Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with altered oxygen affinity and viscosity on systemic and microcirculatory variables in a top-load rat model

Abstract

The effects of a polymerized bovine hemoglobin-based oxygen carrier (HBOC) and two derivatives on arteriolar vasoactivity and tissue oxygen tension were explored by administering HBOC in a dose-response fashion to normovolemic rats. The effect of oxygen affinity (P50) and viscosity were also explored, where the P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50 and LP50A) were as follows: 40 mmHg and 3.0 cP (HBOC-20l); 18 mmHg and 4.4 cP (MP50); and 17 mmHg and 12.1 cP (LP50A). Anesthetized male Sprague-Dawley rats (N = 32) were randomized to receive one of the HBOC solutions, and were administered four infusions that increased in concentration for each dose (2, 22, 230 and 780 mg/kg, IV). Data were compared to rats receiving an equivalent volume for each of the four infusions (0.4, 0.4, 3.8, 13.1 ml/kg, IV) of iso-oncotic 5.9% human serum albumin (HSA). Increasing doses of either HBOC solutions or HSA were associated with increasing MAP. Doses 3 and 4 of HBOC-201, MP50 and HSA produced significant increases in MAP, whereas similar increases began at a lower dose (Dose 2) with LP50A. There were no significant changes in arteriolar diameters at any dose for any group. Interstitial partial pressure of oxygen (ISF PO2) remained unchanged for HBOC-201, MP50 and HSA, but LP50A caused a significant decrease in ISF PO2 compared to baseline after Doses 3 and 4. In conclusion, there was no evidence that HBOC-201 would perform better with increased oxygen affinity (40 to 18 mmHg) or viscosity (3.0 to 4.4 cP).

Skeletal muscle interstitial O2 pressures: bridging the gap between the capillary and myocyte

“…Assessment of interstitial oxygenation via phosphorescence quenching has yielded other important advances in our understanding of skeletal muscle function and oxidative metabolism. Pittman and colleagues have employed muscle PO 2 is measurements to evaluate the viability of hemoglobin‐based oxygen carriers and their effects on microcirculatory function . Moreover, combining phosphorescence quenching microscopy with local blood flow arrest (via pneumatic tissue compression) permitted evaluation of resting and contracting muscle O 2 utilization as well as the O 2 dependence of respiration .…”

Apohemoglobin-haptoglobin complexes attenuate the hypertensive response to low-molecular-weight polymerized hemoglobin

“…43 The relative changes in MAP and vessel tone compared with baseline in the saline treatment group were, on average, comparable to the changes observed after a top-load dose of HBOC-201. 44 This outcome was expected, given that the LMW PolyHb molecules used in this study had similar size distributions and O 2 affinity compared with HBOC-201. The relatively similar properties of the PolyHb produced for this study make it a promising surrogate for previous commercial products.…”

The effect of pPolyHb on hemodynamic stability and mesenteric microcirculation in a rat model of hemorrhagic shock

“…Another study compared the effects on microvessels of four fluids: 5.9% human serum albumin (HSA); HBOC-201; HBOC-201 with a P50 of 18 mmHg(MP50); and an HBOC-201 with P50 of 17 mmHg and higher viscosity(LP50). Arteriolar diameters were not significantly changed following administration of any of those fluids (Song et al 2014).…”