Gene Therapy Shows Promise in Protecting Hearts during Surgery

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CONTACT: Jennifer Holshouser

GENE THERAPY SHOWS PROMISE IN PROTECTING HEARTS DURING SURGERY

CHARLOTTESVILLE, Va., May 11 - During heart surgery, an estimated 5 percent of patients suffer damage to the heart muscle when blood flow is briefly cut off. But researchers at the University of Virginia Health Sciences Center have found that a method of gene therapy used in mice significantly protects the heart during periods of low blood flow.

In the study, published in this month's Journal of Molecular and Cellular Cardiology, the researchers examined the effects of genetically increasing the number of adenosine receptors on the surface of the heart. Adenosine is a chemical produced by the heart that regulates heart function and protects the heart during periods of low oxygen supply. Adenosine works through receptors on the heart muscle. "The receptors work a lot like light switches that require a key - adenosine - to turn on," said Dr. G. Paul Matherne, associate professor of pediatrics at U.Va. and principal investigator for the study. "We wanted to see if increasing the number of switches would result in greater protection for the heart."

To produce more receptors, Matherne's research team inserted a gene into the mice that caused them to have 1,000-fold more adenosine receptors than the control mice. They then isolated the hearts, stopped the blood flow and measured the recovery of function once blood flow resumed. - more - UNIVERSITY OF VIRGINIA - PAGE TWO "The data shows that increasing the number of adenosine receptors markedly improves the energy state of the heart when blood flow is stopped," Matherne said. "The energy levels were preserved by 10-fold or higher, and the overall recovery was 30 percent better than in normal hearts."

Matherne said that if scientists could develop a method for delivering the adenosine-receptor gene to the heart in humans, it would make the heart more tolerant to the stress of surgery. "During heart surgery, the heart must be put on a heart-lung machine and there's a brief period of time where blood flow to the heart is cut off," he said. "If we could replicate this genetic therapy in humans, we could better protect the heart during surgery."

Matherne has been studying the effects of increased adenosine receptors for more than three years and published a previous study that showed there were no detrimental effects of increasing adenosine receptors in mouse hearts. He recently received a four-year, $300,000 Established Investigator Grant from the American Heart Association to continue his research and expects to receive a grant from the National Institutes of Health later this spring.

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May 7, 1998

Dr. Paul Matherne can be reached at (804) 982-6020.