By Lisa Seachrist

Washington Editor

Blockages in the coronary arteries create regions in the heart that fail to get enough blood and are starved for oxygen. Left alone, a patient is likely to suffer a myocardial infarction as the oxygen-starved heart muscle fails to contract and dies.

Currently the most effective treatment for such blockages is coronary bypass surgery. However, using recombinant fibroblast growth factor (FGF-1), scientists from the Fulda Medical Center, in Germany, may have added a new tool to their treatment by creating new pathways to feed the oxygen-starved (ischemic) heart.

"FGF-1 induces the formation of de novo capillaries and vascular network in the region of the originally blocked blood vessels," said Thomas-Joseph Stegmann, head of thoracic and cardiovascular surgery at Fulda Medical Center. "The vessels improve heart function and prevent myocardial infarction. Our hope is to further develop this technique for the treatment of human coronary heart disease."

As a result of studies designed to understand how tumors recruit blood vessels in order to survive and grow, FGF-1 emerged as a likely candidate for such protein therapy because it is known to induce angiogenesis on its own and to stimulate the production of vascular endothelial growth factor (VEGF), which mediates the recruitment of smooth muscle cells to the walls of microvessels.

The German group studied the recombinant protein in rat hearts first. The animal studies showed that neoangiogenesis — the production of a new capillary network to bypass occluded blood vessels — occurred in the rat hearts by nine weeks after the researchers implanted tissue pretreated with the growth factor. Tissue implants treated with denatured growth factor failed to produce new capillaries.

Stegmann's group reported in today's issue of Circulation, dated Feb. 24, 1998, that in a randomized clinical trial, FGF-1 injection into the hearts of patients with coronary artery disease triggered a new network of capillaries that not only increased the blood flow to the ischemic heart, but improved heart function as well.

FGF-1 was used in 20 patients with multivessel coronary artery disease who had not undergone previous heart surgery. The patients received a bypass and were given an injection of FGF-1 in a dose of 0.01 milligrams per kilogram of body weight near the site of the bypass. Twenty control patients received the bypass operation and an injection of denatured FGF-1.

After 12 weeks, patients receiving FGF-1 had a significant new capillary network at the injection site as seen on angiography. And none of those new vessels had blockages. The control group failed to grow new capillaries.

Patient Follow-Ups Encouraging

A three year follow-up, which has yet to be published, indicates the FGF-1-treated patients are still enjoying benefits from their new capillary network. The ejection fractions — a measure of how much blood leaves the heart with each beat and an indication of how well the left ventricle is performing — for these patients improved from 50.3 percent to 68.8 percent. The control group experienced a smaller gain in ejection fraction due to the bypass operation, 51.5 percent to 59.4 percent.

"It means that growth factor FGF-1 is able to produce new vessels and capillaries in that area of the heart where we place the factor," Stegmann said. He also noted the procedure offers the most promise with diffuse coronary artery disease and atherosclerosis in the smaller vessels of the heart and the extremities.

Elizabeth Nabel, an American Heart Association board member and chief of cardiology at the University of Michigan, in Ann Arbor, said the results on recombinant protein therapy were encouraging for cardiovascular surgeons.

"This could be a very important therapy for a number of different patients suffering from coronary heart disease or small vessel disease," Nabel said. "The therapy could be used in patients with blocked coronary arteries who aren't candidates for bypass because they have medical problems; those with disease in many arteries where only some [arteries] can be treated with bypass; or, perhaps, in combination with a bypass."

Stegmann's group is working on developing a less invasive way of delivering the growth factor to the ischemic areas of the heart and other areas of the vascular system.

Nabel also pointed out that the German group treated the patients with a recombinant protein, and that in the future researchers will likely try gene therapy approaches.

"There is likely to be an exponential rise in the number of trials using growth factors to stimulate new blood vessel growth in the heart," Nabel said. *

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