Time-Released Capsule Delivers "Growth Factor" To Improve Coronary Bypass Surgery

Bypass surgery -- where veins or arteries from another part of the body are grafted alongside the blocked vessel -- usually improves blood flow to the heart by bypassing the damaged portion of the artery. However, in some patients whose heart disease is widespread, or where the affected artery is very small, the bypass procedure is often unable to restore blood flow to the heart.

Researchers wanted to learn whether the growth factor therapy, designed to promote the growth of new blood vessels to replace the blocked ones, was safe for heart patients.

Researchers injected the basic fibroblast growth factor into heart patients who were undergoing bypass surgery and had areas of the heart where blood flow could not be completely re-established. The growth factor leads to a process called angiogenesis, which promotes the growth of new blood vessels in the heart.

Other techniques have been used to grow new blood vessels. However, this study was different because it used a protein, not a gene, was a double-blind, randomized controlled study and was done on bypass patients.

"Patients receiving the highest dose of the growth factor showed an improvement in blood supply and heart function, while the patients receiving much lower doses of the growth factor or those not receiving the treatment, had no increase in blood flow or heart function," says Michael Simons, M.D., associate professor of medicine at Harvard Medical School and director of the Angiogenesis Research Center, Beth Israel Deaconess Medical Center, Boston.

The growth factor was placed in time-released capsules coated with heparin, and then surgically placed in the fatty tissue near the blocked vessel during bypass surgery. The capsule allowed the growth factor to be released over a four to six week period.

The 24 patients in the study were unable to undergo a complete bypass procedure, and, therefore, a portion of their heart was left without adequate oxygen. Researchers inserted 10 capsules containing the growth factor along the artery that could not be grafted. The patients were divided into three groups: Eight patients received 100 micrograms of growth factor, eight received 10 micrograms of growth factor, and eight received a placebo or "dummy" pill containing no growth factor.

To determine the success of the growth factor therapy, researchers assessed the patient's level of chest pain (angina). Chest pain following bypass surgery is often an indication that blood flow to the heart has not been fully restored. All of the patients receiving the highest dose of growth factor were free of chest pain. One of the patients in the lower dose growth factor group experienced chest pain as did three of the eight patients in the control group.

Nuclear stress testing three months after the surgery showed a worsening in the blood flow of the control group. There was no significant change in blood flow in the 10 microgram group. However, those in the high dose growth factor group showed improvement in blood flow. Also, the area of the heart without adequate blood flow, which averaged around 19 percent prior to the growth factor therapy, decreased to about 9 percent.

In addition, magnetic resonance imaging (MRI) showed a reduction in the size of the area in the heart without proper blood flow from about 15.7 percent to 3.7 percent in patients treated with 100 micrograms of growth factor.

Researchers add that there was no evidence of any adverse side effects from the growth therapy treatment.

"While the number of patients is small, we clearly saw an effect with the 100 microgram treatment group," says Simons. "This study showed that the growth factor therapy could be done safely and is a viable strategy for treating heart disease."

Simons says a larger study of the growth factor therapy involving 120 patients is currently underway.

Co-authors are Roger J. Laharn, M.D.; Frank W. Selke, M.D.; Elazer R. Edelman, M.D., Ph.D.; Justin D. Pearlman, M.D., Ph.D.; Anthony Ware, M.D.; David L. Brown, M.D.; and Jeffrey P. Gold, M.D.