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Scientists Search for Cause of Sudden Death

Researchers Use Pigs to Examine How the Brain Influences Functioning of the Heart

By Haibin Jiu

In trying to understand how psychological stress causes death from a heart attack, researchers at the Harvard School of Public Health (SPH) are studying the physiological reactions of pigs to non-painful stress.

"Our research can be categorized as neurophysiology or biopsychology," said Debra A. Kirby, lecturer in physiology at the SPH, "as it combines both the psychological component and the biological component [of the body system]."

"We are interested in how the responses of the brain can alter the electrical activity in the heart," she continued, pointing out that such activity can be fatal, even if the victim has never had any heart problem.

"The human counterpoint to this [external stimulus] is how your psychological response affects how the heart functions," she said.

Sudden Deaths

Each year about 400,000 people in the U.S. die of sudden cardiac death. Kirby said most of these deaths are suspected of being caused by ventricular fibrillation, the most fatal form of irregular heart rhythm, or arrhythmia.

"Many of those people already have heart diseases of some kind, but many do not," said Kirby. While only 20 percent of the deaths occur among people under the age 65 and five percent to people under 45, young people are affected by the type of stress that proves fatal.

According to Kirby--who heads the cardiovascular laboratory at the SPH--arrhythmia sometimes results from stress. How the abnormal response of the heart is started is not understood by researchers yet, she said.

"There is evidence, and we believe, that response in the brain to stimuli can trigger this," Kirby said, while emphasizing that the exact mechanism behind the fatal attack is not well known.

"Many physicians can tell you that a patient who has stressful experiences often has heart problems," Kirby said.

In the research conducted by Kirby and her co-workers, which involves animal rather than human subjects, they are trying to find out how stress hormones, such as the neural hormone norepinephrine, released from nerve endings in response to certain stimuli, affect the functioning of the heart.

"The hormones are neurally active," she said. "They are chemicals that affect the entire body system. They are released both in the brain and heart and the nervous system."

"When it's important to respond to challenges," she adds, "your brain releases chemicals that cause the nerves to be activated. They work together. But sometimes some things don't work properly."

Scientists in this country and all over the world are working hard to explain the link between stress and heart failure. But, Kirby said, the research is hard to carry out and yields few conclusive results because experiments are conducted on animals, not humans.

"You can't put a person in stress [artificially]," said Kirby.

Animal Models

Another important aspect of the research done by the SPH team is that they "study only non-painful types of stress," Kirby said. "This is because people who are under stress are usually frustrated, not in pain. We try to model this as best as we can in animals."

The experimenters do this by putting a group of pigs under non-painful stress--by such techniques as lifting their feet several inches off the ground--and comparing the levels of norepinephrine in these pigs to the levels of the hormone in a control group of non-stressed pigs.

The pigs were chosen because their hearts "are similar to those of humans," Kirby said. Models of the pigs' physiological response to stress have shown that the animals under stress have higher levels of norepinephrine than their counterparts in control groups. The pigs subjected to stress even develop ventricular fibrillation.

"We think this shows that stress can make arrythmia easier to induce," Kirby said.

One of the goals of the study, Kirby said, is to find ways to "predict why only some people develop fatal heart rhythms under stress." Such an understanding will not only help prevent sudden stress-caused deaths but will facilitate the discovery of drugs to aid the heart in times of frustration, she said.

The research is funded by the Lown Cardiovascular Research Foundation, a non-profit private organization founded by Bernard Lown, professor of cardiology in nutrition at the SPH, said Arlene Fortunato, director of the foundation.

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