Spare parts for the new millennium
your blood thirsty heart
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Computer generated heart image courtesy Department of Engineering Science at the University of Auckland.





































 






































heart with I love bFGF t-shirt on it


























 



















Diagram of heart courtesy the American Heart Association.

a heart Bloodthirsty hearts
Although deaths are declining, heart disease remains a major killer of Americans. Heart disease, mainly caused by poor blood supply to the bloodthirsty muscles in the organic pump, is also a major cause of disability. According to the American Heart Association, in 1996, about 480,000 Americans died of coronary heart disease, and an equal number from other cardiovascular diseases.

Artery replacement is one answer to the problem of clogged arteries, and about half a million Americans get coronary artery bypass surgery each year. (Foggy about bypass surgery? The Why Files walks you through, stitch by stitch.) Even more get balloon angioplasty, which reams clogs from heart arteries without replacing them.

For many people, these operations are lifesavers. But too often, the repairs start to fail. Eventually -- sometimes in a year -- patients are again edging toward disability and sometimes death from heart failure.

Organic alternative
Instead of fixing heart arteries with tools, some scientists are trying to persuade the body to take a "do-it-yourself" approach. The identification of angiogenesis factors -- chemicals that cause blood vessels to grow -- raised the prospect of using chemicals to force heart muscle to grow new arteries.

Diligent Why Files readers know that blocking angiogenesis factors could help cure cancer. Here, we're talking about the flip side: using these potent chemicals to bring new blood to ailing hearts.

In supplying blood to the heart, more is better: Among bypass patients, higher blood supply is associated with less pain and better survival after five years. And angiogenesis factors did improve the blood supply in a new study (see "Local Perivascular..." in the bibliography). Michael Simons, Roger Laham, Justin Pearlman and other researchers at Harvard Medical School and Beth Israel Deaconess Hospital selected 24 people whose heart arteries were so poor that even bypass surgery would not restore blood to all the muscles. Pre and post treatment images of an MRI
Pre-Treatment:
A magnetic resonance image (MRI) of a patient with poor blood supply to the heart. Even with little activity, the patient had chest pain, despite taking up to 20 nitroglycerine pills daily. The image results from a special non-invasive technique developed by Justin Pearlman of Harvard Medical School. New vessel development would appear as a dark flare. The lack of a flare indicates that this patient has not developed necessary new vessels in the heart muscle.

Post-Treatment:
One month after treatment with growth factor, the MRI shows a dark flare indicating that a new blood vessel is branching from the larger vessel. The new vessel is above the arrow, where the blood supply was poorest. New vessels can improve the blood supply and relieve chest pain, as happened with this patient, who stopped taking nitroglycerine and resumed activity.

Both images courtesy Justin Pearlman

A little dab'll do ya
During bypass surgery, the doctors implanted pellets with an angiogenesis stimulator called basic fibroblast growth factor (bFGF) into heart muscle. The pellets were put in sick but living muscle, in places where new arteries could not be attached.

Without a new blood supply, this muscle was doomed.

The small trial was placebo-controlled and double-blind. The pellets contained 0, 10 or 100 micrograms of bFGF, but nobody know which pellets a particular patient got. After following the patients for an average of 18 months, the researchers opened the envelope telling them what pellets were used, and noticed that the group that got the highest dose:

    Had no angina (heart pain), while three of the eight placebo patients did.

    Showed signs of new blood flow on magnetic resonance images (MRIs).

    Had a reduction in the diseased heart muscle. The diseased area grew somewhat in the placebo group.

Bypassing the bypass
If bFGF is so helpful, why not use it to bypass bypass surgery, rather than in conjunction with surgery? It's a logical question (even if we weren't smart enough to think of it ourselves), and the idea might work. For example, if you block a pig's heart artery, it will grow some side arteries, or collaterals, but not enough to compensate for a full blockage. But if a pig is given a growth factor such as bFGF, "it forms such an extensive network of collaterals that you will not be able to tell that the artery is totally occluded," says Simons.

"This is natural bypass without surgery."

Simons and others are investigating how to use growth factors instead of surgery. Aside from reducing the need for expensive, dangerous surgery, it could conceivably lead to a more complete recovery.

But how to supply the drug? Angiogenesis factors have been implicated in cancer, and you don't really want your blood drenched with them. Anyway, if you pump bFGF into the blood stream, Simons says that less than .01 percent reaches the heart muscles. Pumping the chemical directly into the heart's arteries is not much more effective.

Getting wired
Simons and Pearlman are helping check out another technique -- using a catheter to squirt tiny amounts of growth factor directly into the heart muscle. Here's how it works (or would work -- since the whole procedure has only been tried on swine):

    You set up an electric field and a grid-shaped antenna under the patient, then feed a catheter with a magnetic tip through an artery into the heart. A magnet moving in an electric field makes electricity, allowing you to track the catheter with the antenna. A separate sensor detects electrical signals from living heart muscle, labelled diagram of heart helping distinguish it from dead. Since you want to get the angiogenesis factor into the margin between living and dead, this helps you target your injections.

    As you track the whole process on a computer screen, you move the catheter inside the heart and inject small amounts of growth factor where needed. Ideally, the technique could sidestep bypass surgery with a quick, relatively painless operation.

Angiogenesis research is still at an early stage, and Simons hopes to eventually use not a single chemical but a "master switch" chemical that stimulates several parts of the complicated angiogenesis process. His lab is testing one, called PR39, which, he says, "turns on multiple growth factor pathways."

But too much of a good thing may not be good at all, he admits. "You'd expect it to be a lot more potent, but it may be too broad, may attach to multiple cell types. Ideally you'd want to target just the single pathway you want, in just the cell type you want to change."

That's a fine dream, but as he admits, it's for the future. "We're not there yet."

Nor are we at the point of curing diabetes. But there's encouraging news on that front, too.


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