Purification of Concentrated Hemoglobin Using Organic Solvent and Heat Treatment

Sakai, Hiromi; Takeoka, Shinji; Yokohama, Hiroaki; Seino, Yuriko; Nishide, Hiroyuki; Tsuchida, Eishun

doi:10.1006/prep.1993.1074

Cited by 82 publications

(72 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HbV was prepared as reported previously (33,40,45,47), with slight modifications. Human Hb solution was obtained through purification of outdated RBCs provided by the Japanese Red Cross Society (Tokyo, Japan).…”

Section: Preparations Of Hbv Stroma-free Hb Polymerized Hb and Hummentioning

confidence: 99%

“…Gas-permeable narrow tubes enable the measurement of the O 2 -releasing rates of HBOCs and RBCs during their flow through the tubes at a practical [Hb] (6-13 g/dl) (18,27,40,48). As described in this paper, we used gas-permeable narrow tubes made of perfluorinated polymer to study not only O 2 release, but also NO-binding and CO-binding profiles, all of which should relate to the mechanisms of vasoactive properties of cell-free HBOCs and the vasoinactive properties of cellular HbV proposed above.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes

Sakai

Okuda

Sato

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Sakai H, Okuda N, Sato A, Yamaue T, Takeoka S, Tsuchida E. Hemoglobin encapsulation in vesicles retards NO and CO binding and O2 release when perfused through narrow gas-permeable tubes. Am J Physiol Heart Circ Physiol 298: H956 -H965, 2010. First published December 31, 2009 doi:10.1152/ajpheart.00741.2009.-Intravenous administration of cell-free Hb induces vasoconstriction and circulatory disorders, presumably because of the intrinsic affinities to endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors and because of the facilitated O2 release that might induce autoregulatory vasoconstriction. We examined these gas reactions when Hb-containing solutions of four kinds were perfused through artificial narrow tubes at a practical Hb concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (Poly BHb), encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were perfused through a gas-permeable narrow tube (25 m inner diameter) at 1 mm/s centerline velocity. The level of reactions was determined microscopically based on the visible-light absorption spectrum of Hb. When the tube was immersed in NO and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb) and PolyBHb in the tube was faster than those of HbV and RBCs, and HbV and RBCs showed almost identical binding rates. When the tube was immersed in a N2 atmosphere, oxygenated Hb and PolyBHb showed much faster O 2 release than did HbV and RBCs. PolyBHb showed a faster reaction than Hb because of the lower O2 affinity of PolyBHb than Hb. The diffusion process of the particles was simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large-dimension HbV shows no such rapid diffusion. The purely physicochemical differences in diffusivity of the particles and the resulting reactivity with gas molecules are one factor inducing biological vasoconstriction of Hb-based oxygen carriers. microcirculation; blood substitutes; gas biology; liposome; erythrocytes CELL-FREE, HEMOGLOBIN-BASED oxygen carriers (HBOCs) have been developed for use as transfusion alternatives. Some examples are intramolecular cross-linked Hb, polymerized Hb, and polyethylene glycol conjugated Hbs (5). The realization of HBOCs has long been anticipated, because they are free of pathogens and blood-type antigens and are storable for a long time for using at emergency situations. Some are in the final stage of clinical trials (23). The major remaining hurdle before clinical approval of this earliest generation of HBOCs is vasoconstriction and resulting hypertension, which are presumably attributable to the high reactivity of Hb with endothelium-derived nitric oxide (NO) (26,28,55). It has been suggested that small molecular Hbs permeate across the endothelial cell layer to the space near by the smooth muscle and inactivate NO. However, cellular Hb-vesicles (HbV) that encapsulate concentrated Hb solution in phospholipid vesicles (37) ind...

