Pretorius’ coronary bypass research boosted by grant
Performed more than 400,000 times a year in the United States alone, coronary artery bypass grafting (CABG) is one of the most common surgical procedures in this country. Though the procedure has been perfected over the past four decades it’s been in use, excessive bleeding can be a serious consequence of the cardiopulmonary bypass required for surgeons to work on a stilled heart. In fact, as much as 20 percent of the nation’s blood transfusions are associated with CABG surgeries.
Investigating the cause of this perioperative bleeding is the focus of a grant received recently by Dr. Mias Pretorius, assistant professor of Anesthesiology at Vanderbilt. The Research Career Development Award, funded by the Department of Veterans Affairs, provides three years of both salary and research support to clinicians just entering a research career. Pretorius’ proposed studies hold the promise of leading to novel strategies for reducing bleeding and the requirements for blood products during CABG procedures.
Control of blood coagulation comes from a fine balance of clotting and anti-clotting factors in constant circulation within the bloodstream. Two such factors are at the crux of Pretorius’ work: bradykinin, which dilates and increases permeability of blood vessels, and tissue plasminogen activator (t-PA), which is integral to clot prevention.
Levels of t-PA increase following cardiopulmonary bypass, leading to increased fibrinolysis (breakdown of the fibrin proteins that make up clots) and bleeding. Preliminary data from Pretorius’ laboratory have led to two hypotheses: that bradykinin stimulates t-PA release during the bypass procedure, and that pharmacologic agents or genetic factors that influence bradykinin degradation or receptor function may alter t-PA formation.
“Basically, what I’m trying to do is look at factors that influence fibrinolysis during coronary bypass,” Pretorius said. “I’ll be looking at the effect of ACE inhibitors, drugs widely used in patients with coronary artery disease, as well as genetic factors that may influence (bleeding) during bypass.”
Pretorius came to Vanderbilt in 1996 after earning his medical degree from the University of Pretoria in South Africa. He followed a residency in anesthesiology with a fellowship in cardiothoracic anesthesia. At that same time, he joined the inaugural class in the Master of Science in Clinical Investigation program, with Dr. Nancy J. Brown, associate professor of Medicine and Pharmacology, serving as his graduate advisor. Pretorius completed that degree program last spring.
Brown will also mentor Pretorius in the work funded by this new award, as will Dr. Jeffrey R. Balser, James Tayloe Gwathmey Professor of Anesthesiology and Pharmacology, and Dr. Douglas E. Vaughan, C. Sidney Burwell Professor of Medicine. The award is slated to start in April of this year.