DURHAM, N.C. - It's a cruel irony that the body's most
crucial components are also the most vulnerable. Snap your
spine and you're paralyzed because nerve cells can't
regenerate. Damage your heart muscle in a heart attack and it
can't mend itself.

"You are born with all the heart cells you'll ever have,"
says Duke molecular biologist and heart researcher Doris
Taylor. "Once you damage the heart muscle, it's gone forever.
The heart can't regenerate new muscle."

Yet as any bodybuilder knows, if you strain your biceps
pumping iron they respond by building new muscle. In a
deceptively simple idea, Taylor decided to try to recruit the
services of individual skeletal muscle cells to actually
regenerate dead heart muscle.
"Skeletal muscles, the muscles we use to get around, get
damaged all the time when we strain them by overuse," Taylor
said. "The skeletal muscles have specialized cells called
myoblasts that can reproduce to fix damaged muscles."

Taylor reasoned that she might be able to recruit myoblasts
taken from a tiny plug of a patient's arm or leg muscle to
boost the contraction of a failing heart.

"Right now treatment options to prevent progression to heart
failure after a severe heart attack are severely limited,"
Taylor said.

During a heart attack clogged arteries in the heart
suffocate the heart muscle, depriving it of oxygen and
nutrients long enough to kill muscle that keeps the heart
pumping. When enough heart muscle is damaged, it can no longer
pump efficiently. The remaining heart muscle cells grow larger
to compensate, but that only makes the heart more inefficient.
The result is congestive heart failure, a chronic condition
that kills more than 41,000 annually in the United States and
Europe.

For severe heart failure, heart surgeons can implant a
mechanical pump that assists the heart until a suitable donor
heart can be found for transplantation. A new experimental
procedure, called cardiomyoplasty, uses skeletal muscles taken
from a patient's back or abdomen to wrap around an ailing
heart. The muscle is stimulated by a device similar to a
pacemaker to augment weak heart muscle. But, Taylor said, the
skeletal muscle isn't really hooked up to the heart; it acts
more like a mechanical assist device.

"Our idea is similar to earlier experiments by researchers
at other universities who are trying to implant fetal muscle
cells into hearts to stimulate growth," Taylor said. But, she
added, that idea is not practical because there is no ready
supply of fetal tissue and it could cause an immune reaction.
The advantage of using muscle cells from each patient is that
it is their own tissue, which won't be rejected by the immune
system.

She is testing her idea using rabbits, which have hearts
very similar to human hearts. Unlike some animals, rabbits have
heart attacks just like people, Taylor said.

Her early studies, published in the May 1997 issue of the
Proceedings of the Association of American Physicians, show
that it is possible to isolate myoblasts from arm or leg
muscle, grow them in a laboratory dish for a few days and then
inject them into the heart where they take up residence in the
existing heart muscle.

In that study, Taylor and cardiologists William Kraus and
Brian Annex, heart surgeons Dr. R. Eric Lilly, Dr. Scott
Silvestry and Dr. Donald Glower, all of Duke, and pathologist
Dr. Sanford Bishop of the University of Alabama at Birmingham,
tried two ways of getting myoblasts into the heart. They
injected the cells directly into the heart muscle using a
needle and syringe, and found that in using this method, the
myoblasts took up residence in an area around the injection
site. And they learned that if they injected too much fluid,
the heart rhythm became unstable and the rabbits died. In a
second method they used a catheter, similar to those used to
clear blocked arteries in balloon angioplasty, to infuse the
cells into the heart. In this experiment the cells became much
more broadly distributed across the damaged section of heart
and integrated into the heart muscle.

Based on these findings, Taylor and her collaborators are
now studying how well the introduced cells work to boost
contraction.
"Usually, if 30 to 40 percent of the left ventricle is damaged
it can lead to congestive heart failure," Taylor said. "We
found we can deliver 10 million cells, enough to replace up to
75 percent of the damaged tissue."

New research, done in conjunction with surgeon Zane Atkins
and a team of medical students, will test how well the cells
actually work to boost contraction.

Preliminary findings suggest the cells are indeed
contracting in otherwise dead tissue and improve the function
of the heart, Taylor said. Since myoblasts are skeletal muscle,
which by its nature contracts when stretched, Taylor explained,
the cells likely respond by contracting when they are stretched
as the heart's chambers fill with blood. But it is too soon to
say precisely how much they are contracting, she added.
Investigators at other institutions are trying similar
strategies by implanting genetically engineered animal cells
into damaged hearts, but Taylor said she believes her group can
accomplish the same goal without using cells from animals or
cells that have been engineered.

"We think we can use skeletal muscle and get nature to do
the engineering for us," Taylor said. "I like the idea of
treating patients using their own cells."

However, Taylor also plans to combine her work with findings
reported in February by Dr. Thomas-Joseph Stegmann, and his
colleagues of Fulda Medical Center, in Fulda, Germany. These
researchers were able to induce damaged heart muscle to
regenerate new blood vessels using a human growth factor called
fibroblast growth factor 1 (FGF 1) that they produced with
genetic engineering techniques.

"If we could combine new blood vessel formation with new
muscle formation, we could for the first time, regenerate
living heart muscle where there was only dead tissue," said
Taylor.