Compatibility in vitro of albumin‐heme (O₂ carrier) with blood cell components

Abstract

Recombinant human serum albumin including 2-[8-[N-(2-methylimidazolyl)]octanoyloxymethyl]-5,10,15,20-tetrakis(alpha,alpha,alpha,alpha-o-pivaloylamino)phenylporphinatoiron(II) (albumin-heme; rHSA-FeP) is a synthetic hemoprotein that has sufficient capability to reversibly bind and release O(2) under physiological conditions (pH 7.3, 37 degrees C) similar to hemoglobin and myoglobin. In order to use this albumin-based O(2) carrier as a new class of red blood cell substitutes, its compatibility with blood cell components carefully was investigated in vitro. After the addition of the rHSA-FeP solution into whole blood at 10, 20, and 44 vol %, the FeP concentration in the plasma phase remained constant for 6 h at 37 degrees C in each group, and no significant time dependence was observed in the numbers of red blood cells, white blood cells, or platelets. The microscopic observations clearly showed that the shapes of the red blood cells had not been deformed during the measurement period. With respect to the blood coagulation parameters (prothrombin time and activated partial thromboplastin time), the coexistence of rHSA-FeP had only a negligibly small influence. Also the blood compatibility under dynamic flow conditions was evaluated using a microchannel array flow analyzer. All these results suggest that the albumin-heme has no effect on the morphology of blood cell components in vitro.

Influence of O2‐carrying plasma hemoprotein “albumin‐heme” on complement system and platelet activation in vitro and physiological responses to exchange transfusion

“…The recombinant human serum albumin (HSA, 25 wt %) was obtained from the NIPRO (Osaka). The HSA‐FeP solution ([HSA]: 5.0 wt %, pH 7.4, [FeP]: 3.0 m M , COP: 21 mmHg, osmolarity: 300 mOsm, viscosity: 1.1 cP, endotoxin: <0.1 EU/mL, O 2 ‐binding affinity ( P 1/2 O 2 ): 33 Torr) was prepared using our previously reported procedure 8…”

“…We have also developed a unique albumin‐based O 2 ‐carrier “albumin‐heme,” which is composed of recombinant human serum albumin (HSA) including synthetic heme (2‐[8‐{ N ‐(2‐methylimidazolyl)} octanoyloxymethyl]‐5,10,15,20‐tetrakis(α,α,α,α‐ o ‐pivalamido)phenylporphinatoiron(II)) (FeP, Scheme ) (HSA‐FeP) 5–7. The HSA‐FeP solution has a high compatibility with the blood cell components, and its O 2 ‐transporting capability was evaluated by animal experiments 8, 9. Nevertheless, animal studies cannot predict the potential effect on human responses.…”

Exchange transfusion with entirely synthetic red‐cell substitute albumin‐heme into rats: Physiological responses and blood biochemical tests

“…The 5 11 The red-colored rHSA-heme solution was filtered with the use of DISMIC 25CS045AS just before use.…”

Polymer/Hemoglobin Assemblies: Biodegradable Oxygen Carriers for Artificial Red Blood Cells

“…The former is mainly based on human or bovine hemoglobin (Hb) to obviate renal toxicity from hemoglobin dissociation. The latter has included perfluorocarbon‐based materials4–8 and totally synthetic heme hybrids 9–16…”