A new, $2.8 million, four-year federal grant will support researchers at the University of Pittsburgh School of Medicine and their collaborators at Wake Forest University as they study why the quality of stored transfusion blood degrades over time and how to address the problem. This "storage lesion," as scientists call it, has been associated with increased risk for cardiovascular events and organ failure, particularly among compromised patients who receive multiple units of aged blood.
There is strong evidence that red blood cells lose some of their enzyme function and have a shortened life span during the time they are banked, explained co-principle investigator Mark Gladwin, M.D., director of the Vascular Medicine Institute at the University of Pittsburgh and chief of the division of pulmonary, allergy and critical care medicine at the School of Medicine.
"When the red cells hemolyze, or break apart, during storage, they leave behind micro-particle remains and the hemoglobin they contained," Dr. Gladwin said. "We suspect that after transfusion those remains lead to destruction of nitric oxide, which in turn can cause blood vessel inflammation and narrowing, as well as blood clots."
In a paper published last month in the early, online version of Current Opinion in Hematology, he and co-principal investigator Daniel B. Kim-Shapiro, Ph.D., professor of physics, Harbert Family Distinguished Chair, and director of the Translational Science Center at Wake Forest, reviewed experiments that show even low levels of red cell micro-particles and free hemoglobin scavenge nitric oxide, severely reducing its bioavailability.
"It's possible that an agent that increases nitric oxide levels, such as sodium nitrite, could be added to banked blood or given directly to transfusion patients to compensate for the potential complications of a storage lesion," noted Dr. Kim-Shapiro.
Drs. Gladwin and Kim-Shapiro have successfully collaborated during the last 10 years to evaluate how the nitric oxide, a molecule that causes blood vessels to dilate, interacts with hemoglobin in red blood cells. Their new grant, which was awarded by the National Heart, Lung and Blood Institute of the National Institutes of Health, aims to examine the role of oxidative damage, micro-particle formation and red cell destruction-both during blood storage and after transfusion-in lab, animal and human studies; to explore key enzymes in the nitric oxide biochemical pathway; and to develop treatments to improve the quality and function of stored blood.
Source: Wake Forest University