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Preclinical Evaluation Tests of Red Cell Substitutes by Microcirculatory Dynamical Analyzes

Research Project

Project/Area Number 07508005
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field Biomedical engineering/Biological material science
Research InstitutionWaseda University

Principal Investigator

TSUCHIDA Eishun  Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (90063461)

Co-Investigator(Kenkyū-buntansha) SUEMATSU Makato  Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (00206385)
ISHIMURA Yuzuru  Keio University, School of Medicine, Professor, 医学部, 教授 (40025599)
KOBAYASHI Kouichi  Keio University, School of Medicine, Professor, 医学部, 教授 (80051704)
TAKEOKA Shinji  Waseda University, School of Science and Engineering, Associate Professor, 理工学部, 助教授 (20222094)
NISHIDE Hiroyuki  Waseda University, School of Science and Engineering, Professor, 理工学部, 教授 (90120930)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥12,000,000 (Direct Cost: ¥12,000,000)
Fiscal Year 1996: ¥12,000,000 (Direct Cost: ¥12,000,000)
Keywordsred cell substitute / hemoglobin / hemoglobin vesicle / microcirculation / animal test / oxygen transport / oxygen dynamics / liver perfusion test / 血流動態 / 肝灌流試験 / リン脂質小胞体
Research Abstract

This research is aimed to evaluate two kinds of blood substitutes in preclinical stage (A.totally synthetic heme and B.hemoglobin (Hb) vesicles) in microcirculation levels, changing the properties of those oxygen carriers and monitoring oxygen distribution in tissues by new apparatus for quantitative analyzes.
In the 90% exchange transfusion tests of Hb vesicles in a 5% albumin solution using rats, stable blood gas parameters and tissue oxygen tension were observed during the entire experiment with almost perfect survival rate, indicating excellent oxygen transporting ability and high safety. The Hb vesicles modified with polyoxyethylene (Mw.5kD) was dispersed in an isotonic albumin solution, and the 90% exchange transfusion ws carried out with hamster whose back was equipped with dorsal skinfold chamber to visualize microvessels in the subcutaneous tissue. Microvascular diameter, blood velocity, functional capillary density, microvascular and interstitial oxygen tensions were measured to evaluate the microcirculatory dynamics of the modified Hb resicles.
Tissue oxygenation of isolated perfused liver was measured quantitatively from the intensity of NADH autofluorescence in periprotal and pericentral regions of the hepatic parenchyma. The excellent properties of cellular Hb compared with acellular one and the effect of surface modification were confirmed from the measurements of microcirculation dynamics.
The totally synthetic heme oxygen carriers also showed oxygen binding ability similar to red blood cells in both in vitro and in vivo measurements. Those fruits will be necessarily to apply those materials in clinical trials in near future.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Hiromi Sakai: "Physical Properties of Hemoglobin Vesicles as Red Cell Substitutes" Biotechnol.Progress. 12. 119-125 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 朴 晟翼: "ポリエチレングリコール型脂質および糖脂質によるヘモグロビン小胞体(HbV)の表面修飾効果" 人工血液. 4. 9-13 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 酒井 宏水: "情報分子(NO,CO)が果たしている生理的役割" 化学. 51. 664-665 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Takeoka: "Layer-Controlled Hemoglobin Vesicles by Interaction of Hemoglobin with a Phosholipid Assembly" Langmuir. 12. 1755-1759 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiromi Sakai: "Functional Evaluation of Hemoglobin- and Lipidheme-vesicles as Red Cell Substitutes" Polym.Adv.Technol.7. 639-644 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yotaro Izumi: "Physiologic Responses to Exchange Transfusion with Hemoglobin Vesicles as an Artificial Oxygen Carrier in Anesthetized Rats : Changes in Mean Arterial Pressure and Renal Cortical Oxygen Tension" Crit.Care Med.24. 