Cardiovascular disease is the leading cause of death among Americans, and the most frequent reason for hospitalization in the VA health care system – and as such, it’s been a significant focus since the agency’s early years; the first VA cardiovascular research unit was established in 1935, at the Washington, D.C., VA hospital. In the 1960s, VA researchers provided the first definitive evidence that treatment for moderate high blood pressure could help to delay or prevent complications such as stroke or congestive heart failure.

“About 40 percent of the dollars we’re spending,” said Burgio, “are going toward basic research to understand what’s going on with cardiovascular diseases at the molecular and cellular level.”

VA cardiovascular research, aimed at improving the quality of life and patient care for veterans and their families, covers a broad spectrum, including the basic biological science behind the risk factors and pathological processes associated with heart failure; in vitro, animal model, and clinical trials of new treatments and therapies; and establishing or improving treatment methods and protocols in the health care setting, particularly within the context of chronic interrelated disorders.

According to Dr. Michael Burgio, who manages the VA’s Biomedical Laboratory and Clinical Sciences cardiovascular research and development programs, VA researchers are currently engaged in 38 clinical sciences studies and 26 clinical trials, nine of which are large, multi-site trials of particular medications or treatments. More than half – 155 – of the 307 cardiovascular research projects funded for 2015 were biomedical laboratory studies of the basic processes behind heart disease and related conditions.

“About 40 percent of the dollars we’re spending,” said Burgio, “are going toward basic research to understand what’s going on with cardiovascular diseases at the molecular and cellular level.” Such studies are difficult and complex, he said, but their share of VA’s cardiovascular research budget reflects their importance: “If we’re going to come up with innovative new ways to try to intervene and create new therapies, we really have to understand what’s happening in both the normal heart and the diseased heart, or in the normal and diseased vasculature, at this really fundamental level.”

 

Studying the Diseased Heart

The basics of heart attack are well known: When blood flow to the heart muscle is slowed or stopped, those cells are not getting oxygen, and they’re dying. What happens after an attack, when a medical team has established “reflow” of blood to the heart, is more mysterious: About 30 to 40 percent of heart cell death happens during this aftermath – and we still don’t understand why, but Dr. Ed Lesnefsky, chief of cardiology at the McGuire VA Medical Center (VAMC) in Richmond, Virginia, and professor of internal medicine at Virginia Commonwealth University, is leading studies that are shedding light on this phenomenon.

In animal models, Lesnefsky and his team have established that the mitochondria – the “powerhouses” – of oxygen-starved heart cells don’t function normally during reflow, producing harmful compounds and triggering mechanisms that result in cell death, rather than survival. “For example,” he said, “these mitochondria, instead of making ATP – making energy – divert their biochemical processes to produce bad things, one of which is, in laymen’s terms, bleach. So we’re interested in how these mitochondria can be modulated or biochemically manipulated to reduce cardiac injury during the reflow period, with the idea not only of preserving heart tissue, but also to minimize the transition to chronic heart failure states.”