL scientists plan to try to eliminate a gene responsible for incorporating in pig cells a sugar group recognized by the human immune system as foreign. The gene triggers an immune response in the human body, prompting it to reject the organ.

PPL said transplantation of genetically altered pig organs could be tested on humans in four years and that analysts believe the market for them could be worth $6 billion for solid organs alone. Other uses include cellular therapies such as transplantable cells that produce insulin for treatment of diabetes.

“We hope in the very near-term to overcome the shortage of human organs,” said Ayares, who noted ultrasounds performed Tuesday confirmed additional pig cloning pregnancies at the company’s farm in Blacksburg.

The only connection the births have to the veterinary school at Virginia Tech is that the university provided the clinical services for the delivery. All of the research was conducted and funded by PPL.

Despite the potential solution for organ shortages, the pig cloning drew criticism from animal rights activists.

“There’s always a reason given to validate these Frankenstein-like experiments,” said Lisa Lange, a spokeswoman for Norfolk- based People for the Ethical Treatment of Animals.

“Animals are not test tubes with tails and they are not commodities to be marketed.”

Ayares countered that pigs for years have been raised and slaughtered for food.

“I don’t think our pigs are being mistreated,” Ayares said. “They live better than any other pigs.”

The names of the first cloned piglets each have their own significance. Millie was named for the millennium. Christa, Alexis and Carrel were named after Dr. Christiaan Barnard, who performed the first human heart transplant, and Dr. Alexis Carrel, who won the Nobel prize in 1912 for his work in the field of transplantation.

And Dotcom?

“Any association with dotcoms right now seems to have a very positive influence on a company’s valuation,” said Ron James, PPL’s managing director.

Congress Debates Transplant Dispute

Filched from: bit.listserv.transplant where it was posted by Tx Jim Gleason of PA with the comment, “After so much news, this piece seemed to give a clear summary...
By Laura Meckler

Washington (AP 4/4/00) After two years of public struggle, warring parties are edging toward common ground in a dispute over which transplant patients will get first chance at donated organs.

But a contentious debate beginning today in the House and a federal lawsuit in Wisconsin make it clear that solving this emotional and bitter argument will not be simple.

Both sides appear weary from the protracted battle. “It’s time to get on with it already,” said a frustrated Dr. Jeffrey Reese, a kidney surgeon from the University of Vermont. “Let’s get onto the next issue of increasing (organ) donation.”

He and most others are looking to a pair of leaders on health care, Sens. Bill Frist and Edward Kennedy, who are working on compromise legislation that all parties can accept.

“We honestly are trying to work this thing out in a civil manner,” said Mark Rosenker of the United Network for Organ Sharing, the private firm that runs the nation’s transplant network under a government contract and has been battling the Clinton administration over a new distribution system for organs.

The other side agrees. It’s as if Kennedy and Frist found the transplant world in a shaky, crowded rowboat with everyone trying to stand up at once, said Charlie Fiske, who heads a patient group. “The Frist Kennedy people are saying, ‘Put your lifejackets on. Please sit down.”

But while Frist, R-Tenn., and Kennedy, D-Mass., prepare to introduce their compromise as soon as Wednesday, the House is taking a much different path. The House bill being debated today takes the transplant network’s side on virtually every point of dispute. With heavy lobbying under way by both sides, the bill was expected to pass.

At the heart of the issue are two questions: How should a nation accustomed to the finest medical resources divvy up the scarce number of livers, hearts, kidneys and other organs donated for transplant? And, equally important, who has
final say over what that policy will be?

The current system relies heavily on geography, with patients getting the first chance at organs donated locally, even if someone sicker is just over the arbitrarily drawn border.

But in April 1998, the Department of Health and Human Services ordered the network to create a new system that directed more of the donated organs to the sickest patients. Patients are dying simply because of where they live, HHS argued.

Under the current system. a liver donated in New Jersey will go to a relatively healthy patient in another part of the state before it crosses the Hudson River to save a dying patient in New York City.

The network and many transplant centers objected on two fronts: They didn’t want to overhaul their local-first system, which many centers rely on for a reliable - albeit inadequate - supply of organs. And they didn’t want HHS telling them what to do. They launched an intense lobbying effort, which succeeded in persuading Congress to keep the regulations in limbo for nearly two years.

Last month, the HHS rules finally took effect. As directed, the transplant network promised to develop a new policy for distributing livers, the organ that’s generated the most controversy. It already had begun to break down geographic barriers for the very sickest patients. A new system, they promised, will continue to broaden the distribution areas. And it will be based on more objective criteria, meaning the sickest patients will rise to the top of the waiting liist more quickly.

