Hemoglobin-based oxygen carrier-201 (HBOC) was developed as a resuscitative fluid but concerns exist over
potentially adverse vasoconstriction. This study evaluated whether concurrent IV (intra venous) N-acetyl-L-cysteine
(NAC) or hyaluronic acid (HA) would attenuate HBOC-associated vasoconstriction, assessed by systemic blood pressures
and cerebral pial microvasculature, when administered to healthy, anesthetized rats.
Rats (8-9/group) received a 30 min infusion of 3 ml/kg HBOC, HBOC plus 600 mg/kg NAC (HBOC/NAC), HBOC plus
1.5 mg/kg HA (HBOC/HA) or 3 ml/kg Albumin. Mean (MAP) and systolic (SBP) blood pressures, blood chemistries and
cerebral pial vessel diameters were measured at baseline, end of infusion, and intermittently for an additional 90 min.
HBOC caused immediate and sustained increases in SBP and MAP (35.3 ± 3.6 and 29.1 ± 2.5 mm Hg peak increases
above baseline, respectively; mean ± SEM) and immediate but progressive vasoconstriction (11 µm maximum reduction)
in medium-sized (50-100 µm) pial arterioles. When NAC was co-administered, blood pressure changes were attenuated
and vessel changes were abolished. Similar trends were noted with co-administration of HA but were not statistically different
from HBOC-alone. Small-sized (< 50 µm) pial vessels and blood parameters showed no differences from baseline
or among groups. No adverse clinical signs were observed.
We demonstrated that it is possible for adjuvant drugs to reduce the vasoconstriction associated with HBOC-201. Coinfusion
of the anti-oxidant NAC mitigated HBOC-201-associated increases in blood pressures and vasoconstriction in
medium-sized cerebral pial vessels. The drag-reducing polymer HA may be more effective at a higher dose as a similar
but non-significant trend was observed.