show abstract

Section: Preparations Of Hbv Stroma-free Hb Polymerized Hb and Hummentioning

confidence: 99%

mentioning

confidence: 99%

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes

Sakai

Okuda

Sato

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…In fact, the pharmacological effects of HbV, injected into rats with hemorrhagic shock, have been reported to be equivalent to those of RBCs (Sakai et al, 2004b). In addition, HbV have been shown to possess a number of positive characteristics such as the absence of viral contamination (Sakai et al, 1993;Abe et al, 2006), a long-term storage period of more than 2 years at room temperature (Goda et al, 1998;Sakai et al, 2000b;Abe et al, 2007), and low toxicity [blood compatibility, and suppressed nephrotoxicity induced by the dimeric form of Hb and hypertension induced by the direct interaction of Hb with nitric oxide (NO) and CO] (Sakai et al, 2000a). Moreover, HbV suspended in a solution of human serum albumin can be used to regulate rheological properties (e.g., viscosity and colloid osmotic pressure) (Sakai et al, 2000c(Sakai et al, , 2004b.…”

mentioning

confidence: 99%

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Taguchi

Urata²,

Anraku³

et al. 2009

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…HbV has been shown to possess a number of positive characteristics: the absence of viral contamination (Sakai et al, 1993), a long-term storage period of more than 2 years at room temperature (Sakai et al, 2000b;Sou et al, 2000), low toxicity (blood compatibility, no nephrotoxicity) (Sakai et al, 2000a), and good metabolic performance (Taguchi et al, 2009b(Taguchi et al, , 2010. Moreover, the pharmacological effects of HbVs have been reported to be equivalent to that of RBCs, when evaluated in a model of hemorrhagic shock in rats (Sakai et al, 2004b.…”

Section: Introductionmentioning

confidence: 99%

Fluid Resuscitation with Hemoglobin Vesicles PreventsEscherichia coliGrowth via Complement Activation in a Hemorrhagic Shock Rat Model

Taguchi¹,

Ogaki²,

Watanabe³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Hemoglobin vesicles (HbVs) could serve as a substitute for red blood cells (RBCs) in resuscitation from massive hemorrhage. A massive transfusion of RBCs can increase the risk of infection, which is not caused by contaminating micro-organisms in the transfused RBCs but by a breakdown of the host defense system. We previously found that complement activity was increased after resuscitation with HbVs at a putative dose in a rat model of hemorrhagic shock. It is known that complement system plays a key role in host defense in the embryonic stage. Therefore, the objective of this study was to address whether the suppression of bacterial infections in hemorrhagic shock rats was a result of increased complement activity after massive HbV transfusion. For this purpose, Escherichia coli were incubated with plasma samples obtained from a rat model of hemorrhagic shock resuscitated by HbVs or RBCs, and bacterial growth was determined under ex vivo conditions. As a result, E. coli growth was found to be suppressed by increased complement activity, mediated by the production of IgM from spleen. However, this antibacterial activity disappeared when the E. coli were treated with complement-inactivated plasma obtained from splenoctomized rats. In addition, the resuscitation of HbVs from hemorrhagic shock increased the survival rate and viable bacterial counts in blood in cecum ligation and puncture rats, a sepsis model. In conclusion, the resuscitation of HbVs in the rat model of hemorrhagic shock suppresses bacterial growth via complement activation induced by IgM.

show abstract

Purification of Concentrated Hemoglobin Using Organic Solvent and Heat Treatment

Cited by 82 publications

References 0 publications

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Fluid Resuscitation with Hemoglobin Vesicles PreventsEscherichia coliGrowth via Complement Activation in a Hemorrhagic Shock Rat Model

Contact Info

Product

Resources

About

Purification of Concentrated Hemoglobin Using Organic Solvent and Heat Treatment

Cited by 82 publications

References 0 publications

Hemoglobin encapsulation in vesicles retards NO and CO binding and O2release when perfused through narrow gas-permeable tubes

Hemoglobin encapsulation in vesicles retards NO and CO binding and O2release when perfused through narrow gas-permeable tubes

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Fluid Resuscitation with Hemoglobin Vesicles PreventsEscherichia coliGrowth via Complement Activation in a Hemorrhagic Shock Rat Model

Contact Info

Product

Resources

About

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes

Hemoglobin encapsulation in vesicles retards NO and CO binding and O₂release when perfused through narrow gas-permeable tubes