Biomedical subjects

E Tsuchida

Publications and source records attributed to E Tsuchida.

108 records · Page 6Linked to original sources

PubMedDate not supplied

Reaction of nitric oxide with synthetic hemoprotein, human serum albumin incorporating tetraphenylporphinatoiron(II) derivatives.

The reaction of nitric oxide (NO) with a synthetic hemoprotein, the recombinant human serum albumin (rHSA) incorporating eight tetraphenylporphinatoiron(II) derivatives bearing a covalently linked axial base (FeP) [rHSA-FeP], has been investigated. The UV--vis absorption spectrum of the phosphate buffer solution (pH 7.3) of rHSA-FeP showed maxima at 425 and 546 nm upon the addition of NO. The carbonyl rHSA-FeP, in which FePs are six-coordinate CO-adducts, also moved to the same species after bubbling with NO gas. ESR spectroscopy revealed that the incorporated FePs in the albumin formed six-coordinate nitrosyl complexes; the proximal imidazole moiety does not dissociate from the central iron when NO binds to the trans side. The NO-binding affinity of rHSA-FeP (P(1/2)(NO), 1.7 x 10(-6) Torr, pH 7.3, 298 K) was significantly lower than that of FeP itself (P(1/2)(NO), 1.8 x 10(-8) Torr in toluene). Kinetically, this arises from the decreased association rate constant (k(on)(NO), 8.9 x 10(8) M(-1) s(-1) --> 1.5 x 10(7) M(-1) s(-1)). Since NO-association is diffusion controlled, incorporation of the synthetic heme into the albumin matrix appears to restrict the NO access to the central iron(II).

Electron Spin Resonance Spectroscopy↗

PubMedDate not supplied

Photoreduction of autooxidized albumin-heme hybrid in saline solution: revival of its O(2)-binding ability.

Recombinant human serum albumin (rHSA) incorporating 2-[8-[N-(2-methylimidazolyl)]octanoyloxymethyl]-5,10,15,20-tetrakis(alpha,alpha,alpha,alpha-o-pivalamido)phenylporphinatoiron(II)s (Fe(II)Ps) [rHSA-Fe(II)P] is a synthetic hemoprotein which can bind and release O(2) reversibly under physiological conditions (saline solution [NaCl]: 150 mM, pH 7.3) as do hemoglobin and myoglobin. However, the central ferrous ions of Fe(II)Ps are slowly oxidized to O(2)-inactive ferric forms. Based on the UV-vis. absorption spectroscopy, the majority of the autooxidized Fe(III)Ps in albumin are determined to be six-coordinate high-spin complexes with a proximal imidazole and a chloride anion, which show ligand-to-metal charge transfer (LMCT) absorption at 330 nm. Interestingly, photoirradiation of this LMCT band under an argon atmosphere led to reduction of the central ferric iron of Fe(III)P, allowing the revival of the O(2)-binding ability. The ratio of the photoreduction reached a maximum of 83%, which is probably due to the partial dissociation of the axial imidazole. The same photoirradiation under a CO atmosphere provides the corresponding carbonyl rHSA-Fe(II)P. Laser flash photolysis experiments revealed that the reduction was completed within 100 ns. The quantum yields (Phi) of these photoreductions were approximately 0.01.

Carbon Monoxide↗

PubMedDate not supplied

Surface modification of hemoglobin vesicles with poly(ethylene glycol) and effects on aggregation, viscosity, and blood flow during 90% exchange transfusion in anesthetized rats.

