Researchers say they have developed a novel drug that can prevent irregular heartbeats that lead to sudden cardiac arrest, which kills hundreds of thousands of Americans each year. 

The drug, which hasn't been tested yet in people, seals off a leak in a crucial channel that provides calcium to the heart muscle between each beat. Deprived of sufficient calcium, the heart can beat erratically, possibly leading to a fatal stoppage.

According to a study being published today in the journal Science, 10 mice bred to have a leak in the pathway and given the treatment thrived without developing any abnormal heartbeats while eight of nine untreated mice died after suffering irregular heartbeats, known as arrhythmias.

"We've shown that by fixing the leak in this channel, we can have a dramatic improvement in the outcome of this disease," said Andrew Marks, director of the Center for Molecular Cardiology at Columbia University Medical Center, New York, and leader of the study.

Enormous challenges remain before such a medicine could reach the market. Only a tiny percentage of compounds tested in animal studies ever prove safe and effective enough to become marketable drugs. But the findings open up a whole new avenue for treating heart failure and preventing irregular heartbeats.

The version of the drug used in the mouse study is being developed by the pharmaceuticals unit of Japan Tobacco Inc. Dr. Marks said he and his colleagues have fashioned a new but similar drug that is more potent and less toxic, and it has been successfully tested in other animal studies. The hope is that human tests can begin within two years.

Neither drug is similar to the calcium channel blockers already on the market to treat blood pressure, he said.

If a leak-sealing drug proves safe and effective, it could potentially help the more than 4.5 million Americans who suffer from congestive heart failure, a chronic and progressive weakening of the heart that leaves people short of breath and debilitated. They are six to nine times more likely than the general population to die of sudden cardiac arrest, according to the American Heart Association. The same defect underlies the rare, but often highly publicized, incidents when athletes collapse and die without warning due to an inherited heart disorder.

Dr. Marks said that both heart-failure patients and people with the genetic defect develop a leak in the channel that supplies the heart with the calcium -- the fuel necessary for the contractions that pump blood to the body. Normally, the channel opens to provide a dose of calcium just as the heart contracts and then closes completely to replenish and get ready for the next beat. But in patients with heart failure, the channel doesn't close properly, so calcium leaks out between beats. "When the signal comes for the channel to open," he said, "there isn't enough calcium for a strong muscle contraction."

The result is a gradually weakening heart and conditions that promote arrhythmias that disrupt the heart's electrical properties. That creates a climate for sudden cardiac arrest.

The drug restores the ability of the channel to close when the heart muscle relaxes without actually blocking the channel, Dr. Marks said. That is a key effect since most drugs that act on channels block them entirely, an effect that would be detrimental in this case.

"The work is very detailed, very complete and very convincing," said Elizabeth Nabel, scientific director for clinical research at the National Heart Lung and Blood Institute, a division of the National Institutes of Health that helped fund the research.