Novel approach may protect against heart attack injury

July 10, 2008

Researchers at The Children's Hospital of Philadelphia have manipulated cell activity that occurs during the interruption of blood flow to strongly protect heart tissue in animal studies. The finding 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," said study leader Peter J. Gruber, M.D., Ph.D., a cardiothoracic surgeon at Children's Hospital and a faculty member of the University of Pennsylvania School of Medicine. "We decided to look for a global approach to protecting heart tissue by inhibiting enzymes that govern how cells respond to ischemia."

Gruber's team published their findings online July 7 in the journal of the Federation of American Societies for Experimental Biology (FASEB). The article will appear in the journal's October 2008 print issue.

The researchers made use of drugs called histone deactylase (HDAC) inhibitors that alter the way DNA is packaged within cells, as well as modifying the function of other proteins. Building on previous work by other researchers, who showed that HDAC inhibitors reduce ischemic injury in the brain, they used the same agents in mice with induced heart damage.

"We found significant and dramatic results in the mice," said Gruber. "The HDAC inhibitors reduced the area of tissue injury, even when delivered an hour after the ischemic event occurred." The size of the myocardial infarction--an area of dead tissue caused by obstructed blood flow, as occurs after a heart attack--was reduced by more than half.

In further investigating how the HDAC inhibitors acted, Gruber's team found they blocked gene pathways that led to cell death and ischemia-induced vascular permeability, the leakage of fluid through blood vessels. They also identified a specific molecule, HDAC4, as the likely HDAC enzyme with the most critical role in affecting how cells respond to ischemia.

An important advantage of their finding, said Gruber, is that a number of HDAC inhibitors are already used in medicine, for treating both cancer and epilepsy, and are well-tolerated. Although much research remains to be done, he added, this raises the possibility that existing drugs, or modified versions of them, might play an important new role in heart disease.

Because the protective effect of HDAC inhibitors may occur even after the initial blockage of blood flow, therapies based on Gruber's research may lead to an emergency treatment following a heart attack. In addition, because open-heart surgery for both children and adults requires a period in which the heart is stopped, such treatment might also protect tissues from the adverse effects of interrupting blood flow during surgery.

For now, said Gruber, the next step for his study team will be to test how HDAC inhibitors work in protecting against ischemic injury in larger animals.
-end-
A National Institutes of Health grant partially supported the research, in addition to funding from the McCabe Foundation, the University Research Foundation and the Division of Pediatric Cardiothoracic Surgery at The Children's Hospital of Philadelphia.

Gruber's co-authors were Anne Granger, Ibrahim Abdullah, Faith Huebner, and Thomas Huebner, of Children's Hospital; and Jonathan A. Epstein, M.D., of the University of Pennsylvania School of Medicine. Gruber, Granger, and co-authors Andrea Stout and Tao Wang are members of the Penn Cardiovascular Institute, of which Epstein is the scientific director.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

Children's Hospital of Philadelphia

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.