1869-1873 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Teruyuki Komatu: "Oxygen Transporting Ability of Lipidheme Microsheres as a Totally Synthetic Red Cell Substitute" Artif.Organs Today. 5. 207-215 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.S.Chen: "Analysis of Facilitated Oxygen Transport in a Liquid Membrane of Hemoglobin" Bull.Chem.Soc.Jpn.69. 255-259 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiromi Sakai: "Surface Modification of Hemoglobin Vesicles with Poly(ethyleneglycol) and Effects on Aggregation,Viscosity,and Blood Flow during 90% Exchange Transfusion in Anethetized Rats" Bioconjugate Chem.8. 23-30 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.I.Park: "O_2 Binding and Dissociation and Ligand Exchange Reaction of O_2 with CO in Polymer Composite Films of Hemoglobin" Polym.Adv.Technol.8. 366-370 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Takeoka: "Reduction of Methemoglobin via Electron Transfer across the Bilayer Membrane of Hb Vesicles" Bull.Chem.Soc.Jpn.70. 1171-1178 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Takeoka: "Construction of Artificial Methemoglobin Reduction Systems in Hb Vesicles" Art.Cells Blood Subs.,and Immob.Biotech.25. 31-41 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroyuki Nishide: "Facilitated Oxygen Transport with Modified and Encapulated Hemoglobins across Non-Flowing Solution Membrane" Art.Cells Blood Subs.,and Immob.Biotech.24. 335-346 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kouichi Kobayashi: "The Oxygen Carrying Capability Of Hemoglobin Vesicles Evaluated In Rat Exchange Transfusion Models" Art.Cells Blood Subs.,and Immob.Biotech.24. 357-366 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Eishun Tsuchida: "Properties of Albumin-Tetraphenylporphynatoiron(II) Derivative Complexes and Their Oxygen-Binding" Bioconjugate Chem.8. 534-538 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Takeoka: "Methemoglobin Formation in Hemoglobin Vesicles and Reduction by Encapsulated Thiols" Bioconjugate Chem.8. 539-544 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yotaro Izumi: "Evaluation of the Capabilities of Hemoglobin Vesicles as an Artificial Oxygen Carrier in a Rat Exchange Transfusion Model" ASAIO J.43. 289-297 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 泉 陽太郎: "出血性ショックモデルを用いた人工酸素運搬体、ヘモグロビン小胞体の酸素運搬能の検討" 人工血液. 5. 18-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiromi Sakai: "Subcutaneous Microvascular Responses to Hemodilution with Red Cell Substitute Consisting of Polyethyleneglycol-modified Vesicles Encapsulating Hemoglobin." J.Biomed.Materials Res.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nobihito Goda: "Distribution of Heme Oxygenase Isoforms In Rat Liver : Topographic Bases for Carbon Monoxide-Mediated Microvascular Relaxation" J.Clin.Invest.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiromi Sakai: "Microvascular Responses to Hemodilution with Hb-vesicles as Red Cell Substitutes : Influences of O_2 Affinity" Am.J.Physiol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiromi Sakai et al.: "Hemoglobin Encapsulation with Polyethyleneglycol-modified and Unmodified Vesicles : Systematic and Microvascular Hemodynamics at 80% Blood Substitution" Current Issues in Blood Substitute Research and Development,1997 (eds.R.M.Winslow et al.),Birkhauser. 151-166 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shinji Takeoka et al.: "Differences in Particle Size and Oxygen-binding Affinity between Crosslinked Hemoglobin and Hemoglobin Vesicle" 1996 Conference on Oxygen Homeostasis and Its Dynamics (ed.Y.Ishimura),Springer-Verlag,Tokyo. 428-433 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Suematsu et al.: "Carbon Monoxide : A Toxic Waste or Endogenous Modulator of Hepatobiliary Function?" 1996 Conference on Oxygen Homeostasis and Its Dynamics (ed.Y.Ishimura),Springer-Verlag,Tokyo. 