VCU Receives $1.9 Million NIH Grant to Study Microcirculatory Response to Hemorrhage

By Michael Ford
University News Service

Virginia Commonwealth University researchers have received a $1.9 million grant from the National Institutes of Health to study how oxygen is transported by the tiniest blood vessels during severe hemorrhage and resuscitation.

The four-year grant from the NIH’s National Heart Lung and Blood Institute will be used by a research team at the Virginia Commonwealth University Reanimation Engineering Shock Center, known as VCURES, to understand the mechanisms of microcirculation, which controls the supply of oxygen to the body’s cells. Researchers particularly are interested in oxygen delivery between tiny blood vessels and organ tissue during severe blood loss and during the period of time when life-saving interventions to stabilize a patient occur.

Severe blood loss deprives the body’s vital organs of oxygen, resulting in organ damage, organ failure and eventually, death. Paramedics and other first responders often stabilize a bleeding patient with saline solution to return blood volume levels to normal. However, this does nothing to assist with oxygen delivery. Two of the major components in blood, red blood cells and plasma, exist in a delicate balance. The red blood cells contain hemoglobin molecules that transport 98 percent of the oxygen in blood. The other 2 percent is carried in plasma.

Senior VCURES Fellow Roland N. Pittman, Ph.D., the study’s principal investigator, said blood components exist in a delicate balance and are part of the complex microcirculatory system that has a lot of backup redundancies. Once part of the blood-delivery equation is changed, the method by which oxygen gets to the cells can be affected.

“It solves part of the problem, but it creates another problem by spreading the oxygen giving red blood cells farther apart,” said Pittman, a professor of physiology, emergency medicine and biomedical engineering in VCU’s School of Medicine. “A blood transfusion adds red blood cells and should improve oxygen delivery to tissues, although this does not always happen.

“We need to be able to see how close red blood cells exist in blood before hemorrhage and determine how much we can spread them out with a saline intervention before oxygen delivery to vital organs begins to fall off dramatically,” he said.

Pittman has developed an optical technique to measure oxygen flow in blood vessels less than 100 microns in diameter, capillaries so small they are visible only under a microscope.

“We’re talking about one-tenth of one-tenth of a millimeter, about the size of a single red blood cell,” Pittman said. “This is the site where oxygen moves from the red blood cell to cells in muscles, organs and other body tissue.”

The new challenge is to develop an optical technique that also measures nitric oxide at different places in the microcirculatory system. Pittman said this is important because in low concentration, nitric oxide helps keep blood vessels open.

“During hemorrhage, the tiniest blood vessels constrict, choking off blood flow and oxygen delivery,” said Pittman. “As we learn more about efficient oxygen delivery and nitric oxide levels in the microcirculatory system, we can develop a resuscitation fluid that keeps the largest number of oxygen delivering capillaries open.”

The research project will provide insight into how commonly used resuscitation fluids and new fluids currently in development either improve or worsen survival.

Other members of the research team are:

• Ivo Torres Filho, M.D., Ph.D., associate professor of anesthesiology, physiology and emergency medicine, director of VCURES Clinical Microcirculatory Laboratory and co-principal investigator
• R. Wayne Barbee, Ph.D., associate professor of emergency medicine and physiology and senior VCURES fellow
• Aleksander Golub, Ph.D., associate professor of physiology and VCURES fellow
• Aleksander Popel, Ph.D., professor of biomedical engineering, Johns Hopkins University
• Kevin Ward, M.D., associate professor of emergency medicine and physiology, associate VCURES director

VCURES was initially developed as a collaborative effort between the departments of anesthesiology, emergency medicine and surgery. This endeavor has grown to draw on the expertise from many additional departments, centers and schools at VCU. This multi-disciplinary collaboration among physicians, basic scientists and engineers creates many opportunities for researching partnerships where none have traditionally existed.