HHS was cautiously optimistic.

Meanwhile, there was hopeful news from the Senate. Frist and Kennedy, who led their respective parties in the highly charged debate over the patients’ bill of rights, came together to look for common ground on the transplant issue. Their bill, like the one being debated in the House today, gets at the underlying issue of who has the power to set policy.

But while the House bill strips HHS of all its authority over substantive policy issues, the Kennedy-Frist measure seeks a compromise.

The toughest issue is whether the HHS secretary should have final say over what the nation’s transplant policy should be. The Senate bill would force the secretary to share that final say with an advisory board made up of experts, administration and congressional officials said Monday.

But first comes today’s debate over the House bill. President Clinton’s advisers have threatened a veto, arguing the measure is unconstitutional because it gives a private body the power to set federal rules that would be enforceable by law.
Meanwhile, last month the state of Wisconsin, where patients get transplants relatively quickly, sued HHS, trying to stop the regulations in federal court. Louisiana has filed a similar suit.

Some observers see no quick end to a battle that has engendered consider- able lobbying on Capitol Hill and bitterness among transplant centers.

“I’d like to believe people are sick of this issue,” said Dr. John Lake of the University of Minnesota, president of the American Society of Transplantation. “But the factions seem to have their loins girded and are ready to do battle.”

Pennsylvania Offers Organ Donor Incentives

By Hope Yen - Associated Press Writer

HARRISBURG, Pa. (AP 3/30/00) Pennsylvania is modifying a novel plan to offer $300 to the families of organ donors, saying the money can only cover incidental costs such as food, housing and transportation.

A governor’s advisory committee last fall recommended offering the money for funeral costs in hopes of encouraging organ donations, because demand for transplants is surging.

But amid concerns the plan amounted to an illegal cash payment for organs, Health Secretary Robert Zimmerman said he was modifying the program to cover only incidental costs.

“I try to look at this in terms of the end rather than the means,” Zimmerman told members of the advisory committee Wednesday. “The end is to promote and support and provide benefits to people who make difficult decisions.”

A 1984 federal law prohibits payments or other considerations for organs and tissue. The law exempts “reasonable payments” for incidental costs associated with recovering and transporting the organ, but it does not specifically mention funeral expenses.

Pennsylvania’s three-year pilot program, the first of its kind in the nation, could begin as early as September after the advisory committee works out details.

Many states, including New York and Hawaii, have said they will be watching to see if it is worth pursuing on their own.

Some members of the Pennsylvania advisory committee said the program’s attempts to comply with laws against organ buying made it confusing. And other skeptics wondered whether the modest payment offer would increase donations.

“It’s probably legal but it doesn’t make a lot of sense,” said George Annas, who writes on health law for the New England Journal of Medicine.

“I can’t imagine that throwing in transportation costs would make a difference.”

For Failing Hearts, Doctors Synchronize Ventricles

By Thomas M. Burton - Staff Reporter of The Wall Street Journal

Cincinnati (3/15/00)The prognosis for most people with congestive heart failure is bleak, and Tom Brauninger was no exception. He gasped for breath. He could barely walk. Doctors put him on the waiting list for a heart transplant.

Most such patients don’t survive to get a transplant. Mr. Brauninger never got one. But there’s a twist: He now bicycles 10 miles daily, plays tennis and seems downright spry for 65.

Whether his recovery is a fluke or the result of a new treatment is a question of keen importance in cardiac medicine.

If it’s a fluke, it is one of many. In Europe and Canada, where the new treatment was first tested, turnarounds such as Mr. Brauninger’s have been reported by the dozen. In the U.S., where clinical trials are now under way, success stories are starting to mount. “This goes beyond anything we’ve seen in heart-failure treatment,” says William T. Abraham, director of the heart-failure program at the University of Cincinnati Hospital, one site of the U.S. trials.

The new treatment involves a device that electronically synchronizes the beating of the right and left ventricles, the heart’s pumping chambers. This corrects a problem that many of those with the chronic condition known as heart failure face: out-of-sync beating that leaves blood sloshing back and forth uselessly inside the heart. The resynchronization device prompts the ventricles to pump nearly simultaneously, as they should, sending blood into arteries and on through the body.

As an alternative to a heart transplant, it is almost absurdly simple. Doctors can install the devices on an outpatient basis.

So far, the technology has received little attention. But three U.S. companies Medtronic Inc., Guidant Corp. and St. Jude Medical Inc. are racing to win regulatory approval for a resynchronization device. Minneapolis-based Medtronic, which calls its device InSync, and Indianapolis-based Guidant, with a device it calls Contak, are furthest along, having already won approval to offer the technology in Europe and hoping for U.S. approval in 2001.

