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The Heart - More than Just Brawny Muscle

Lovers know that the heart is a mysterious organ, but solving the mystery of what the heart does was a matter of life and death for doctors.

News Release 2009-30 ]

At a Glance

Who - Adolfo de Bold is a professor of pathology and laboratory medicine at the University of Ottawa Heart Institute.

Issue - Researchers suspected the heart had some mysterious endocrine function, but no one had studied the issue in depth.

Solution - De Bold discovered Atrial Natriuretic Factor (ANF), a hormone that regulates how hard the heart has to pump by communicating with the kidneys to control salt concentrations in the body.

Impact - The discovery of the heart's endocrine function literally rewrote the medical textbooks. It offered doctors a new way of easing the load on stressed hearts and provided a blood test to diagnose heart failure and assess the efficacy of its treatment.

Your heart is a tireless workhorse, pumping thousands of litres of blood every day of your life. And, for many years this was thought to be its only function, until Dr. Adolfo de Bold, a professor of pathology and laboratory medicine at the University of Ottawa Heart Institute, discovered that the heart did much more.

In 1969, when de Bold came to Canada from Argentina to do his MSc and PhD, he begged to work on a dormant research project of his supervisor's, the study of the then unknown function of the heart's muscle cells. Of specific interest was a feature found within these muscle cells, storage granules that looked very similar to the ones that produce insulin in the pancreas.

His training in Argentina had been on a related topic, and he recalls he had "a big desire to discover something, although I didn't know at the time how much of a chance I was taking."

De Bold toiled away in isolation in the labs, but he began to understand that these granules did indeed release a hormone that de Bold named Atrial Natriuretic Factor (ANF) that controlled water and salt levels in the body. In essence, when the heart muscles were stressed they would release ANF which then told the kidneys to filter out salts and reduce the amount of fluids the overworked heart had to pump.

When he injected the substance into rats, it had a major impact causing them to excrete a very large amount of urine. Next he isolated and sequenced the peptide hormone that was causing the effect and named it Atrial Natriuretic Factor (ANF).

Once his work was published, it excited what has been called "a revolution in our thinking... and a blizzard of papers that together educated a generation of investigators." The discovery of ANF showed for the first time this new function of the heart muscle, which could allow doctors to either increase or decrease the load on the heart, an essential process for reducing hypertension and helping the heart compensate after heart failure.

As well, measuring ANF levels in the blood is a widely-used diagnostic test that doctors can use to assess heart health. "It's a very precise measure of the health of the heart," said de Bold. "As I frequently say, if the levels of this hormone are normal in the blood then nothing is wrong with your heart."

Looking back, de Bold realizes just how lucky he was to be able to study what he wanted on his own, although his solitary research did present a huge challenge when it came to finding the necessary equipment and funding to keep the project running.

"I have many stories of how we were at the brink of losing everything at the very beginning," said de Bold. "We were lucky to run into some provincial funding to buy the protein sequencer which was just shear chance. The research that I witnessed myself doing has been heavily reliant on divine providence and serendipity."

Despite his major discovery, de Bold is still studying this mysterious protein and its many effects. He's found that ANF has effects even beyond what he originally imagined, guiding molecules in and out of cells on a pathway.

"It's a huge impact, this discovery of new systems and new cellular signals," said de Bold. "There are many things that are really just beginning with this finding. It's kind of like insulin, we still don't know the whole story about it, so it's a lot to be done still."