Poly(ethylene glycol) (PEG5000)-conjugated phosphatidylethanolamine was introduced onto the surface of hemoglobin vesicles (HbV); phospholipid vesicles encapsulating concentrated Hb (d = 0.257 +/- 0.087 micron; P50 = 32 Torr). The obtained PEG-modified HbV (HbV-PEG) was studied for use as a red cell substitute from the viewpoint of rheology, surface properties, and hemodynamics. The viscosity of the unmodified HbV suspended in saline ([Hb] = 10 g/dL) was 2.6 cP (shear rate = 358 s-1, 37 degrees C), less than that of human blood (4 cP). However, when suspended in a 5 g/dL albumin solution (HbV/ albumin), it increased to 8 cP due to the molecular interaction between albumin and vesicles, and the viscosity increased with decreasing shear rate, e.g., 37 cP at 0.58 s-1. As for the HbV-PEG/albumin, on the other hand, the viscosity was 3.5 cP at 358 s-1 and was comparable with that of human blood. Optical microscopy showed formless flocculated aggregates of the unmodified HbV, while no aggregates were confirmed for the HbV-PEG. The steric hindrance of PEG chains seemed to be effective in preventing intervesicular access and the resulting aggregation. To estimate the flow profiles in the capillaries, the suspensions were allowed to penetrate through isopore membrane filters (pore size = 0.4-8 microns, cf. capillary diameter = 4-10 microns). The penetration rate of the HbV-PEG/albumin was higher than that of the unmodified HbV/albumin due to the suppression of aggregation, whereas both of them were significantly higher than that of human blood due to the smaller size of vesicles than RBC. Ninety percent exchange transfusion was performed with the HbV-PEG/albumin or HbV/albumin in anesthetized Wistar rats (n = 6). The blood flow in the abdominal aorta increased 1.5 times, and the total peripheral resistance decreased in the HbV-PEG/albumin-administered group in comparison with the HbV/albumin group. As for the blood gas parameters, the base excess and pH remained at higher levels in the HbV-PEG/albumin group, and the O2 tension in mixed venous blood for the HbV-PEG/albumin group tended to be maintained at a higher level than that for the HbV/albumin group. Thus, the PEG modification of HbV reduced the viscosity by the suppression of aggregation and resulted in prompt blood circulation in vivo.

Adsorption↗

PubMedDate not supplied

Properties of and oxygen binding by albumin-tetraphenylporphyrinatoiron(II) derivative complexes.

A hydrophobic tetraphenylporphyrinatoiron(II) derivative bearing a covalently bound axial imidazole [Fe(II)P] was efficiently and noncovalently bound into human serum albumin (HSA) up to an average of eight Fe(II)P molecules per HSA molecule. The aqueous solutions of the HSA-Fe(II)P complex provided a reversible and relatively stable oxygen adduct under physiological conditions (pH 7.4 and 37 degrees C). The half-life of the oxygen adduct (tau 1/2) was 1 h at 37 degrees C in an air atmosphere. With Fe(II)-TpivPP (the so-called "picket-fence heme") having no axial base, an oxygenated HSA-Fe(II)TpivPP complex was obtained using a 20-fold molar excess of 1,2-dimethylimidazole, but the tau 1/2 was very short (ca. 10 min at 37 degrees C). The oxygen affinity [P 1/2(O2)] and oxygen transporting efficiency (OTE) of HSA-Fe(II)P at 37 degrees C were 30 Torr and 22%, respectively. Furthermore, the oxygen-binding and dissociation rate constants (kon and koff) are extremely high in comparison with those of hemoglobin. The HSA molecule binding eight Fe(II)P molecules can transport about 3.4 mL/dL of oxygen under physiological conditions, corresponding to about 60% of the oxygen transporting amount of human blood.

Blood Substitutes↗

PubMedDate not supplied

Methemoglobin formation in hemoglobin vesicles and reduction by encapsulated thiols.