Today, at a meeting of the American College of Cardiology in Anaheim, Calif., Medtronic plans to make public the results of trials it did in Europe and Canada.

Clinical testing of the devices is far from complete, and their early promise could turn out to be deceptive. The largest completed trial of InSync involved only 103 patients in Canada and Europe and had no control group; that is, patients given nonfunctioning devices.

Control groups tend to expose placebo effects. That’s important because “patients with heart failure, provided with something new and exciting, respond like anyone to something new and exciting,” cautions Milton Packer, chief of the heartfailure unit at New York Presbyterian Hospital. “When we take patients and shower them with attention, they tend to respond.”

The history of treatment for heart failure-the condition in which the heart can no longer pump sufficient food to feed other organs is replete with examples of therapies that initially looked promising, only to fail in more rigoro studies. Even so, Dr. Packer says, “the potential is that this will work.”

Besides its completed foreign studies, Medtronic is conducting U.S. clinical trials at Cincinnati and 34 other medical centers. All of the eventual 375 test subjects will have the device implanted, but to form a control group, half of the devices will be switched off for several months.

Guidant is enrolling patients for an even larger study, more than 2,000 patients, to test its device. Some heart-failure patients have blockages in their hearts’ electrical systems that disturb the heart rhythm. Until the companies’ U.S. trials are completed, it won’t be possible to know precisely which patients’ electrical-conductivity problems can be successfully treated with these devices.

Some physicians involved in the trials believe that 25% to 50% of heart-failure patients could benefit. If so, that would make the resynchronization device one of the biggest developments ever in heart- failure treatment. The inadequacy of existing treatment is seen in mortality data: Half of the five million Americans afflicted with heart failure die within five years of diagnosis. The condition is the leading U.S. cause of hospitalization for people over 65, contributing to three million emergency- room visits yearly. And as modern technology enables more people to survive various cardiac illnesses, more end up with heart failure.

At the moment, the main treatment is pharmaceutical. Diuretics and other drugs known as ACE inhibitors and beta blockers help some patients regain enough strength and breathing power to rise out of bed. And better drugs are on the way. But the small European/Canadian study of Medtronic’s InSync found significant improvements in heart-failure patients’ health after treatment with the device for one month, six months and one year. The improvements continued over time.

Dr. Abraham says they were 2 1/2 to four times the improvements achieved with the leading drugs. “This means the difference,” he says, “between patients spending most of their time in bed or in a chair, out of breath or fatigued, and on the other hand being ambulatory, leaving the home and performing daily activities like going shopping.”

Of course, the most celebrated treatment for heart failure is the heart transplant, success at which has brought fame and riches to some skilled surgeons and medical centers. But fewer than 3,000 human hearts a year become available for transplant in the U.S., prompting scientists and cardiologists to search endlessly for a workable alternative among animal and mechanical hearts. Some of these options have failed utterly, while others still hold promise. Meanwhile, a majority of the 50,000 or so U.S. heart-failure patients who could be helped by a transplant don’t qualify, for age or medical reasons, or die while waiting for one.

And a heart transplant is a mixed blessing even for those who get one. The procedure is ghastly, like any open-chest surgery, requiring use of a bone saw to slice the rib cage. After hours in surgery, the patient faces a lengthy period, often a lifetime, of taking dozens of pills daily. Many are immune suppressors, to prevent organ rejection, and leave the patient always susceptible to infection.

Little wonder that Doug Spencer seized the offer of an alternative. “It sounded horrible, getting cut open and having somebody else’s heart put in, 60 pills a day for the rest of your life,” says the retired construc4ion worker. Dr. Abraham found that Mr. Spencer belonged in that subset of heart- failure patients who had the electrical- conductivity problem for which the devices are designed. A year ago, Mr. Spencer had Medtronic’s InSync put in.

In the surgery, the device, little bigger than a quarter, is placed just under the skin in the shoulder area. The patient typically is conscious, though sedated. The operation, though considered minor, can take from one to several hours, because the surgeon must thread wires down into the heart. Following surgery, the patient continues taking drugs indefinitely, though nothing like the regimen of transplant patients.

Before Mr. Spencer had the procedure, the 70-year-old could barely walk the few feet to his mailbox. Afterward, “within a month, I started feeling better,” he says.

Now he bowls as many as six games at a time. Recently he took his grandchildren to the King’s Island amusement park near Cincinnati for 14 hours. “I think the kids were tireder than me,” he says.

The idea of resynchronizing the pumping chambers dates to the early l970s. A cardiologist and researcher named Morton Mower was testing an implant- able defibrillator, designed to electrically jolt a racing or chaotically beating heart back to the proper rhythm. During this work, Dr. Mower noticed that some heart-failure patients had abnormal cardiac electrical activity.

