Marrow injection gets damaged hearts moving

November 17, 2002

CHICAGO, Nov. 17 - In one of the first studies of its kind, researchers discovered that bone marrow cells injected directly into the heart significantly enhanced function, according to findings reported today at the American Heart Association's Scientific Sessions 2002.

Heart wall contraction improved significantly after patients had their own bone marrow injected into scar tissue caused by heart attacks. Heart wall motion improved within weeks of treatment and persisted for at least 10 months after treatment in 14 patients.

"The benefit (of transplanting bone marrow into scar tissue of the heart) could be seen only six weeks after injection," says Manuel Galinanes, M.D., a heart surgeon at the University of Leicester in the United Kingdom.

The technique is a new way to strengthen heart muscle after a heart attack, he adds.

Bone marrow has been used for years to treat certain types of cancer and disorders affecting the body's disease-fighting immune system. Marrow transplantation is an attractive therapy because it can form healthy new cells. Bone marrow also has the potential to develop into many different types of cells.

"Bone marrow not only can differentiate into heart cells, but also smooth muscle cells, connective tissue cells and other types of cells to reconstitute the entire structure of a tissue," Galinanes says.

The investigators have yet to prove that bone marrow creates a new cellular infrastructure in heart scar tissue, but "that is the only possible explanation," Galinanes says.

The British team treated patients whose hearts had been severely damaged by heart attacks. All patients had low ejection fractions, meaning the heart muscle had lost much of its ability to pump blood into the circulation. The bone marrow injections were given during non-emergency coronary artery bypass surgery. Before surgery, each patient had a stress test to confirm abnormal movement in the walls of the heart muscle. The test involved injecting dobutamine, a drug that simulates the effects of exercise on the heart, including a faster heart rate, higher blood pressure and more forceful contractions. Heart function, including wall motion, was evaluated by echocardiography, an imaging test that uses sound waves to generate pictures of the beating heart.

Bone marrow for the treatments was obtained from the patient's sternum (breast bone). The marrow was diluted in a small amount of the patient's own blood, then injected directly into scar tissue identified during the heart surgery.

"We confirmed the scarring on the heart muscle before and during surgery," Galinanes says. "The ability to confirm the presence of scar tissue with dobutamine stress echo before surgery, and then confirm it again during surgery, told us that the affected area was dysfunctional and the abnormality was irreversible. We wanted to make sure that we were injecting the marrow into dead tissue to help ensure that the injection would not pose any serious risk to the patient."

Dobutamine stress echocardiography was repeated six weeks after surgery and again at 10 months. The researchers looked at the effect of the bone marrow on heart wall motion in the immediate vicinity of the scar (regional) and in the left ventricle (global), the heart's primary pumping chamber. The regional wall motion score decreased significantly from an average of 2.41 prior to injection to 2.16 after six weeks and 2.09 after 10 months. A lower score means less movement abnormality. The global wall motion score also decreased significantly from 1.96 before surgery to 1.64 at six weeks. It remained largely unchanged at 1.65 after 10 months.

The researchers plan to study the effects of bone marrow injection in more patients who have scar tissue and impaired heart function after heart attacks. They've begun laboratory experiments to find out how the bone marrow cells change the scar tissue and improve heart function.

The initial study was limited to patients undergoing bypass surgery, but bone marrow cells could be delivered to the heart through a much smaller incision or possibly by non-surgical injection. If more studies continue to show that the procedure is safe and improves heart function, the researchers might begin to consider other ways to implant the cells, Galinanes says.

If bone marrow injection successfully restores heart function after heart attacks, the treatment would be a welcome addition to other competing strategies, such as gene therapy, growth factor therapy and laser treatments, he says.
Co-authors are Mahmoud Loubani; Joan Davies, Ph.D.; Derek Chin, M.B.; John Pasi, Ph.D.; and Peter Bell, M.D.

Abstract 2292
This abstract will be included in a news conference on cell transplants.

American Heart Association

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