Contact: Frank Hoke

Heart Cells Closely Control Their Own Oxygen Supply

Cardiac contractile cells - the cells that power the heartbeat - actively protect themselves from levels of oxygen in their own blood supply that are either too high or too low, according to a new study. The cells secrete substances into the surrounding fluid that diffuse to the vessels serving the heart and trigger them to constrict or dilate as needed to closely control the amount of oxygen-rich blood reaching the cells. The results stem from a collaborative project involving researchers at the University of Pennsylvania Medical Center and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France.

The findings suggest that one of the mechanisms of injury involved in atherosclerosis and other cardiovascular diseases may be the disruption of this finely tuned system of biochemical crosstalk between heart cells and the vessels supplying them with their needs.

"This is a system that controls the coronary blood vessels so that the amount of blood flow to the heart is just right," says Saul Winegrad, MD, a professor of physiology and lead author on the study, which appears in the October 15 issue of Circulation Research. "If this mechanism is impaired for any reason, damage to the heart can result. Inadequate blood flow will quickly cause injury, while excessive blood flow will likely cause problems in the long term."

The fact that heart cells, also known as myocytes, seek to avoid low levels of oxygen due to inadequate blood flow is not surprising - doctors have long known that cardiac ischemia quickly results in a heart attack. But the current study is the first to show that myocytes also will not tolerate high levels of oxygen associated with excessive blood flow.

"What is wrong with having more blood reach the heart than is needed?" asks Winegrad. "The answer is that too much blood means too much oxygen, which can lead to the formation of free radicals, highly reactive molecules now commonly invoked as contributors to heart disease, cancer, and other chronic disorders."

The optimal oxygen concentration in the blood reaching myocytes is about 6 percent, the study reveals, and the permissible window is quite narrow - only about 1 percent up or down from the optimal figure. As oxygen levels rise above 6 percent, the heart cells release increasing amounts of a substance called angiotensin I, which is converted to angiotensin II by the cells in the walls of the blood vessels. The angiotensin II, then, stimulates the vessels to constrict. When oxygen levels fall below 6 percent, the cells secrete adenosine, which acts directly to trigger dilation of the vessels. (For comparison, oxygen concentration in the air is about 20 percent, substantially higher than the oxygen concentration in the blood supplying the needs of myocytes. It is lower at the surface of the cardiac cells because they are using the oxygen.)

To demonstrate the system's activity and identify its components, the researchers first isolated individual cardiac contractile cells and exposed them to different concentrations of oxygen. They then collected the fluid surrounding the cells and introduced it into isolated blood vessels. When the oxygen concentration was above what the scientists later found to be optimal, the blood vessels rapidly constricted. When it was below the optimal level, the vessels dilated. Further laboratory analysis allowed the investigators to identify the active substances being secreted into the surrounding fluid by the cells in the presence of different oxygen concentrations and their targets in the blood vessels.

In addition to Winegrad, the other authors on the study are Daniel Henrion, PhD, INSERM U 141, Lydie Rappaport, PhD, INSERM U 127, and Jane Lise Samuel, MD, PhD, INSERM U 127, all associated with H"¢pital Lariboisi"¢re, Paris. The research was supported by a Fogarty Senior International Fellowship for Winegrad and grants from the American Heart Association and the INSERM.

The University of Pennsylvania Medical Center's sponsored research and training ranks second in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation - $201 million in federal fiscal year 1998. In addition, the institution continued to maintain the largest absolute growth in funding for research and training among all 125 medical schools in the country since 1991. News releases from the University of Pennsylvania Medical Center are available to reporters by direct e-mail, fax, or U.S. mail, upon request. They are also posted electronically to the medical center's home page ( and to the electronic news service Newswise (


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