Study to restrict hemoglobin-based oxygen carriers

A study published in the March 2010 issue of the journal Anesthesiology gives researchers new insights in how to better understand and control a severe side effect of hemoglobin-based oxygen carriers (HBOCs), often referred to as "artificial blood."

Binglan Yu, Ph.D., an Instructor in Anesthesia at Harvard Medical School and Massachusetts General Hospital, said that HBOCs are known to cause vasoconstriction, or narrowing of the blood vessels, which can lead to cardiovascular complications, especially in critically ill patients.

"The mortality for patients or soldiers who hemorrhage without receiving a red blood cell transfusion is high," said Dr. Yu. "There is a critical unmet need for an alternative to red blood cell transfusion when red blood cells are not available. At present, after decades of research, there is no safe and effective HBOC for the treatment of hemorrhage shock."

Vasoconstriction occurs because HBOCs have a tendency to scavenge, or in a sense, consume, nitric oxide, which is a crucial gas molecule used by all mammals to maintain a healthy circulation. When nitric oxide is taken away, blood vessels become constricted and blood clotting is activated.

In the current study, headed by Dr. Warren Zapol, the Reginald Jenney Professor of Anesthesia, and Dr. Kenneth Bloch, William Thomas Green Morton Professor of Anesthesia at Harvard Medical School, Dr. Yu and her group used a specially designed HBOC that does not typically cause vasoconstriction in healthy animals because of its reduced molecular weight. This reduced molecular weight HBOC helps to decrease nitric oxide scavenging.

In the past, HBOCs were tested on normal sheep and mice and on other animals without diabetic cardiovascular disease. The researchers have now found that animals with cardiovascular disease are much more sensitive to the adverse effects of HBOCs because unhealthy animals produce less of the crucial nitric oxide needed for good cardiac and vascular health.

"These findings may provide an explanation as to why HBOC infusion causes hypertension in some patients (presumably those with diabetes or those who are overweight) and not in others, and provides a basis for understanding the higher mortality and increased frequency of heart attacks and strokes seen in some HBOC recipients," said Dr. Yu.

Dr. Yu's team also discovered that animals with cardiovascular disease which were allowed to breathe nitric oxide before being given the HBOCs did not experience either vasoconstriction or other cardiac-related side effects.

"In the future, HBOCs should be routinely evaluated in animals that have reduced levels of nitric oxide to ensure the safety of the HBOC for humans who may have known or hidden metabolic or vascular diseases associated with such conditions as diabetes or obesity," said Dr. Yu.