Acellular Hemoglobin-Based Oxygen Carrier Induced Vasoactivity: A Brief Review of Potential Pharmacologic Remedies

Hemoglobin-based oxygen carriers (HBOCs) are currently in late phase clinical development as potential red blood cell substitutes. However, in recent clinical trials, most HBOC products have elicited vasoconstriction and blood pressure elevation. Mechanisms of the HBOC-mediated vasoactivity have not been fully elucidated. However, regardless of mechanisms involved, observations from preclinical and clinical studies indicate that the HBOC-mediated vasoconstriction/blood pressure elevation can be attenuated by conventional and newer anti-hypertensive agents and vasodilators. These include calcium channel blockers, nitrovasodilators, ACE inhibitors, selective PDE inhibitors and inhalation of gaseous NO or nebulized nitrites. There is little information available regarding the safety and effectiveness of these agents when used for treatment of HBOC-mediated vasoconstriction and BP elevation. In this review we identify some potentially useful pharmacologic agents and discuss potential issues involved in their use with HBOCs.