The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to suppress metHb formation or autoxidation, for the long-term maintenance of the oxygen transporting capability, a series of thiols (cysteine, Cys; glutathione, GSH; homocysteine, Hcy; and acetylcysteine, Acy) were studied as reductants of metHb. Hcy and GSH showed a good suppressive effect on metHb formation, while Cys adversely accelerates the metHb formation at a rate twice that of the Hb solution without any reductants and Acy showed no change. The significant suppression by the coaddition of superoxide dismutase (SOD) and catalase to Cys indicated that Cys was easily oxidized by oxygen and simultaneously generates a large amount of active oxygens. The effective suppression of metHb formation by SOD and catalase was not observed for HbV containing no reductants, indicating that the generation of active oxygens from Hb itself is not significant. The coencapsulation of Hcy with Hb resulted in a low rate of metHb formation in HbV (initial rate, 1%/h) in vitro at an oxygen partial pressure (Po2) of 142 Torr. The rate increased with decreasing Po2, showed a maximum (2.2%/h) around Po2 = 23 Torr, and then decreased to 0%/h at 0 Torr. From these results, it is suggested that the fast metHb formation rate in the blood circulation of Wistar rats injected with 20 vol % of the HbV solution would be mainly caused by the exposure of HbV to the low Po2.

Animals↗

PubMedDate not supplied

Physicochemical properties and O2-coordination structure of human serum albumin incorporating tetrakis(o-pivalamido)phenylporphyrinatoiron(II) derivatives.

Incorporation of tetrakis(o-pivalamido)phenylporphyrinatoiron(II) derivatives with a covalently linked axial imidazole (FeP) into human serum albumin (HSA) provides a new type of artificial hemoprotein (HSA-FeP) that binds and releases dioxygen reversibly under physiological conditions (in aqueous media, pH 7.4, 37 degreesC) and in a fashion similar to hemoglobin and myoglobin. The HSA host adsorbs a maximal eight FeP molecules, and their stepwise equilibrium constants (K1-K8) range from 1.2 x 10(6) to 1.3 x 10(4) M-1. The major binding sites of the synthetic hemes are identical to those of hemin, bilirubin, and long-chain fatty acids. The red-colored solution of HSA-FeP was stored for three months at 4 degreesC and could be kept as a freeze-dried powder for more than six months. The solution properties [[HSA]: 5 wt %, FeP/HSA = 1-8 (mol/mol)] satisfy the physiological requirements for dioxygen infusion for potential clinical use; the specific gravity is 1.013, and the viscosity is 1.1 cP. Mixing the solution with human blood does not induce any coagulation and precipitation. On the basis of the gel permeation chromatography, CD spectroscopy, and IEF measurements, the molecular size, second-order structure, and surface charge distribution of the HSA-FeP conjugate are constant and independent of the binding numbers of heme molecules. Furthermore, the O2-coordination structure of FeP embedded into certain hydrophobic domains of the albumin was confirmed by resonance Raman spectroscopy.

Binding Sites↗

PubMedDate not supplied

Human serum albumin incorporating Tetrakis(o-pivalamido) phenylporphinatoiron(II) derivative as a totally synthetic O2-carrying hemoprotein.

2-[8-{N-(2-Methylimidazolyl)}octanoyloxymethyl]-5,10,15, 20-tetrakis(o-pivalamido)phenylporphinatoiron(II)s (FePs) were incorporated into hydrophobic cavities of recombinant human serum albumin (rHSA), providing a totally synthetic O(2)-carrying hemoprotein (rHSA-FeP). An rHSA host absorbs maximally eight FeP molecules. Solution properties of the obtained albumin hybrid [[rHSA] = 5 wt %; FeP/HSA = 1-8 (mol/mol)] are almost identical to those of the rHSA itself; the specific gravity is 1.013 and the viscosity is 1.1 cP. Circular dichroism spectroscopy and isoelectric focusing measurement revealed that the second-order structure and surface charge distribution of rHSA were always constant independent of the binding numbers of FeP. Hydrophobic interaction is probably a major molecular force of the incorporation of this synthetic heme. rHSA-FeP can bind and release dioxygen reversibly under physiological conditions (in aqueous media, pH 7.3, 37 degrees C) like hemoglobin and myoglobin. Its O(2)-coordination structure was evaluated by resonance Raman spectroscopy. The O(2) rebinding after the laser flash photolysis showed three-phases decay, which were analyzed by triple-exponential kinetics. The O(2)-binding affinity and O(2)-association and -dissociation rate constants of rHSA-FeP satisfy the initial clinical requirements for O(2) infusion as a red cell substitute.

