Heart of the matter.

• Author: March, Keith L.
• Position: Neighborhood Heart Watch - Daniel Meldrum researches heart disease at Indiana Center for Vascular Biology and Medicine

Unlocking the mystery of cardiovascular disease is the focus of intense research across the globe. Despite amazing advances, heart disease remains the number-one cause of death in the United States.

In his busy research laboratory at Indiana Center for Vascular Biology and Medicine (ICVBM), cardiac surgeon Daniel Meldrum and his team are trying to uncover the underlying mechanisms at work in heart disease, zeroing in on the action of one particular protein called tumor necrosis factor (TNF). An inflammatory protein, TNF is elevated after acute episodes--heart attack, stent placement, heart transplant--and during chronic heart diseases, such as congestive heart failure. Researchers believe that TNF may be a major culprit in the progression of heart failure.

By determining the role of TNF, Dr. Meldrum eventually hopes to develop novel drugs to block the production of the protein during ischemic conditions such as heart attacks and heart surgery, thereby helping to treat heart failure. To learn more about TNF and his promising research into organs for transplant, NHW spoke with Dr. Meldrum, an assistant professor in the departments of surgery and physiology at Indiana University School of Medicine and an ICVBM investigator.

NHW: What is the focus of your research at ICVBM?

DM: Basically, we are looking at ways to protect the heart during what is referred to as ischemia reperfusion injury, or reduced blood flow to the heart. Conditions that cause no or low blood flow to the heart include heart attacks, heart surgery, heart transplantation, and trauma--such as from an automobile accident that causes severe hemorrhage. Since heart disease is the leading cause of death among both men and women, this is an important area of research.

My research specifically focuses on how TNF is produced by the heart, and on developing ways to inhibit its production. TNF is a key component that injures the heart during heart attacks and heart surgery.

To better identify the mechanisms at work, we are investigating human tissue during heart surgery. With internal review board (IRB) approval, we are studying the function of portions of the heart discarded during surgery. If successful at identifying the mechanisms at work, we may be able to produce a drug more specific for human TNF production in acute low-blood states.

Low blood flow occurs and causes damage in other organs as well, and we are comparing the pathways of TNF-mediated injury in the kidney, heart...