Biomedical subjects

Eishun Tsuchida

Publications and source records attributed to Eishun Tsuchida.

At least 37 records · Page 2Linked to original sources

PubMed2004

Circulation kinetics and organ distribution of Hb-vesicles developed as a red blood cell substitute.

Phospholipid vesicles encapsulating concentrated human hemoglobin (Hb-vesicles, HbV), also known as liposomes, have a membrane structure similar to that of red blood cells (RBCs). These vesicles circulate in the bloodstream as an oxygen carrier, and their circulatory half-life times (t(1/2)) and biodistribution are fundamental characteristics required for representation of their efficacy and safety as a RBC substitute. Herein, we report the pharmacokinetics of HbV and empty vesicles (EV) that do not contain Hb, in rats and rabbits to evaluate the potential of HbV as a RBC substitute. The samples were labeled with technetium-99m and then intravenously infused into animals at 14 ml/kg to measure the kinetics of HbV elimination from blood and distribution to the organs. The t(1/2) values were 34.8 and 62.6 h for HbV and 29.3 and 57.3 h for EV in rats and rabbits, respectively. At 48 h after infusion, the liver, bone marrow, and spleen of both rats and rabbits had significant concentrations of HbV and EV, and the percentages of the infused dose in these three organs were closely correlated to the circulatory half-life times in elimination phase (t(1/2beta)). Furthermore, the milligrams of HbV per gram of tissue correlated well between rats and rabbits, suggesting that the balance between organ weight and body weight is a fundamental factor determining the pharmacokinetics of HbV. This factor could be used to estimate the biodistribution and the circulation time of HbV in humans, which is estimated to be equal to that in rabbit.

Algorithms↗

PubMed2004

Synthesis of protoheme IX derivatives with a covalently linked proximal base and their human serum albumin hybrids as artificial hemoprotein.

The simple one-pot reaction of protoporphyrin IX and omega-(N-imidazolyl)alkylamine or O-methyl-L-histidyl-glycine with benzotriazol-1-yl-oxytris(dimethylamino)phosphonium hexafluorophosphate at room temperature produced a series of protoporphyrin IX species with a covalently linked proximal base at the propionate side-chain. The central iron was inserted by the general FeCl2 method, converting the free-base porphyrins to the corresponding protoheme IX derivatives. Mesoporphyrin IX and diacetyldeuteroporphyrin IX analogues were also prepared by the same procedure. The Fe(II) complexes formed dioxygen (O2) adducts in dimethylformamide at 25 degrees C. Some of them were incorporated into the hydrophobic domain of recombinant human serum albumin (rHSA), providing albumin-heme hybrids (rHSA-heme), which can bind and release O2 in aqueous media (pH 7.3, 25 degrees C). The oxidation process of converting the dioxygenated heme in rHSA to the inactive Fe(III) state obeyed first-order kinetics, indicating that the mu-oxo dimer formation was prevented by the immobilization of heme in the albumin scaffold. The rHSA-heme, in which the histidylglycil tail coordinates to the Fe(II) center, showed the most stable O2 adduct complexes.

Dimethylformamide↗

PubMed2004

Physiological capacity of the reticuloendothelial system for the degradation of hemoglobin vesicles (artificial oxygen carriers) after massive intravenous doses by daily repeated infusions for 14 days.

