$3.2 million for two shock-related studies

A Virginia Commonwealth University research group has been awarded $3.2 million in federal grants for two shock-related studies, one with battlefield implications and the other for emergency medicine.

The U.S. Department of Defense awarded the VCU Reanimation Engineering Shock Center, or VCURES, a $1.3 million cooperative agreement to study and design a way for soldiers injured in combat to survive devastating blood loss when medical facilities are far away. And the National Institutes of Health awarded VCURES a $1.9 million grant to study how oxygen is transported by the tiniest blood vessels of the body during severe hemorrhage and resuscitation.

The DOD grant will expand on research that VCURES has been doing with the military to develop a metabolic engineering strategy to reduce the body’s need for oxygen after traumatic injury. That strategy now will be extended to change the rate of oxygen use and delivery by organ tissue at the cellular level when a soldier has experienced severe blood loss and when blood transfusion is not available for several hours.

Severe blood loss deprives the body’s vital organs of oxygen, resulting in organ damage, organ failure and eventually, death. Military combatants are particularly vulnerable to devastating blood loss following a battlefield injury.

R. Wayne Barbee Ph.D., senior VCURES fellow and the study’s principal investigator, said that unlike traumatic injuries that occur in a civilian setting, injured soldiers usually face limited surgical capabilities on the battlefield and the lack of a true golden hour for receiving life-saving treatment. Barbee calls the golden hour the important first hour following a traumatic injury when medical intervention produces the best results.

“Hemorrhage continues to be the leading cause of death on the battlefield,” said Barbee, an assistant professor in emergency medicine who has a second appointment in physiology. “Military field medics are limited in what they can carry, and we want a solution that allows soldiers to survive for three to six hours until medical care can be reached.

“Our goal is to create a physical state where cells need less oxygen and we are able to extend the life of organs,” said Kevin R. Ward, M.D., associate professor of emergency medicine and physiology, associate VCURES director and co-investigator for the grant. “We are looking in many different areas for clues – drawing on sophisticated models in a lab and studying the biology of several types of hibernating species.”

The NIH grant, a four-year award from the agency’s National Heart Lung and Blood Institute, will be used to understand the mechanisms of microcirculation that control the supply of oxygen to the cells of the body. Researchers are particularly 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.

Paramedics and other first responders often provide saline solution to a bleeding victim to stabilize that patient and 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 of oxygen in blood is carried in plasma.

Senior VCURES Fellow Roland N. Pittman, Ph.D., and the study’s principal investigator, said that changing the blood-delivery equation can affect how oxygen gets to the cells of vital organs and tissue.

“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,” Pittman 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,” he 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.

“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.”

VCURES is a multidisciplinary collaborative effort among clinicians, basic scientists and engineers of diverse backgrounds at the VCU medical campus and the Monroe Park campus to improve the survival from the disease state called shock. This includes its prevention, pathophysiologic basis, diagnosis and treatment.