Computer Models Of The Heart Can Help Cure Cardiac Ills

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July 25, 1997FOR IMMEDIATE RELEASECONTACT: Phil Sneidermanprs@jhu.edu

COMPUTER MODELS OF THE HEART CAN HELP CURE CARDIAC ILLS

The dog heart on Raimond Winslow's computer screen is beatingerratically.

The diagnosis is severe arrhythmia, abnormal electrical activitythat could kill the dog within minutes. Winslow gave the dog thismalady by manipulating the numbers that created its heart -- athree-dimensional model that exists only inside the computer.Now, he changes a few numbers again, this time to adjust themicroscopic gates or ion channels that regulate electrical excitability incardiac cells. Moments later, the heart is beating in a slower, more regular fashion. For this computer-animated organ, "death" is no longer imminent.

Human hearts can also benefit from this high-tech marriagebetween biology and computer technology, says Winslow, anassociate professor of biomedical engineering at The JohnsHopkins University. Using a highly detailed computer model thatmimics the way a heart works -- down to the sub-cellular level -- hestudies serious cardiac disorders and mathematically "tests" thedrugs that might cure them.

He begins by translating the heart's physiological functions intonumeric formulas, using the latest data collected by biologists.Then, by making small changes in the model, he can see howcertain enzymes, proteins and other molecules make the heart beatproperly -- or improperly.

Using this model, Winslow is looking for medicines that couldprolong the lives of millions of people suffering from congestiveheart failure. His experiments have already shown that certaindrugs used to control high blood pressure might also preventsudden cardiac death.

Winslow and his key research partner, Denis Noble, have formed acompany, Physiome Sciences Inc., to pursue commercialapplications of this software and to market drug leads discoveredby the team.

Noble, a professor at England's University of Oxford, developedthe first mathematical models of electrical activity in the heartmore than 30 years ago. By building on Noble's work and creatingeven more elaborate computer models, Winslow believes the team isbreaking important new ground. "Before our project," he says, "noone had ever simulated electrical arrhythmias in athree-dimensional model of the heart and then used it as avehicle for testing drug actions."

In recent months, Winslow has discussed this research before TheInternational Union of The Physiological Society in St.Petersburg, Russia, and at a conference on Computational Biologyof the Heart in San Diego. His current model replicates a dogheart, which functions much like a human one. But Winslow says,"The methodology will also work with other organ systems andtissues."

This technique -- using numerical models to study biologicalfunctions -- dates back to the early 1950s, when two Britishscientists used crude hand-cranking calculators to come up withmathematical equations representing the electrical activity of asquid's nerve. Today, advances on two scientific fronts have madethis area of research even more fruitful. First, biologists arecollecting far more detailed information about how cells, andeven genes, interact to determine a person's health. At the sametime, computer technology is much more powerful and accessible,making it easier for researchers to compile and manipulate thesecomplex findings.

"There's just an explosion of cellular and molecular data on theproperties of heart tissue," Winslow says. "In a sense, themodels have not kept pace with this explosion of data, andthere's a real need to create ever more biophysically detailedmodels of individual heart cells that incorporate all of thisinformation."

By using such computer models of the heart, Winslow says,pharmaceutical companies will be able to dramatically narrowtheir searches for life-saving medicines--and save millions ofdollars now spent on conventional trial-and-error methods. "Ifyou can tell a company to search for a drug that has a specificeffect on a particular ion channel," he says, "that's important,because once these companies know what kind of drug to look for,they have the technology to screen more than 10,000 compounds aday in an effort to find such a drug."

This technique could also lead to breakthroughs involving otherorgans. "Models are tools for discovering the functions ofbiological mechanisms," Winslow says. "The approach can be usedbeyond just the heart. It could be applied to other diseases,other biological systems. We're using the heart as a firstexample, sort of a jumping-off point."

Some of Winslow's computer simulations of electrical activity inthe heart can be found at the following World Wide Web address: http://www.bme.jhu.edu/~rwinslow

This research is supported by grants from the National Science Foundation and the Whitaker Foundation.

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