A hemoglobin vesicle (HbV; diameter 252 +/- 53 nm) or liposome-encapsulated Hb is an artificial oxygen carrier developed for use as a transfusion alternative, and its oxygen-transporting capacity has been well characterized, although critical physiological compartments for the Hb degradation after a massive infusion of HbV and the safety outcome remain unknown. In this study, we aimed to examine the compartments for its degradation by daily repeated infusions (DRI) of HbV, focusing on its influence on the reticuloendothelial system (RES). Male Wistar rats intravenously received the HbV suspension at 10 ml/kg/day for 14 consecutive days. The cumulative infusion volume (140 ml/kg) was equal to 2.5 times the whole blood volume (56 ml/kg). The animals tolerated the DRI well and survived, and body weights continuously increased. One day after DRI, hepatosplenomegaly occurred significantly through the accumulation of large amounts of HbV. Plasma clinical chemistry was overall normal, except for a transient elevation of lipid components derived from HbV. These symptoms subsided 14 days after DRI. Hemosiderin deposition and up-regulation of heme oxygenase-1 coincided in the liver and spleen but were not evident in the parenchyma of these organs. Furthermore, the plasma iron and bilirubin levels remained unchanged, suggesting that the heme-degrading capacity of the RES did not surpass the ability to eliminate bilirubin. In conclusion, phospholipid vesicles for the encapsulation of Hb would be beneficial for heme detoxification through their preferential delivery to the RES, a physiological compartment for degradation of senescent RBCs, even at doses greater than putative clinical doses.

Animals↗

PubMed2004

Detection of lipopolysaccharide in hemoglobin-vesicles by Limulus amebocyte lysate test with kinetic-turbidimetric gel clotting analysis and pretreatment of surfactant.

A method to quantitatively measure the bacterial endotoxin content (lipopolysaccharide, LPS) in phospholipid vesicles or liposomes is necessary because the conventional Limulus amebocyte lysate (LAL) test does not provide an accurate measurement due to the hydrophobic interaction of LPS and vesicles that shields the activity of LPS to clot the LAL coagulant. This interference was evident from isothermal titration calorimetry results in our study that clearly demonstrated the insertion of the LPS molecule into the phospholipid bilayer membrane. Hemoglobin-vesicles (HbVs; particle diameter = 251 +/- 80 nm; [Hb] = 10 g/dL) are artificial oxygen carriers encapsulating a conc. Hb solution in phospholipid vesicles, and their oxygen transporting ability has been extensively studied. To accurately measure the LPS content in the HbV suspension, we tested the solubilization of HbV with deca(oxyethylene) dodecyl ether (C(12)E(10)), used to release the LPS entrapped in the vesicles, as a pretreatment for the succeeding LAL assay of the kinetic-turbidimetric gel clotting (detecting wavelength, 660 nm). The C(12)E(10) surfactant interferes with the gel clotting in a concentration-dependent manner, and the optimal condition was determined in terms of minimizing the dilution factor and C(12)E(10) concentration. We clarified the condition that allowed the measurement of LPS at >0.1 endotoxin units (EU)/mL in the HbV suspension. Moreover, the utilization of histidine-immobilized agarose gel effectively concentrated the trace amount of LPS from the C(12)E(10)-solubilized HbV solution and washed out C(12)E(10) as an inhibitory element. The LAL assay with the LPS-adsorbed gel resulted in the detection limit of 0.0025 EU/mL. Pretreatment with C(12)E(10) would be applicable not only to HbVs but also to other drug delivery systems using phospholipid vesicles encapsulating or incorporating functional molecules.

Animals↗

PubMed2004

Metabolism of hemoglobin-vesicles (artificial oxygen carriers) and their influence on organ functions in a rat model.

Phospholipid vesicles encapsulating Hb (Hb-vesicles: HbV) have been developed for use as artificial O(2) carriers (250 nm phi). As one of the safety evaluations, we analyzed the influence of HbV on the organ functions by laboratory tests of plasma on a total of 29 analytes. The HbV suspension ([Hb]=10 g/dl) was intravenously infused into male Wistar rats (20 ml/kg; whole blood = 56 ml/kg). The blood was withdrawn at 8h, and 1, 2, 3, and 7 days after infusion, and the plasma was ultracentrifuged to remove HbV in order to avoid its interference effect on the analytes. Enzyme concentrations, AST, ALT, ALP, and LAP showed significant, but minor changes, and did not show a sign of a deteriorative damage to the liver that was one of the main organs for the HbV entrapment and the succeeding metabolism. The amylase and lipase activities showed reversible changes, however, there was no morphological changes in pancreas. Plasma bilirubin and iron did not increase in spite of the fact that a large amount of Hb was metabolized in the macrophages. Cholesterols, phospholipids, and beta-lipoprotein transiently increased showing the maximum at 1 or 2 days, and returned to the control level at 7 days. They should be derived from the membrane components of HbV that are liberated from macrophages entrapping HbV. Together with the previous report of the prompt metabolism of HbV in the reticuloendothelial system by histopathological examination, it can be concluded that HbV infusion transiently modified the values of the analytes without any irreversible damage to the corresponding organs at the bolus infusion rate of 20 ml/kg.

