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Team targets sudden cardiac death
By LOIS BAKER
Contributing Editor
Sudden cardiac death is a catastrophic disruption of the heart rhythm that can cause a seemingly healthy human to drop dead without warning.
More people die from sudden cardiac death (SCD) each year than from AIDS, breast cancer and lung cancer combined. The condition accounts for nearly 60 percent of all cardiovascular-related deaths, claiming the lives of approximately 300,000 people per year in the U.S.
Yet, because there are few warning signs or symptoms to identify people at risk, and since SCD is by definition fatal, leaving no survivors to study, scientists know little about the underlying mechanisms that cause the condition.
Researchers at the new Center for Research in Cardiovascular Medicine at UB are poised to change that scenario. Aided by a $1.5 million grant from the John R. Oishei Foundation, the university has assembled a cadre of specialists in several fields who are investigating SCD from the single-cell-level up, with the goal of developing strategies for treatment and prevention.
"Great strides have been made in treating ischemic heart disease, heart attack and heart failure," said John M. Canty, Jr., director of the center. "However, the impact of these developments on sudden cardiac death is disappointing.
"The percentage of sudden deaths is increasing, while mortality from other cardiovascular causes continues to decline. As a result, sudden death has become one of the nation's major public health problems," added Canty, holder of the Albert and Elizabeth Rekate Chair in Cardiovascular Disease in the School of Medicine and Biomedical Sciences.
A multidisciplinary team encompassing specialists in cardiology, physiology, biophysics, biochemistry, genetics, pharmacology and toxicology, positron emission tomography (PET) scanning and electrophysiology already is at work on this perplexing problem, bringing more than $16 million in active biomedical research funding in related disciplines to bear on the question.
They are interested particularly in studying a phenomenon called "hibernating myocardium." In this condition, heart cells receiving a reduced blood supply due to arterial narrowing adapt to a life-threatening situation by reducing their function and oxygen needs. This survival technique allows cells to remain viable and able to resume normal activity when and if surgery restores full blood flow.
Nevertheless, since areas of hibernating myocardium exist side-by-side with normal heart muscle, the disparity in electrical activity can result in rhythmic chaos, making the heart vulnerable to fatal arrhythmias.
"Although much previous research has focused on the role of scarring following a heart attack as the underlying factor leading to the arrhythmias responsible for sudden death," said Canty, "we think that the areas that are viable and hibernating may actually be a greater risk factor."
The researchers have circumvented the problem of having few human survivors to study by creating the hibernating myocardium phenomenon in the first animal model—a pig—for the disease, and implanting a defibrillator similar to that used in patients with advanced heart disease. When an arrhythmia that ordinarily would be fatal occurs, the defibrillator activates, saving the animal and providing a living model of the sudden cardiac death syndrome to study.
By monitoring what transpires in the heart cells leading up to a potentially fatal ventricular fibrillation and analyzing the physical and biological changes in the heart post-SCD, the researchers can gain information never before available.
"Once an aborted sudden death episode occurs," said Canty, "we can study the heart physiologically, as well as identify transient cellular and molecular changes that may be going on at the time of an arrhythmia."
One of the major projects the center is undertaking involves comparing heart function in the animal model before and after the "sudden death episode" with heart function of patients with known coronary disease. In a parallel study, researchers will attempt to determine if the electrical problems seen in hibernating myocardium are caused by the presence or absence of receptors for neurotransmitters, such as norepinephrine, released during the activation of the sympathetic nerves controlling heart function.
The study will determine if the receptors have changed, or if they are responding abnormally to the neurotransmitters. It also will help determine whether sympathetic system abnormalities are caused by destruction of the nerves or malfunction, and will show whether normal nerve function returns after blood flow is restored.
In another major project, patients will undergo PET scanning before and after coronary bypass surgery to determine whether electrical activity to the heart can return to normal, which could explain favorable effects of surgery on reducing sudden death in some patients. PET scanning allows researchers to monitor biological processes noninvasively in real-time. Using this technology, researchers hope to identify changes early on that could lead to identifying patients at high risk of sudden cardiac death and develop routine diagnostic procedures to detect these changes and correct them.
Other projects concern the control of electrical activity within single heart cells and changes in significant peptides affecting vessel constriction in the SCD model and in patients. Data from these studies will feed into the most basic research component of the center: identifying which genes are expressed and which proteins are altered in the cascade of events that result in sudden cardiac death.
"Our goal is to identify the underlying biological triggers and warning signals of this disease process," said Canty. "When scientists know the condition's biological markers, they can identify people at risk and develop treatments to prevent it. We are hoping to make this happen."
Additional principal investigators in the center and their departments are James A. Fallavollita, medicine; Dennis Higgins, pharmacology and toxicology; Michael S. Haka, nuclear medicine, and Kenneth M. Blumenthal, chair, Te Chung Lee and Steve Toorongian, biochemistry.
Also, Harold Strauss, chair, Michael J. Morales, Randall L. Rasmusson, Gyula Szigeti and Shimin Wang, physiology and biophysics, and Norma Nowak, director of the UB-Roswell Park Cancer Institute microarray facility and director of scientific planning with the UB Center of Excellence in Bioinformatics.
The center is supported by grants from the Mae Stone Goode Trust, Albert and Elizabeth Rekate, and William H. Boardman and Jan Boardman endowments, and Medtronic, in addition to the Oishei Foundation. Individual center investigators are supported by the National Institutes of Health, the Department of Veterans Affairs, the American Heart Association and the National Science Foundation.