Vital Organ Tissue Oxygenation After Serial Normovolemic Exchange Transfusion with HBOC-201 in Anesthetized Swine

Abstract

This study determined the effects of serial, normovolemic, stepwise exchange transfusions with either 6% human serum albumin (HSA) or the hemoglobin-based oxygen carrier, HBOC-201, on tissue oxygenation of the heart, brain and kidney in intact anaesthetized pigs. Exchange transfusions to 10%, 30% and 50% of the pigs total blood volume were completed at a withdrawal rate of 1.0 ml/kg/min followed by an infusion rate of 0.5 ml/kg/min of HBOC-201 or iso-oncotically matched 6% HSA. Measurements included invasive systemic hemodynamic (blood pressures, left ventricular end diastolic pressure [LVEDP]), hematolic (hemoglobin, hematocrit, methemoglobin), acid-base (pH, pCO2) and biochemistry (serum lactate) measurements. Brain and kidney tissue oxygenation (tPO2) were determined by electron paramagnetic resonance (EPR) and heart tPO2 by O2 sensitive fiber optic probe. The main results demonstrated that tPO2 after HBOC-201 remained stable despite significant decreases in hematocrit and changing hemodynamics. In vivo tPO2 measurements (heart tPO2 average ≥ 22 mm Hg; brain tPO2 average ≥ 8 mmHg; and kidney tPO2 average ≥10 mmHg) were maintained in all groups at all times. Blood pressures were 20–30 mm Hg higher after HBOC-201 compared to HSA controls. Heart rate and LVEDP were not different among treatment groups. In conclusion, the administration of HBOC-201 maintained tPO2 in three vital organs after profound hemodilution.

Haemoglobin-based oxygen carriers and myocardial infarction

“…Furthermore, no thrombosis or infarction was detected after DCLHb administration. Lesion incidence and severity were reduced by polymerization [81], consistent with reports that such findings have not been observed after the infusion of larger HBOCs [82,83]. In the context of MI, it is interesting to note that the correlation between molecular size and MI incidence in human clinical trials is opposite to that observed with the formation of these microscopic findings.…”

A case study of 10 patients administered HBOC‐201 in high doses over a prolonged period: outcomes during severe anemia when transfusion is not an option

“…In the systemic circulation, decreases in CO during HBOC‐201 infusion are due to vasoconstriction in skeletal muscle vasculature rather than ischemia‐ or hypoxia‐induced cardiac dysfunction . Normal blood flow and tissue oxygenation are maintained in vital organs, including in particular, the heart, brain, and kidneys . Hence, HBOC‐201 induces a redistribution of systemic blood from skeletal muscles to vital organs.…”

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

“…An explanation could be that these earlier studies did not use an iso-oncotic colloid or because these studies also included the influences of hypovolemia, anemia or tissue trauma. A literature search for research pertaining to HBOC-201 and iso-oncotic HSA revealed only two other studies (Mongan et al, 2009; Muir et al, 2011). Both investigators utilized the same hemodilution model where swine underwent three transfusions to attain volume exchanges of 10%, 30% and 50%.…”

“…Information regarding viscosity (measured at room temperature) and oxygen affinity was provided by OPK Biotech. Human Serum Albumin (25% HSA, ZLB Behring AG, Berne, Switzerland) was diluted with normal saline to 5.9% to provide an iso-oncotic volume control solution to HBOC-201 (Mongan et al, 2009; Muir et al, 2011). …”