Animals↗

PubMed2004

Hemoglobin-vesicles suspended in recombinant human serum albumin for resuscitation from hemorrhagic shock in anesthetized rats.

OBJECTIVE: Hemoglobin-vesicle (HbV) has been developed to provide oxygen-carrying ability to plasma expanders. Its ability to restore the systemic condition after hemorrhagic shock was evaluated in anesthetized Wistar rats for 6 hrs after resuscitation. The HbV was suspended in 5 g/dL recombinant human serum albumin (HbV/rHSA) at an Hb concentration of 8.6 g/dL. DESIGN: Prospective, randomized, controlled trial. SETTING: Department of Surgery, School of Medicine, Keio University. SUBJECTS: Forty male Wistar rats. INTERVENTIONS: The rats were anesthetized with 1.5% sevoflurane inhalation throughout the experiment. Polyethylene catheters were introduced through the right jugular vein into the right atrium for infusion and into the right common carotid artery for blood withdrawal and mean arterial pressure monitoring. MEASUREMENTS AND MAIN RESULTS: Shock was induced by 50% blood withdrawal. The rats showed hypotension (mean arterial pressure = 32 +/- 10 mm Hg) and significant metabolic acidosis and hyperventilation. After 15 mins, they received HbV/rHSA, shed autologous blood (SAB), washed homologous red blood cells (wRBC) suspended in rHSA (wRBC/rHSA, [Hb] = 8.6 g/dL), or rHSA alone. The HbV/rHSA group restored mean arterial pressure to 93 +/- 8 mm Hg at 1 hr, similar to the SAB group (92 +/- 9 mm Hg), which was significantly higher compared with the rHSA (74 +/- 9 mm Hg) and wRBC/rHSA (79 +/- 8 mm Hg) groups. There was no remarkable difference in the blood gas variables between the resuscitated groups; however, two of eight rats in the rHSA group died before 6 hrs. After 6 hrs, the rHSA group showed significant ischemic changes in the right cerebral hemisphere relating to the ligation of the right carotid artery followed by cannulation, whereas the HbV/rHSA, SAB, and wRBC/rHSA groups showed less changes. CONCLUSIONS: HbV suspended in recombinant human serum albumin provides restoration from hemorrhagic shock that is comparable with that using shed autologous blood.

Anesthesia↗

PubMed2003

Function of fibrinogen gamma-chain dodecapeptide-conjugated latex beads under flow.

In order to perform a fundamental study of platelet substitutes, novel particles that bound to activated platelets were prepared using two oligopeptides conjugated to latex beads. The oligopeptides were CHHLGGAKQAGDV (H12), which is a fibrinogen gamma-chain carboxy-terminal sequence (gamma 400-411), and CGGRGDF (RGD), which contains a fibrinogen alpha-chain sequence (alpha 95-98 RGDF). Both peptides contained an additional amino-terminal cysteine to enable conjugation. Human serum albumin was adsorbed onto the surface of latex beads (average diameter 1microm) and pyridyldisulfide groups were chemically introduced into the adsorbed protein. H12 or RGD peptides were then chemically linked to the modified surface protein via disulfide linkages. H12- or RGD-conjugated latex beads prepared in this way enhanced the in vitro thrombus formation of activated platelets on collagen-immobilized plates under flowing thrombocytopenic-imitation blood. Based on the result of flow cytometric analyses of agglutination, PAC-1 binding, antiP-selectin antibody binding, and annexin V binding, the H12-conjugated latex beads showed minimal interaction with non-activated platelets. These results indicate the excellent potential of H12-conjugated particles as a candidate for a platelet substitute.

