Title:Adverse HBOC-Endothelial Dysfunction Synergism: A Possible Contributor to Adverse Clinical Outcomes?
Volume: 9
Issue: 3
Author(s): George P. Biro
Affiliation:
Keywords:
Angiotensin, atherosclerosis, coronary vascular disease, diabetes, endothelial dysfunction, endothelial function,
endothelium, endothelin, guanylyl cyclase, hemoglobin-based oxygen carrier, hemoglobin, hypertension, nitric oxide, nitric oxide synthase, peroxynitrite, prostaglandins, reactive oxygen species, vascular smooth muscle, vasoconstriction, vasodilation.
Abstract: Adverse outcomes in clinical trials on Hemoglobin Based Oxygen Carriers (HBOCs) appear to have occurred
more frequently in HBOC treated than in control treated subjects. The differential may be related to many factors, including
study complexity and compliance issues. Adverse outcomes also appear to be related to chronic comorbidities in subjects
undergoing elective surgery. Frequently occurring comorbidities in these populations are those related to aging, cardiovascular
and metabolic disease (hypertension, atherosclerosis, diabetes, etc.). These are highly prevalent among many
population subsets. These conditions have been extensively studied and are characterized by dysfunction of important endothelial
vasoregulatory mechanisms, including impaired nitric oxide bioavailability, excessive generation of reactive
oxygen species (ROS) and possibly enhanced vasoconstrictor mechanisms. Although less extensively studied, HBOCs
have properties that may have an important amplifying effect upon mechanisms operating in endothelial dysfunction, by
scavenging nitric oxide, generating further excess of ROS which in turn react with nitric oxide, inhibit nitric oxide synthase
and possibly stimulate the release of vasoconstrictors such as endothelin. It is likely that amplification of vasoconstrictor
effects is not uniformly operative in all vascular beds, and that some protective autoregulatory mechanisms maintain
sufficient blood flow in vital organs as long as sufficient vasodilator reserve is available. When the latter is exhausted
in the presence of arterial disease with physical obstructions, blood flow to vital organs may become compromised. This
paper suggests avenues of further exploration to elucidate whether the combination of HBOC and endothelial dysfunction
is a contributing factor in HBOC related adverse outcomes.