Heart May Be Able To Repair Damage
By David Brown
Washington Post Staff Writer
Thursday, June 7, 2001; Page A01
New research has revealed that heart muscle regenerates to some extent after a heart attack -- a finding that contradicts the prevailing view and suggests a new strategy for treating the country's leading cause of death.
A team of Italian and American researchers reported yesterday that it had detected clear evidence that after a heart attack, muscle cells in the region of damaged tissue divide and grow for many days. A smaller number of cells farther away are also dividing, it says.
The finding moves the heart into the rapidly expanding club of organs that appear to have a capacity for self-repair. It raises the possibility that researchers might be able to find substances that could be injected into the heart after a heart attack to amplify regeneration already underway.
"The dictum has always been, as we are rushing to treat [a heart attack], that once lost, heart tissue is lost forever," said Todd K. Rosengart of Northwestern University, who was not involved in the study. "There's now evidence that we may be able to reclaim heart muscle, and that completely changes everything we have thought about heart disease."
Based on the new findings, the researchers are already trying to identify growth factors or stimulants capable of turning up cell division in the heart. They envision a procedure in which such substances could be injected into the border zone around dying heart tissue, using a catheter threaded into the heart chambers through a blood vessel.
Heart tissue has a complex architecture that includes blood vessels and connective tissue, as well as muscle cells. Stimulating muscle growth alone may not restore heart function.
Research in animals, however, suggests that muscle cells transplanted into a damaged heart also stimulate blood vessel growth, if they take, said John Fakunding, director of the heart research program at the NIH's National Heart, Lung and Blood Institute.
Numerous research groups in the United States and Europe are experimenting with ways to augment heart function without surgery. These include injecting specific genes, or relatively primitive cells taken from the bone marrow, into oxygen-starved heart tissue in the hope they will stimulate the growth of blood vessels.
A study published two years ago by the same group of researchers presented evidence of heart muscle regrowth, but was generally disbelieved. The new findings are more dramatic and likely to be more convincing.
"My main purpose is to force people to change the paradigm and go after the regenerative capacity, because if you could direct this regeneration to the dead tissue we could repair the damage," said Piero Anversa, a physician at New York Medical College whose study appears in today's issue of the New England Journal of Medicine.
In a heart attack, a clot forms in an artery feeding a region of heart muscle, depriving the tissue of oxygen and nutrients. If blood flow is not restored within about 12 hours, the tissue dies and is eventually absorbed by the body and replaced with scar tissue.
Anversa and his colleagues studied hearts from 13 people who died four to 12 days after having a heart attack. The researchers compared the hearts to those of 10 people who died of other causes (mostly trauma). The researchers stained the heart tissue of both groups with a chemical that illuminates dividing cells.
In a band of tissue bordering the area of heart muscle killed by the heart attack, there were 84 times as many cells undergoing division as in the tissue of the people who had died of other causes. Even in a band of tissue far away from the dead area, there was increased cell division -- about 28 times as many dividing cells as in the controls.
The researchers checked their findings using a second method of identifying dividing cells. The results were roughly the same: 70 times as many dividing cells in the border zone, 24 times as many in the distant one. In all, about 4 percent of muscle cells adjacent to the damaged area were dividing.
The study Anversa and his colleagues published two years ago found evidence that hearts of people with severe congestive heart failure -- a condition in which the heart is enlarged and contracts poorly -- also contain dividing cells. However, the number of dividing cells is much higher in the heart attack group.
The study only looked at the appearance of the cells, not their function. There is no direct evidence they work or are properly incorporated into the functioning heart.
Numerous other organs -- including the skin, liver and blood -- have an innate capacity to replace complicated structures and populations of cells under some circumstances. Recent research even suggests that the brain contains cells that can divide and become mature neurons. The common course of many diseases, however, is clear evidence that self-repair isn't up to the task required.
"It's possible that for low-level damage, this regenerative capacity in these adult organs can restore some tissue," speculated Ron McKay, a neuroscientist at the National Institutes of Health. "But when the damage is major -- when you have a stroke in the brain, or a heart attack in the heart -- the function isn't restored adequately."
An unanswered question in the new research is whether the dividing cells reside in the heart, or are summoned in from elsewhere after a heart attack. Anversa says his team has preliminary evidence it's the former. |