Biomimetic Materials↗

PubMed2003

Molecular energy and electron transfer assemblies made of self-organized lipid-porphyrin bilayer vesicles.

Novel molecular energy and electron transfer assemblies in vesicular form, which are made of self-organized amphiphilic porphyrins bearing phospholipid-like substituents (lipid-porphyrins), have been photochemically characterized. Tetraphenylporphyrin (TPP) derivatives with four dialkylphosphocholine groups [free-base (1 a), Zn(2+) complex (1 b), and Fe(3+) complex (1 c)] are spontaneously associated in water to form spherical unilamellar vesicles with a diameter of 100-150 nm. Exciton calculations based on the bilayered sheet model of 1 b, which has a porphyrin packing similar to that seen in the triclinic unit cell of the Zn(2+)TPP crystals, reproduced the Soret band bathochromic shift appearing in the aqueous solution of 1 b well. The UV/Vis absorption spectrum of the 1 a/1 b hybrid vesicles (molar ratio: 1/1) showed no electronic interaction between the two porphyrin chromophores in the ground state, but efficient intermolecular singlet-singlet energy transfer took place from the excited 1 b donors to the 1 a acceptor within the vesicle. Near-field scanning optical microspectroscopy of the 1 a/1 b vesicles on a graphite surface also showed only free-base porphyrin fluorescence. The efficiency of the energy transfer was 0.81 and the rate constant was 3.1 x 10(9) s(-1). On the other hand, protoporphyrin IX bearing two alkylphosphocholine propionates (2) was incorporated into the 1 a or 1 c bilayer vesicles (ca. 100 nm phi, molar ratio: 1 a/2 or 1 c/2=10). The UV/Vis absorption spectrum showed that 2 was successfully anchored into the fluid alkylene region of the membrane without stacking. Photoirradiation (lambda(ex): 390 nm) of the 1 c/2 vesicles in the presence of triethanolamine led a vectorial electron transfer from the outer aqueous phase to the membrane center, which allowed reduction of the ferric ion of the Fe(3+)TPP platform.

Electron Transport↗

PubMed2003

Compatibility in vitro of albumin-heme (O(2) carrier) with blood cell components.

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.

Animals↗

PubMed2003

O2 release from Hb vesicles evaluated using an artificial, narrow O2-permeable tube: comparison with RBCs and acellular Hbs.

A phospholipid vesicle that encapsulates a concentrated hemoglobin (Hb) solution and pyridoxal 5'-phosphate as an allosteric effector [Hb vesicle (HbV) diameter, 250 nm] has been developed to provide an O2 carrying ability to plasma expanders. The O2 release from flowing HbVs was examined using an O2-permeable, fluorinated ethylenepropylene copolymer tube (inner diameter, 28 microm) exposed to a deoxygenated environment. Measurement of O2 release was performed using an apparatus that consisted of an inverted microscope and a scanning-grating spectrophotometer with a photon-count detector, and the rate of O2 release was determined based on the visible absorption spectrum in the Q band of Hb. HbVs and fresh human red blood cells (RBCs) were mixed in various volume ratios at a Hb concentration of 10 g/dl in isotonic saline that contained 5 g/dl albumin, and the suspension was perfused at the centerline flow velocity of 1 mm/s through the narrow tube. The mixtures of acellular Hb solution and RBCs were also tested. Because HbVs were homogeneously dispersed in the albumin solution, increasing the volume of the HbV suspension resulted in a thicker marginal RBC-free layer. Irrespective of the mixing ratio, the rate of O2 release from the HbV/RBC mixtures was similar to that of RBCs alone. On the other hand, the addition of 50 vol% of acellular Hb solution to RBCs significantly enhanced the rate of deoxygenation. This outstanding difference in the rate of O2 release between the HbV suspension and the acellular Hb solution should mainly be due to the difference in the particle size (250 vs. 7 nm) that affects their diffusion for the facilitated O2 transport.