It occurred to him that heart failure, too, might be treatable electrically. Working in the l980s at Eli Lilly & Co.’s medical-device business which in the early 1 990s became an independent company, Guidant he toyed with resynchronization devices without telling senior executives, who were skeptical.

By the early l990s, he had enlisted doctors in the Netherlands and the U.S. to start implanting early versions of what became Guidant’s Contak. The results persuaded management to get behind the idea. European trials began in 1995. Guidant’s European study, smaller than Medtronic’s in Europe and Canada, found that the amount of time heart-failure patients had to spend in the hospital each year fell to five days from a usual 26 days or so.

Around the same time, a Medtronic engineer heard about a young French cardiologist, Daniel Gras, who had begun hooking up old-fashioned pacemakers to heart-failure patients’ ventricles. (Pacemakers use small electrical impulses to speed up slow heartbeats.) One patient was so sick he couldn’t get out of bed, but a homemade electrical device had “a kind of magic effect,” says Dr. Gras. Within three days, the man could climb several flights of stairs.

The Medtronic engineer persuaded his superiors to get behind the idea, and soon the company was working with Dr. Gras in developing what would become InSync. The sharp improvements found in the European! Canadian Medtronic study continued for at least a year. And in the U.S. trials, now a year old, improvements also seem to be lasting, researchers say. The University of Cincinnati is about to take a third InSync recipient off the heart- transplant list.

Florida Eyes Death Row Organ Donors Lawmaker Wants ‘Something Good’

From Executions

By Scott A. Pignone

Tallahassee, Fla. (APBnews 3/28/00) - Inmates executed by lethal injection in Florida someday may be able to donate their organs for transplant under a proposal by a state legislator who says the plan would allow some good to come of executions.

Rep. Bill Andrews, R-Delray Beach, introduced the bill in the state House of Representatives last month, not long after Florida changed its method of execution. Electrocution destroys internal organs, but lethal injection leaves them available for transplant. “The idea for this bill came from a surgeon friend of mine that suggested we try to make something good come out of the executions,” Andrews told APBnews.com. “Some people have the horrible image of a murderer that can do no good in their mind, and we have to look at them with a different perspective.”

Florida currently has 368 inmates on its death row in state prison in Starke.

Kill the brain, save the body
House Bill 999, An Act Relating to Anatomical Gifts by Capital Defendants, would give inmates a new choice for execution, although the drugs that might make it possible are not yet available. A drug would be administered that would stop all brain functioning, while the cardiopulmonary system would continue to work until organ recipients could be found.

Currently, lethal injection stops the condemned person’s heart, and organs can be harvested immediately after death.

“I’m just running the idea up the flagpole for now,” Andrews said. “We need to consider these possibilities with our current growing inmate population and look to them as an untapped resource for these types of procedures.” More than 2,300 people are waiting for organ transplants in Florida and 68,000 others nationwide, according to LifeLink, a Florida organ transplant network.

High-risk population for disease
However, organ transplant organizations apparently don’t feel that inmates provide a suitable donor base for transplants. All five of Florida’s licensed organ transplant organizations are on record opposing Andrew’s bill.

“One reason why we are opposed to this bill is that inmates are categorized by the Centers for Disease Control as ‘high-risk’ for diseases such as AIDS and hepatitis,” said Ruth Bell, LifeLink’s vice president for public relations.

“Another reason for our opposition is that there is currently no scientific method to induce the ‘brain death’ that is described in the bill.”

The U.S. Food and Drug Administration prohibits the transplant of any tissue or organ from inmates, because of the possibility of disease, according to officials.
Additionally, Bell said regular execution methods would result in organs unsuitable for transplant.

Secondary motives alleged
Andrews said he takes exceptions to the criticism of the organ organizations. “There’s been some misrepresentation from the organ networks regarding this issue. I have some doctor friends within those networks that say this idea can work,” Andrews told APBnews.com. “I think there’s some secondary motives going on with the transplant organizations.

“You can even use parts of the body, such as the cornea, muscles and skin, even if it’s been subjected to the drugs of lethal injection,” he added.

Florida, like other states that have adopted lethal injection, currently uses a three-drug process. Sodium pentothal puts the inmate to sleep, pancuronium bromide stops breathing and potassium chloride stops the heart, according to the Florida Department of Corrections.

Additionally, Andrews said he is going to amend the bill to include a provision that the Department of Corrections offer organ donation cards to imates inmates as they are processed into the system.

The bill is in committee.

Contributed by Tx Dave Cannavo

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