Since the 17th century, when William Harvey discovered the circulation of the blood and compared it to a water bellows, medicine has thought of the human heart as a muscular pump.
New research is forcing scientists to rethink that notion. It also has profound implications for control of blood pressure and heart disease, and possibly for the artificial heart program.
Beginning with a stunning discovery by a Canadian researcher four years ago, scientists have learned that the heart secretes a powerful hormone that helps regulate blood pressure and the body's delicate balance of fluids and salts.
"This completely changes our concept of the heart as simply a pump," says John Lewicki, senior scientist at California Biotechnology Inc. (CalBio), a San Francisco Bay area genetic engineering company. "It makes the heart an endocrine organ, like the adrenal glands and the kidneys."
Endocrine organs help regulate the functions of other organs in the body by secreting hormones -- insulin, for example -- into the bloodstream.
The heart hormone has been dubbed auriculin because it is produced in the upper chambers of the heart, sometimes called auricles.
In animal experiments, auriculin has been shown to lower blood pressure by dilating the arteries. It also forces water and salt out of the body, which relieves strain on the heart. And it increases the efficiency of the kidneys.
No available drug combines those three functions as effectively as auriculin seems to, scientists say.
Discovery of the only known hormone in the heart has touched off a race by nearly 30 research teams in the United States, Canada and Japan to clone, synthesize, patent, test and market auriculin.
The stakes are high. Auriculin could lead to safer, more effective drug treatment for high blood pressure, congestive heart failure and kidney disease -- and to huge sales for the drug company that gets to market first.
An estimated 35 million Americans have hypertension, or high blood pressure, a leading cause of stroke. Last year, Americans spent more than $50 million on prescriptions for drugs that control hypertension alone.
Research teams from CalBio, Cornell, Vanderbilt and Japan simultaneously reported last June in the scientific journal Nature that they had isolated the gene that carries the code for auriculin, opening the way for production of large amounts of the hormone by genetic engineering.
Auriculin has "amazing action," says Dr. John Laragh, director of the Hypertension and Cardiovascular Center at New York Hospital-Cornell Medical Center.
"It's as powerful as the most powerful commercially available diuretic, and it also drops the blood pressure," Laragh says. "These two actions could mean it plays a major role in cardiovascular disease."
The findings have also profoundly changed science's view of the heart.
"We used to think of the heart as a rather dumb pump, which it is," says Laragh. "It just keeps on beating.
"But this discovery means the heart has a brain, with its own guidance system."
Working with CalBio genetic engineers, the Cornell researchers have produced large quantities of auriculin for extensive research on laboratory animals. They have applied for approval from the Food and Drug Administration for tests on humans, which Laragh says are "imminent."
Because auriculin is a natural substance produced in the human heart, he says, it is less likely to be toxic, in spite of its potency, than synthetic drugs now used to control blood pressure and regulate the body's fluid balance.
And since it seems to perform several functions at once, auriculin has the potential of replacing several types of drugs, including diuretics (which flush fluid from the body), natriuretics (which flush salt from the body) and vasodilators (which lower blood pressure by allowing the arteries to widen). Many of the blood pressure-controlling drugs that perform these three functions have undesirable side effects.
"This hormone embodies the properties, all in one molecule, of several synthetic diuretics and vasodilators," Laragh says.
The rapid pace of auriculin's development is "remarkable," says Dr. Floyd Rector, chief of the division of nephrology (kidney disease) at the University of California at San Francisco.
"Three years ago, no one believed it existed," Rector says. "Last year, three or four labs in the U.S. were producing it. This year, 12 or 15 labs are producing it. Next year, there will probably be 30."
Although no one knows for sure, Rector speculates that people with high blood pressure "either don't make enough of this stuff or are resistant to it."
Discovery of a natural hormone in the heart may also have implications for the artificial heart program. When William Schroeder, the world's second recipient of an artificial heart implant, suffered a stroke last December, his doctors were puzzled. The mechanical heart was working smoothly, pumping an adequate supply of blood through his body for the first time in years, but Schroeder gained 24 pounds in fluid soon after the operation and suffered other complications, including the stroke.
Dr. Paul Rosch, a Yonkers, N.Y., internist and president of the American Institute of Stress, offers a possible explanation: Schoeder's artificial heart makes a superb pump, but lacks the natural heart's ability to secrete hormones that help regulate the body's delicate balance of fluid.
"None of the explanations offered for this potentially dangerous complication," Rosch wrote in a letter to the editor of The New York Times, "seem to be as relevant as the observation that the human heart, in addition to being a pump, apparently also functions as an exquisite endocrine organ."
Citing reports of research on auriculin, Rosch concluded, "It should not be surprising that Mr. Schroeder's mechanical pump, deprived of such an apparently important homeostatic balancing safeguard, cannot fully reduplicate its human counterpart."
Neither Dr. William DeVries, Schroeder's heart surgeon, nor Dr. Robert Jarvik, president of Symbion Inc. and designer of the Jarvik-7 artificial heart, could be reached for comment. But Cornell's Laragh says Rosch's explanation sounds plausible.
"We never knew what would happen when you took the heart apart, until the artificial heart program," Laragh says. "Now we know.
"When the heart isn't there, you swell up. When they took his Schroeder's heart out, they took away his auriculin."
Although the atria or upper chambers of the natural heart remain intact in an artificial heart recipient, "whether or not they still have the ability to produce the hormone isn't clear," says CalBio's Lewicki. "It's an interesting possibility, but we just don't know."
Despite the unprecedented speed at which this hormone has proceeded from discovery to imminent clinical testing, auriculin is probably at least several years from commercial availability. Further testing, including detailed clinical trials on humans, are needed to determine all of its physiological actions and rule out untoward side effects.
Scientists say it is highly unlikely that the dramatic results in the animal tests will not be corroborated in tests on humans.
For auriculin to be effective in pill form, chemists also must find a way to protect it against digestion, which would chemically destroy it in the gut. Otherwise it would have to be injected or inhaled, which could limit its market.
But if those problems of drug delivery can be overcome and no unforeseen side effects are discovered, Lewicki says, "We're looking at a huge market."