Allosteric Regulation↗

PubMed2003

Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.

BACKGROUND: Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. RESULTS: We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. CONCLUSION: The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties.

Binding Sites↗

PubMed2003

Hemostatic effects of polymerized albumin particles bearing rGPIa/IIa in thrombocytopenic mice.

The recombinant fragment of the platelet membrane glycoprotein Ia/IIa (rGPIa/IIa) was conjugated to the polymerized albumin particles (polyAlb) with the average diameter of 180 nm. The intravenous administration of rGPIa/IIa-polyAlb to thrombocytopenic mice ([platelet] = 2.1+/-0.3 x 10(5) particles/ microL) with three doses of ca. 2.4 x 10(10), 7.2 x 10(10), and 2.4 x 10(11)particles/kg, respectively, significantly reduced their bleeding time to 426+/-71, 378+/-101, and 337+/-46 s, respectively, whereas that of the control groups (PBS) was 730+/-198 s. The injection of rGPIa/IIa-polyAlb (2.4 x 10(11)particles/kg) was approximately equal to the effect of the injection of the mouse platelets at a dose of 2.0 x 10(10) particles/kg. It was confirmed that rGPIa/IIa-polyAlb had a recognition ability against collagen and could contribute to the hemostasis in the thrombocytopenic mice as a platelet substitute.

Animals↗

PubMed2003

The first oxovanadium ring in [[O[double bond]V(salen)]2(mu-F)][VO(salen)][BF4].(CH2Cl2)x crystals.

The crystal structure of [{O=VV(salen)}2(mu-F)][VIVO(salen)][BF4].(CH2Cl2)x revealed a hollow cavity with a diameter of 5.3 A that penetrates through the crystal, and a remarkable cyclic chain of the [VO(salen)] unit, a motif that has never been fashioned from oxometal building blocks. These features endow the crystal with a molecular sievelike property for the rapid, reversible, and size-selective absorption of guest CH2Cl2 molecules.

Journal Article↗

PubMed2003

Improved oxygenation in ischemic hamster flap tissue is correlated with increasing hemodilution with Hb vesicles and their O2 affinity.

The aim of this study was to test the influence of oxygen affinity of Hb vesicles (HbVs) and level of blood exchange on the oxygenation in collateralized, ischemic, and hypoxic hamster flap tissue during normovolemic hemodilution. Microhemodynamics were investigated with intravital microscopy. Tissue Po2 was measured with Clark-type microprobes. HbVs with a P50 of 15 mmHg (HbV15) and 30 mmHg (HbV30) were suspended in 6% Dextran 70 (Dx70). The Hb concentration of the solutions was 7.5 g/dl. A stepwise replacement of 15%, 30%, and 50% of total blood volume was performed, which resulted in a gradual decrease in total Hb concentration. In the ischemic tissue, hemodilution led to an increase in microvascular blood flow to maximally 141-166% of baseline in all groups (median; P < 0.01 vs. baseline, not significant between groups). Oxygen tension was transiently raised to 121 +/- 17% after the 30% blood exchange with Dx70 (P < 0.05), whereas it was increased after each step of hemodilution with HbV15-Dx70 and HbV30-Dx70, reaching 217 +/- 67% (P < 0.01) and 164 +/- 33% (P < 0.01 vs. baseline and other groups), respectively, after the 50% blood exchange. We conclude that despite a decrease in total Hb concentration, the oxygenation in the ischemic, hypoxic tissue could be improved with increasing blood exchange with HbV solutions. Furthermore, better oxygenation was obtained with the left-shifted HbVs.

