Effects of Hemoglobin-Based Oxygen Carriers Studied
Research provides insight into vasoconstriction side effect of HBOCs (artificial blood)
MONDAY, March 15 (HealthDay News) -- Vasoconstrictor side effects of a hemoglobin-based oxygen carrier (HBOC) are not improved with reduction of low molecular weight hemoglobin concentrations to less than 1 percent, and are worse in animals with reduced nitric oxide levels associated with endothelial dysfunction due to diabetes or a high-fat diet, according to a study in the March issue of Anesthesiology. The findings give new insights into how to better understand and utilize these HBOCs, otherwise known as artificial blood.
Binglan Yu, Ph.D., of Harvard Medical School at Massachusetts General Hospital in Boston, and colleagues infused low-molecular weight HBOCs -- PolyHeme (1.08 g hemoglobin/kg) or murine tetrameric hemoglobin (0.48 g hemoglobin/kg) -- into awake healthy lambs, awake mice and anesthetized mice, including mice with diabetes and those fed on a high-fat diet.
The researchers found that the PolyHeme infusion did not result in systemic hypertension in the awake lambs, but did cause acute systemic and pulmonary vasoconstriction. In the healthy mice, HBOC infusion did not result in systemic hypertension but did cause severe systemic vasoconstriction in the mice with endothelial dysfunction either from diabetes or the high-fat diet. In vitro studies confirmed that the mice with diabetes had an enhanced vasoconstrictor response to the HBOC. The authors note that pretreatment with inhaled nitric oxide mitigated hypertension and vasoconstriction in the animals.
"Reduction of low molecular weight hemoglobin concentrations to less than 1 percent is insufficient to abrogate the vasoconstrictor effects of HBOC infusion in healthy awake sheep or in mice with reduced vascular nitric oxide levels associated with endothelial dysfunction. These findings suggest that testing HBOCs in animals with endothelial dysfunction can provide a more sensitive indication of their potential vasoconstrictor effects," the authors write.
One study author has received royalties for a patent related to inhaled nitric oxide, and another has received grants for the study of inhaled nitric oxide. Northfield Corporation funded the animal costs and provided the PolyHeme.