Blood Substitutes↗

PubMedDate not supplied

Exchange transfusion with albumin-heme as an artificial O2-infusion into anesthetized rats: physiological responses, O2-delivery, and reduction of the oxidized hemin sites by red blood cells.

Human serum albumin (HSA) incorporating synthetic hemes, the tetrakis(o-pivalamido)phenylporphinatoiron(II) derivative (FeP), is an artificial hemoprotein (HSA-FeP) which is able to reversibly bind and release dioxygen under physiological conditions (in aqueous media, pH 7.4, 37 degrees C) like hemoglobin and myoglobin. Physiological responses to exchange transfusion with HSA-FeP solution [[HSA], 5 g/dL; FeP/HSA, 4 (mol/mol)] into rats after hemodilution and hemorrhage (Hct, about 10%) has been evaluated. The declined mean arterial pressure (MAP) and blood flow after a 70% exchange with HSA and the further 40% bleeding of blood were significantly recovered up to about 90% of the baseline values by the injection of HSA-FeP. Furthermore, the renal cortical O(2)-tensions and skeletal tissue O(2)-tensions were also increased, indicating the in vivo O(2)-delivery of HSA-FeP. Autoxidation of ferrous Fe(II)P to ferric Fe(III)P was retarded in the blood stream; the half-lifetime of the dioxygenated FeP [tau(1/2)(O(2))] in vivo was 4.1 h [cf. 1.0 h (in vitro)]. It has been found that autooxidized Fe(III)P was certainly reduced in the whole blood suspension. Physiological concentrations of ascorbic acid continuously provided by red blood cells probably rereduces Fe(III)P, leading to the apparent long lifetime of the dioxygenated species of FeP.

Animals↗

PubMedDate not supplied

Synthesis and physicochemical characterization of a series of hemoglobin-based oxygen carriers: objective comparison between cellular and acellular types.

A series of hemoglobin (Hb)-based O(2) carriers, acellular and cellular types, were synthesized and their physicochemical characteristics were compared. The acellular type includes intramolecularly cross-linked Hb (XLHb), polyoxyethylene (POE)-conjugated pyridoxalated Hb (POE-PLP-Hb), hydroxyethylstarch-conjugated Hb (HES-XLHb), and glutaraldehyde-polymerized XLHb (Poly-XLHb). The cellular type is Hb-vesicles (HbV) of which the surface is modified with POE (POE-HbV). Their particle diameters are 7 +/- 2, 22 +/- 2, 47 +/- 17, 68 +/- 24, and 224 +/- 76 nm, respectively, thus all the materials penetrate across membrane filters with 0.4 microm pore size, though only the POE-HbV cannot penetrate across the filter with 0.2 microm pore size. These characteristics of permeability are important to consider an optimal particle size in microcirculation in vivo. POE-PLP-Hb ([Hb] = 5 g/dL) showed viscosity of 6.1 cP at 332 s(-1) and colloid osmotic pressure (COP) of 70.2 Torr, which are beyond the physiological conditions (human blood, viscosity = 3-4 cP, COP = ca. 25 Torr). XLHb and Poly-XLHb showed viscosities of 1.0 and 1.5 cp, respectively, which are significantly lower than that of blood. COP of POE-HbV is regulated to 20 Torr in 5% human serum albumin (HSA). HES-XLHb and POE-HbV/HSA showed comparable viscosity with human blood. Microscopic observation of human red blood cells (RBC) after mixing blood with POE-PLP-Hb or HES-XLHb disclosed aggregates of RBC, a kind of sludge, indicating a strong interaction with RBC, which is anticipated to modify peripheral blood flow in vivo. On the other hand, XLHb and POE-HbV showed no rouleaux or aggregates of RBC. The acellular Hbs (P(50) = 14-32 Torr) have their specific O(2) affinities determined by their structures, while that of the cellular POE-HbV is regulated by coencapsulating an appropriate amount of an allosteric effector (e.g., P(50) = 18, 32 Torr). These differences in physicochemical characteristics between the acellular and cellular types indicate the advantages of the cellular type from the physiological points of view.

