Reversing "Hibernating" Heart Muscle Focus of UB Researchers

BUFFALO, N.Y. -- Heart researchers at the University at Buffalo have received a $2.5 million five-year grant to develop new strategies to reverse a heart dysfunction called "hibernating myocardium" that can cause disabling heart failure and sudden death.

Hibernating myocardium is a condition in which myocytes (cells in the heart's muscular tissue) shut down, but remain viable in areas that receive reduced blood flow over an extended period of time due to narrowed arteries. This creates areas of the heart that contract poorly.

The new grant from the National Heart Lung and Blood Institute builds on pioneering work of scientists in UB's Center for Research in Cardiovascular Medicine who developed a novel pig model with hibernating myocardium.

Previous research has shown that, while restoring blood flow to these "hibernating" regions improves function and a patient's prognosis, cells in the left ventricle (the heart's main pumping chamber) often remain chronically dysfunctional and do not return to normal. The reasons for this remain unclear, researchers say, but in most circumstances do not appear to be caused by replacement with scar tissue.

The new grant will allow researchers to determine if the metabolic changes that myocytes undergo in order to remain viable during hibernation limit their long-term ability to recover fully after revascularization.

John M. Canty, M.D., Albert and Elizabeth Rekate Chair in Cardiovascular Disease in the UB School of Medicine and Biomedical Sciences and chief of the Division of Cardiovascular Medicine, is principal investigator on the grant. Canty is a head of the Cardiovascular Disease Group of the New York State Center of Excellence in Bioinformatics and Life Sciences at UB.

The researchers will undertake concurrent physiological, proteomic and mitochondrial functional studies in the swine model that will be translatable to humans. Proteomic profiling will identify candidate mitochondrial proteins in the swine with established viable dysfunctional myocardium that do not have significant cardiac scar tissue.

"These protein studies will be coupled with assays of mitochondrial respiration and of the activity of specific enzymes in the swine model," said Canty. "This work relies on the state-of-the art proteomic research facilities and mass spectrometry at UB.

"By using therapies similar to those that are used clinically in patients, such as angioplasty and adenoviral gene transfer to over-express growth factors in the heart, we can identify how changes in the molecular pathways responsible for the adaptation to decreased blood flow can be reversed more completely. The ultimate goal of manipulating these pathways will be to restore full contractile function."

Areas of hibernating myocardium are common in patients with heart failure arising from coronary artery disease, Canty noted. "Determining how this impacts prognosis is the focus of the UB Cardiovascular Center's PAREPET (Prediction of Arrhythmic Events with Positron Emission Tomography) clinical trial, which also is funded by NHLBI.

"Identifying the basic mechanisms responsible for incomplete functional recovery after revascularization hopefully will lead to new therapies that will improve the outlook and symptoms of these patients who are at high risk for adverse cardiovascular events," said Canty.

Additional investigators on the study are Alan D. Hutson, Ph.D., professor and chair of the UB Department of Biostatistics; Te-Chung Lee, Ph.D., associate professor of biochemistry; Jun Qu, Ph.D., research assistant professor of pharmaceutics, and Michael D. Banas, M.D., research assistant professor of medicine.

Kenneth Blumenthal, Ph.D., professor and chair of the UB Department of Biochemistry, and Robert Straubinger, Ph.D., associate professor of pharmaceutics, will serve as study consultants.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. The university is in full compliance with mandates of state and federal regulatory agencies pertaining to the humane use and care of research animals.