New Approach to Protect Heart Tissue After Cardiac Arrest: Experts

by Tanya Thomas on Jul 15 2008 8:54 AM

In a major breakthrough in the study of heart disease and tissue damage, experts at The Children's Hospital of Philadelphia claim they have devised a way to manipulate cell activity that occurs during the interruption of blood flow. This will strongly protect the heart tissue from irreparable damage, which would occur otherwise.

The researchers revealed that they made this advance while experimenting on mice.

According to them, their approach has the potential to become an emergency treatment for heart attack patients, particularly since already existing drugs might be pressed into service to produce the protective effects.

"Reduced blood flow, or ischemia, is a major problem in many organs, where it can lead to cell death and tissue damage. We decided to look for a global approach to protecting heart tissue by inhibiting enzymes that govern how cells respond to ischemia," said study leader Dr. Peter J. Gruber, a cardiothoracic surgeon at Children's Hospital and a faculty member of the University of Pennsylvania School of Medicine.

The researchers say that their study built on a previous study by other researchers that showed that drugs called histone deactylase (HDAC) inhibitors reduce ischemic injury in the brain.

They say that they used the HDAC inhibitors in mice with induced heart damage.

"We found significant and dramatic results in the mice. The HDAC inhibitors reduced the area of tissue injury, even when delivered an hour after the ischemic event occurred," said Gruber.

The treatment was found to reduce the size of the myocardial infarction-an area of dead tissue caused by obstructed blood flow, as occurs after a heart attack-by more than half.

When Gruber and his colleagues set out to determine how the HDAC inhibitors acted, they found that these inhibitors blocked gene pathways that led to cell death and ischemia-induced vascular permeability, the leakage of fluid through blood vessels.

The researchers say that their study also suggested that a specific molecule called HDAC4 was the likely enzyme with the most critical role in affecting how cells respond to ischemia.

Gruber says that one of reasons why they are so excited about their findings is that a number of HDAC inhibitors are already used in medicine for treating both cancer and epilepsy, and are well tolerated.

He concedes that much research remains to be done.

The researcher, however, insists that the new findings raise the possibility that existing drugs, or their modified versions, may play an important new role in heart disease.

Gruber also reckons that therapies base don his research may lead to an emergency treatment following a heart attack because the protective effect of HDAC inhibitors may occur even after the initial blockage of blood flow.

He further says that such treatments may also protect tissues from the adverse effects of interrupting blood flow during open-heart surgery for both children and adults, which requires a period in which the heart is stopped.

Gruber says that the next step for his team will be to test how HDAC inhibitors work in protecting against ischemic injury in larger animals.

An article on the study has been published in the journal of the Federation of American Societies for Experimental Biology (FASEB).