Blood Substitutes↗

PubMedDate not supplied

Poly(ethylene glycol)-modification of the phospholipid vesicles by using the spontaneous incorporation of poly(ethylene glycol)-lipid into the vesicles.

The critical micelle concentrations of 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[monomethoxy poly(ethylene glycol) (5000)] (PEG-DPPE) and its distearoyl analogue (PEG-DSPE) were 70 and 9 microM, respectively, in buffer solutions ([Tris] = 20 mM, [NaCl] = 140 mM, pH 7.4) at 37 degrees C. When these PEG-lipid micelle dispersions were mixed with the dispersions of phospholipid vesicles comprised of a C16 membrane, of which the carbon number is 16, or a C18 membrane, the PEG-lipid micelles were dissociated into monomers and then spontaneously incorporated into the surface of the preformed vesicles. The incorporation rates and the enthalpy changes during incorporation were measured with an isothermal titration microcalorimeter. The incorporation rate of PEG-DPPE was faster than that of PEG-DSPE, because the dissociation rate of the PEG-DPPE micelles was faster than that of PEG-DSPE micelles. The incorporation equilibrium constant of PEG-DSPE was larger than that of PEG-DPPE due to its slow dissociation rate from the membrane, caused by the stronger hydrophobic interaction. The combination of PEG-DSPE and the C18 membrane was the most thermodynamically stabilized pair. Furthermore, the dispersion stability of the surface-modified vesicles prepared by this spontaneous incorporation was analyzed by using the critical molecular weight of the polymer for the aggregation of vesicles. The aggregation of the vesicles was successfully supressed with an increase in the molecular weight of the PEG in the PEG-lipid and its incorporation ratio.

Chemical Phenomena↗

PubMedDate not supplied

Poly(ethylene glycol)-conjugation and deoxygenation enable long-term preservation of hemoglobin-vesicles as oxygen carriers in a liquid state.

The stability of hemoglobin vesicles (HbV) as an oxygen infusion was tested during the storage for 1 year at 4, 23, and 40 degrees C. The surface of the HbV was modified with poly(ethylene glycol) (PEG), and the suspension was deoxygenated with nitrogen bubbling. The samples stored at 4 and 23 degrees C showed a stable dispersion state for 1 year, though the sample stored at 40 degrees C showed the precipitation and decomposition of vesicular components, a decrease in pH, and 4% leakage of total Hb after 1 year. The PEG chains on the vesicular surface stabilize the dispersion state and prevent the aggregation and fusion due to their steric hindrance. The original metHb content (ca. 3%) before the preservation gradually decreased to less than 1% in all the samples after 1 month due to the presence of homocysteine inside the vesicles which consumed the residual oxygen and gradually reduced the trace amount of metHb. The rate of metHb formation was strongly dependent on the partial pressure of oxygen, and no increase in metHb formation was observed due to the intrinsic stability of the deoxygenated Hb. Preservation at 4 and 23 degrees C slightly reduced P(50) (increased the oxygen affinity) from 38 Torr to 32 and 31 Torr, respectively. These results indicate the possibility that HbV suspension can be stored at room temperature for at least 1 year.

Chemical Phenomena↗

PubMedDate not supplied

Physical properties of hemoglobin vesicles as red cell substitutes.

