Probing New Ways to Reduce Damage from Heart Attack, Stroke

Feb. 14, 2010
Paul Brookes, Ph.D.

Two Rochester scientists are among the authors of a Nature Biotechnology paper that explores new ways to screen for drugs that might be useful for a range of conditions, including cardiovascular problems like heart attack and stroke.

Graduate student Andrew Wojtovich and Paul Brookes, Ph.D., associate professor of Anesthesiology and of Pharmacology and Physiology at the University of Rochester Medical Center, are part of a team of scientists that is looking at how cells convert nutrients into energy.

The team, led by Vamsi Mootha, M.D., of Massachusetts General Hospital, studied the ability of nearly 3,700 compounds to shift cellular energy metabolism in a precise way, by altering the processes involved in cellular energy production – glycolysis and respiration. Scientists believe that prodding cells to shift from one process to the other in a precise, controlled way may offer a new way to fight diseases like cancer as well as heart disease and stroke.

The team identified a handful of drugs, including eight approved by the U.S. Food and Drug Administration, which can shift cellular energy metabolism in a subtle way that might be useful for treating disease. The results were published online Feb. 14 in Nature Biotechnology.

In work supported by the American Diabetes Association and the Smith Family Foundation, the team took an especially close look at meclizine, a drug used to treat nausea and vertigo, by using a model of heart attack damage developed by Brookes’ team in Rochester. Experiments in rats showed that pretreatment with meclizine dramatically reduced ischemic damage in both isolated cells and intact perfused hearts, after simulated heart attack; the medication also reduced damage to brain cells after stroke.

While the results suggest that treatment with drugs like meclizine may someday be useful for reducing the damage associated with heart attack or stroke, Mootha stresses that much additional study is needed. “Before we can think about human studies, we need to do rigorous animal testing to determine optimal, safe dosing regimens and learn more about how this drug works,” he said.

Added Brooks: “An editorial last year highlighted the fact that there are currently no FDA-approved drugs for the lowering of myocardial infarct size in humans. Thus, further screens such as this one have the potential to initiate new research in that direction.”

The work is part of a growing number of studies exploring the possibility of reducing damage from a heart attack or stroke by somehow prepping tissue, perhaps by giving those at high risk of having a heart attack or stroke a medication that would lessen the damage if such an event occurs.

For nearly 25 years, scientists have been investigating “ischemic preconditioning,” a technique where briefly cutting off and then restoring blood flow to arteries prior to a heart attack protects against the tissue damage that results from the heart attack. Brookes’ group is among the laboratories investigating the phenomenon. A little more than a year ago his team discovered that a molecule known as nitro-linoleic acid or LNO2 is involved in the process.