Virginia T. Rentko

Absence of immunopathology associated with repeated IV administration of bovine Hb-based oxygen carrier in dogs

BACKGROUND: A Hb‐based oxygen carrier, HBOC‐301, is licensed by the FDA for use as a single‐dose product to treat anemia in canines. The objective of this study was to investigate the immunopathologic consequences of multiple doses of HBOC‐301.

The Effects of Decreasing Low-molecular Weight Hemoglobin Components of Hemoglobin-based Oxygen Carriers in Swine With Hemorrhagic Shock

BACKGROUND Some hemoglobin-based oxygen carriers (HBOCs) improve outcome in animal models of hemorrhagic shock (HS) in comparison with standard asanguinous resuscitation fluids. Nevertheless, concern about intrinsic vasoactivity, linked in part to low-molecular weight (MW) hemoglobin (Hb), has slowed HBOC development. We assessed the impact of decreasing the low-MW Hb component of bovine HBOC on vasoactivity in severe HS. METHODS Anesthetized invasively monitored swine were hemorrhaged 55% blood volume and resuscitated with bovine HBOC containing 31% (31 TD [HBOC-301]), 2% (2 TD [HBOC-201]), or 0.4% (0.4 TD) low-MW Hb. Pigs received four 10 mL/kg infusions over 60 minutes, hospital arrival was simulated at 75 minutes, organ blood flow (BF) was evaluated by microsphere injection, and monitoring was continued for 4 hours followed by complete necrotic evaluation. RESULTS There were few differences between 2 TD and 0.4 TD. Thirty-one TD pigs had higher systemic and pulmonary blood pressure (BP), systemic vascular resistance index, and pulmonary artery wedge pressure, compared with 2 TD or 0.4 TD (p < 0.01); however, pigs in all groups had at least mildly elevated BP. Transcutaneous tissue oxygenation, base excess, and mixed venous oxygen saturation were similar across groups; lactate and methemoglobin were highest with 0.4 TD (p < 0.03). There were no group differences in BF. Over time, myocardial BF increased and hepatic BF decreased in all groups (for 31 TD, p < 0.05); renal BF was unchanged in all groups. There were no group differences in heart, lung, or liver histopathology, and survival. CONCLUSIONS Although purification from 31% to 2% low-MW Hb content significantly decreased vasoactive responses, further purification to 0.4% had no additional clinically measurable effects in severe HS. If further diminution in HBOC vasoactivity is desired for use in HS, additional technical approaches may be required.

Clinical application of a hemoglobin-based oxygen-carrying solution

Oxyglobin, a hemoglobin-based oxygen-carrying fluid, is indicated in the treatment of anemia in dogs and may be life saving if compatible red blood cells are not available for transfusion. The colloidal properties of Oxyglobin allow for expansion of the circulatory volume, which may be helpful in patients with hypovolemia, especially hemorrhagic shock. Oxyglobins colloidal properties can also lead to circulatory overload, with development of pulmonary edema and pleural effusion, however, necessitating careful monitoring of the rate of administration and of the respiratory rate and effort of the patient. Measurement of total or plasma hemoglobin concentration can be used as an aid in monitoring patients receiving Oxyglobin.

Regional blood flow after serial normovolemic exchange transfusion with HBOC-201 (Hemopure) in anesthetized swine.

BACKGROUND This study determined individual organ blood flows and global hemodynamic, oxygen delivery and consumption parameters after normovolemic exchange transfusions with the hemoglobin based oxygen carrier (HBOC)-201 in a lightly anesthetized swine model. METHODS The exchange transfusions were performed as a stepped reduction in blood volume to attain volume exchanges of 10%, 30%, and 50% with a 1:1 replacement with HBOC-201 (n = 8) or oncotically matched 5.9% human serum albumin (HSA, n = 8). Four additional animals served as time controls. RESULTS There was no change in the regional blood flows in 8 of 9 organs (brain, heart, kidney, liver, pancreas, gall bladder, small intestines, large intestines, and skeletal muscle) after HBOC-201 compared with controls; only skeletal muscle blood flow decreased. In contrast, with HSA, blood flow increased 150% to 200% of baseline in all organs except muscle where blood flow was unchanged. HBOC-201 effectively restored oxygen delivery after these exchanges. The mean arterial pressure increases in the HBOC-201 group were within 15% to 20% of baseline during the initial 10% exchange and similar to controls during subsequent exchanges. Although peak pulmonary arterial pressure increases in the HBOC-201 group were 10 mm Hg to 15 mm Hg above baseline, cardiac index was unchanged. There were no differences in global oxygen consumption, consistent with unchanged regional blood flow and suggests intact physiologic coupling of oxygen delivery and consumption that was unimpaired by local vasoconstriction. This is in contrast to significant changes of increased cardiac index, decreased arterial pressure, decreased oxygen content, and increased oxygen extraction ratio to maintain normal oxygen consumption in the HSA group. CONCLUSION Although the use of HBOC-201 caused alterations in systemic (minimal) and pulmonary (modest) pressures, these changes had no consequence on regional organ blood flow.