Hemoglobin vesicles (HbV) as red cell substitutes were prepared from a purified carbonylhemoglobin (HbCO) solution and a lipid mixture composed of phospholipids, cholesterol, and alpha-tocopherol. The diameter was controlled to 251 +/- 87 nm using an extrusion method; the vesicles penetrated through the membrane filters with regulated pore sizes. After the ligand exchanging reaction (HbCO-->HbO2), the oxygen affinity (P50) of HbV was 32 Torr, which was controlled with the coencapsulation of pyridoxal 5'-phosphate. The rate of metHb formation in HbV was nonenzymatically reduced with the coencapsulation of DL-homocysteine. The Hb concentration of the HbV suspension, which was dispersed in a phosphate buffered saline solution (pH 7.4), was controlled at 10 g/dL. At this concentration, the total lipid concentration was 6.2 g/dL and the viscosity, 2.6 cP (230 s-1), was lower than that of the blood (4.4 cP). The HbV suspension showed a typical non-Newtonian flow for a particle dispersion and agreed well with the Casson model. The viscosity at shear rates lower than 23 s-1 showed a maximum with increasing the mixing ratio of human blood, plasma, or albumin, while no maximum was observed for the mixture with washed red blood cells. The aggregates of HbV are formed by interaction with plasma proteins, including albumin, while the aggregates reversibly dissociate at higher shear rate.

Blood Substitutes↗

PubMedDate not supplied

Characteristics of artificial red cells. Hemoglobin encapsulated in poly-lipid vesicles.

Artificial red cells (ARC) were prepared by encapsulation of purified human Hb with polymerizable phospholipid, 1,2-bis (2,4-octadecadienoyl)-sn-glycero-3-phosphocholine (DODPC). The polymerized lipid bilayer of the ARC produced great physical stability that could not be achieved using a non-polymerizable lipid for encapsulation. ARC showed no change in particle size or distribution or leakage of Hb after repeated freeze thawing (stability test). ARC have also been studied with regard to biocompatibility. The authors' results showed low acute toxicity (> 8000 mg/kg) and adequate blood compatibility. The result of transfusion tests in dogs showed that ARC had sufficient oxygen transporting capabilities.

Animals↗

PubMedDate not supplied

Blood-brain barrier disturbance following localized hyperthermia in rats.

We investigated the morphological effect of hyperthermia on the blood-brain barrier (BBB). The heads of rats were heated locally using flood-lamps. BBB changes were assessed morphologically with horseradish peroxidase (HRP). Histological examinations were carried out 2 and 6 h, 1 and 3 days, and 1 week after the hyperthermia. The acute thermal lesions had three zones, i.e. a necrotic zone, a reactive zone and a permeable zone of viable brain tissue. HRP extravasation was seen in the necrotic zone and the permeable zone. Electron micrographic observation revealed HRP had entered the CNS through damaged endothelial cells and disruption of the tight junctions in the necrotic zone, and through numerous pinocytotic vesicles in the permeable zone. BBB opening to HRP was observed from 6 h to 3 days after hyperthermia.

Animals↗

PubMedDate not supplied

Construction of artificial methemoglobin reduction systems in Hb vesicles.

The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to suppress metHb formation for the long term maintenance of oxygen transporting capability in vivo, thiols (cysteine, Cys; homocysteine, Hcy) were studied as reductants of metHb. Hcy showed a suppressive effect on metHb formation, while Cys adversely accelerates metHb formation at the rate of twice the Hb solution without any reductants. The suppression of Cys-induced metHb formation by the addition of superoxide dismutase (SOD) and catalase indicated that Cys was easily oxidized by oxygen and simultaneously generated a large amount of active oxygens. The rate of metHb formation was influenced by PO2 and pH. Furthermore, the reducing systems (methylene blue (MB), NADH or ascorbic acid) were added to the outer aqueous phase of HbV, and the artificial reduction systems constructed through the bilayer membrane were evaluated.

Blood Substitutes↗

PubMedDate not supplied

Cancer of the oropharynx developed after radiotherapy and chemotherapy for Hodgkin's disease--a case report.