Animals↗

PubMed2003

Coordination of BF(4)(-) to oxovanadium(V) complexes, evidenced by the redox potential of oxovanadium(IV/V) couples in CH(2)Cl(2).

The oxidation of oxovanadium(IV) complexes [LV(IV)O] (L = tetradentate Schiff-base ligands such as N,N'-ethylenebis(salicylideneaminate)(2-) (salen) and N,N'-2,2-dimethylpropylenebis(salicylideneaminate)(2-) (salpn)) to [LV(V)O](+), believed to be responsible for the voltammetric response near 0.6 V vs Ag/AgCl in CH(2)Cl(2) in the presence of tetrabutylammonium tetrafluoroborate as a supporting electrolyte, is in fact coupled to a homogeneous process where [LVO](+) coordinates BF(4)(-) to form a neutral complex formulated as [LVOBF(4)]. The formation constants for [VO(salen)BF(4)] and [VO(salpn)BF(4)] are evaluated to be K(salen)(-)(1) = 1.1 x 10(2) M(-)(1) and K(salpn)(-)(1) = 1.4 x 10 M(-)(1), respectively. Crystal structure of [VO(salen)BF(4)] reveals that one of the fluorine atoms in BF(4)(-) is so close to the vanadium(V) atom as to be practically bound in the solid state.

Journal Article↗

PubMed2003

Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging.

The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.

Anesthesia↗

PubMed2003

Normovolemic hemodilution with Hb vesicle solution attenuates hypoxia in ischemic hamster flap tissue.

The aim of this study was to test whether oxygenation in acutely ischemic, collateralized tissue may be improved by normovolemic hemodilution with a solution containing liposome-encapsulated human Hb (HbV). A skin flap model in anesthetized hamsters was used, which consisted of two parts receiving either anatomic or collateral perfusion. Microhemodynamics were investigated with intravital microscopy. Partial tissue oxygen tension was measured with a Clark-type microprobe. Hemodilution was obtained by exchanging 50% of the total blood volume with HbV suspended in 8% human serum albumin (HSA8) or 6% Dextran 70 (Dx70). The size of the vesicles was 276 nm, the P(50) was 22 mmHg, and the Hb concentration of the solutions was 7.5 g/dl. Colloid osmotic pressure and viscosity were 49.9 mmHg and 8.7 cP for HbV-Dx70 and 40.0 mmHg and 2.9 cP for HbV-HSA8, respectively. Hemodilution with HbV-Dx70 led to an increase in microvascular blood flow in the ischemic microvessels to maximally 158% (median, P < 0.01), whereas blood flow remained virtually unchanged after hemodilution with HbV-HSA8. In the ischemic tissue, oxygen tension was improved from 11.9 to 17.0 mmHg (P < 0.01) after hemodilution with HbV-Dx70 but remained virtually unchanged after hemodilution with HbV-HSA8. Our study suggests that the oxygenation in acutely ischemic, collateralized tissue may be improved by normovolemic hemodilution with HbV suspended in Dx70. The effect was achieved by an increase in microcirculatory blood flow related to the rheological properties of the suspending medium.

Animals↗

PubMed2003

Meso-tetrakis[o-(N-methyl)pyridinium]porphyrin ensembles with axially coordinated cyclodextrin-penetrating phenethylimidazole: reversible dioxygen-binding in aqueous DMF solution.

alpha-Cyclodextrin (alpha CD)-penetrating 2-methyl-1-phenethylimidazole coordinates to the zinc(II) and iron(II) complexes of meso-tetrakis[o-(N-methyl)pyridinium] porphyrinate, giving non-covalently linked alpha CD-porphyrin ensembles; the iron(II) complex can reversibly bind and release dioxygen in aqueous DMF solution.

Journal Article↗