Mechanisms of Sudden Death
Scientists in the Center for Research in Cardiovascular Medicine at the University at Buffalo have received $1.85 million from the National Heart, Lung and Blood Institute to study the role of abnormal cardiac sympathetic nerve function in sudden cardiac death.
Sudden cardiac death results from a catastrophic disruption in heart rhythm. Each year it claims the lives of more than 350,000 seemingly healthy men and women in the U.S., yet physicians continue to be perplexed about its underlying mechanisms.
Earlier research by UB cardiologists using an animal model of coronary heart disease showed that sympathetic nerve dysfunction, which occurs in heart attacks, also can develop in regions of the heart that are still alive, but not working normally. These regions of "hibernating myocardium" develop in parts of the heart that are supplied by narrowed blood vessels.
These investigators have shown that animals with areas of hibernating myocardium are at high risk of arrhythmias, leading to fibrillation and sudden death. They suspect that the regional differences in sympathetic nerve activity between normally functioning and hibernating myocardium increases this risk.
The new research, led by James Fallavollita, M.D., UB associate professor of medicine, will investigate four scenarios involving this difference in nerve activity within the heart. Activity will be measured using a special isotope that is taken up by nerve cells and imaged with positron emission tomography. The first three projects make use of UB's unique pig model of hibernating myocardium, while the fourth involves patients undergoing coronary artery bypass grafting.
The first project will test whether the sympathetic nerve dysfunction associated with hibernating myocardium can be reversed by opening up the blocked artery and restoring normal blood flow.
The second project will determine whether the abnormalities in sympathetic nerves are different in research animals that die of sudden death compared to those that survive. This phase also will study whether new nerve growth, which would result in hyperstimulation in parts of the heart muscle, is related to sudden cardiac death.
The third project will test whether destroying all of the sympathetic nerves in the heart prevents sudden death. Fallavollita hypothesizes that if there are no sympathetic nerves, there can be no difference between regions, and without difference there would be no fibrillation or sudden death. Heart cells have the capacity to keep the heart beating without sympathetic nerves, Fallavollita notes, eventhough the nerves provide an extra boost in a fight-or-flight situation.
The fourth project, which will be conducted in patients undergoing coronary artery bypass surgery, is similar to the first project. The scientists will determine whether normalizing blood flow in patients will improve sympathetic nerve function and if so, how much improvement will occur and over what time frame. In addition, they will use small biopsies of the heart obtained at the time of surgery to identify tissue characteristics that determine which patients show improvement.
Additional investigators on the four-year grant are Michael Haka, Ph.D., clinical associate professor of nuclear medicine and Arturo Valverde, M.D., assistant professor of medicine.
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.