A case of oropharyngeal squamous cell cancer occurring in the radiation field for Hodgkin's disease is reported. The second cancer was diagnosed six years and one month after the patient received 40 Gy/25 fractions. The patient also received salvage chemotherapy two years and six months after the primary radiotherapy. In a review of the world literature, we found 22 cases of head and neck cancer excluding the thyroid gland occurring after radiotherapy alone or radiotherapy combined with chemotherapy for Hodgkin's disease. Although second cancers in the head and neck area after Hodgkin's disease have rarely been reported, those patients cured of the disease should be followed up carefully for a long period of time.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Liposome-embedded-heme as a totally artificial oxygen carrier.

To produce a totally artificial oxygen carrying substance, a synthetic iron-porphyrin (heme) complex that is analogous to the oxygen binding site (protoheme) of hemoglobin was embedded in the phospholipid bilayer of a liposome. The O2 carrying capacity of this liposome-embedded-heme (L/H) was examined by exchange transfusions in beagles. Six beagles were divided into two groups. In Group I, 15 ml/kg of blood was removed, and the same amount of L/H solution was injected intravenously. In Group II, 30 ml/kg of blood was withdrawn, and the same amount of the L/H solution was injected intravenously. The mean L/H concentration in the blood was 0.9 mM in Group I and 1.5 mM in Group II. The oxygen volume transported by 1 mM of the L/H at 1 L/min of cardiac output in Groups I and II were 15 and 17 ml/mM.L.min, respectively. The oxygen volume consumed from 1 mM of the L/H at 1 L/min of cardiac output in Groups I and II were 7.7 and 8.3 ml/mM.L.min, respectively. O2 volume transported by the L/H in Groups I and II were 8 and 15%, respectively. O2 volume consumed from the L/H in Groups I and II were 12 and 24%, respectively. Thus, this liposome-embedded-heme has the ability to combine with oxygen, to transport it to the tissue, and to release it in the tissue. The oxygen volumes transported by and consumed from the L/H were proportional to the L/H concentration in the blood.

Animals↗

PubMedDate not supplied

Evaluation of the capabilities of a hemoglobin vesicle as an artificial oxygen carrier in a rat exchange transfusion model.

Encapsulation of hemoglobin within a liposome is one of the strategies in the development of artificial oxygen carriers. It maintains the oxygen transporting properties of hemoglobin and, at the same time, eliminates the side effects of cell free hemoglobin. Hemoglobin vesicles (HbV) are a type of liposome encapsulated hemoglobin. They have a particle size of approximately 250 nm, a hemoglobin concentration of 10 g/dl, and the oxygen affinity, P50, is regulated to 32 Torr. In this study the authors examined the oxygen transporting capability of HbV in vivo, by performing exchange transfusions in rats. Exchange transfusion (90% of the estimated circulatory volume) with HbV suspended in 5% albumin (containing 160 mEq/L, sodium and 107 mEq/L, chloride) was carried out in male Wistar rats. Mean arterial pressure and heart rate were monitored through the arterial catheter. Arterial blood samples for gas analyses were also obtained from the arterial catheter. Abdominal aortic blood flow was measured by an ultrasonic pulsed Doppler flowmeter as an indicator of cardiac output. The oxygen tension of blood withdrawn from the right atrium was measured as an indicator of mixed venous oxygen tension. These values were employed to calculate oxygen delivery and consumption. Renal cortical and skeletal muscle tissue oxygen tensions were monitored as indicators of tissue perfusion. Five percent albumin and washed rat red blood cells suspended in 5% albumin containing 10 g/dl of hemoglobin; were employed as controls. At the completion of a 90% exchange transfusion, renal cortical and skeletal muscle tissue oxygen tensions, along with oxygen delivery and consumption, were sustained almost equally well with the HbV suspension compared to the washed rat red blood cell suspension, but declined significantly with the albumin suspension. The results indicate that the oxygen transporting capability of HbV was almost equivalent to that of rat red blood cells.

Animals↗