544-549 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakai, K.Hamada, S.Takeoka, H.Nishide, E.Tsuchida.: "Physical Properties of Hemoglobin Vesicles as Red Cell Substitutes." Biotechnol.Prog.12. 119-125 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Takeoka, T.Ohgushi, K.Terase, T.Ohmori, E.Tsuchida: "Layr-Controlled Hemoglobin Vesicles by Interaction of Hemoglobin with a Phospholipid Assembly." Langmuir. 12. 1755-1759 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakai, K.Hamada, S.Takeoka, H.Nishide, E.Tsuchida: "Functional Evaluation of Hemoglobin- and Lipidheme-vesicles as Red Cell Substitutes." Polym.Adv.Technol.7. 639-644 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Izumi, H.Sakai, K.Hamada, S.Takeoka, Y.Yamahata, R.Kato, H.Nishide, E.Tsuchida, K.Kobayashi: "Physiologic Responses to Exchange Transfusion with Hemoglobin Vesicles as an Artificial Oxygen Carrier in Anesthetized Rats : Changes in Mean Arterial Pressure and Renal Cortical Oxygen Tension." Crit.Care Med.24. 1869-1873 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] T.Komatsu, A.Kuronuma, Y.Muramatsu, H.Nishide, E.Tsuchida, T.Kakizaki, K.Kobayashi: "Oxygen Transporting Ability of Lipidheme Microsheres as a Totally Synthetic Red Cell Substitute." Artif.Organs Today. 5. 207-215 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] X.S.Chen, H.Nishide, E., Tsuchida: "Analysis of Facilitated Oxygen Transport in a Liquid Membrane of Hemoglobin." Bull.Chem.Soc.Jpn.69. 255-259 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakai, S.Takeoka, S.I.Park, T.Kose, H.Nishide, Y.Izumi, A.Yoshizu, K.Kobayashi, E.Tsuchida: "Surface Modification of Hemoglobin Vesicles with Poly (ethyleneglycol) and Effects on Aggregation, Viscosity, and Blood Flow during 90% Exchange Transfusion in Anethetized Rats." Bioconjugate Chem.8. 23-30 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.I.Park, H.Sakai, S.Takeoka, H.Nishide, E.Tsuchida: "O_2 Binding and Dissociation and Ligand Exchange Reaction of O_2 with CO in Polymer Composite Films of Hemoglobin." Polym.Adv.Technol.5. 366-370 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Takeoka, T.Ohgushi, H.Nishide, E.Tsuchida: "Reduction of Methemoglobin via Electron Transfer across the Bilayr Membrane of Hb Vesicles." Bull.Chem.Soc.Jpn.70. 1171-1178 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Takeoka, T.Ohgushi, H.Sakai, T.Kose, H.Nishide, E.Tsuchida: "Construction of Artificial Methemoglobin Reduction Systems in Hb Vesicles." Art.Cells Blood Subs., and Immob.Biotech.25. 31-41 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Nishide, X.S.Chen, E.Tsuchida: "Facilitated Oxygen Transport with Modified and Encapulated Hemoglobins across Non-Flowing Solution Membrane." Art.Cells Blood Subs., and Immob.Biotech.24. 335-346 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Kobayashi, Y.Izumi, A.Yoshizu, H.Horinouchi, S.I.Park, H.Sakai, S.Takeoka, H.Nishide, E.Tsuchida: "The oxygen Carrying Capability Of Hemoglobin Vesicles Evaluated In Rat Exchange Transfusion Models." Art.Cells Blood Subs., and Immob.Biotech.24. 357-366 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Tsuchida, K.Ando, H.Maejima, N.Kawai, T.Komatsu, H.Nishide: "Properties of Albumin-Tetraphenylporphynatoiron (II) Derivative Complexes and Their Oxygen-Binding." Bioconjugate Chem.8. 534-538 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Takeoka, H.Sakai, T.Kose, Y.Mano, Y.Seino, H.Nishide, E.Tsuchida: "Methemoglobin Formation in Hemoglobin Vesicles and Reduction by Encapsulated Thiols." Bioconjugate Chem.8. 539-544 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Izumi, H.Sakai, T.Kose, K.Hamada, S.Takeoka, A.Yoshizu, H.Horinouchi, R.Kato, H.Nishide, E.Tsuchida: "Evaluation of the Capabilities of Hemoglobin Vesicles as an Artificial Oxygen Carrier in a Rat Exchange Transfusion Model." ASAIO J.43. 289-297 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H Sakai, A.G.Tsai, H.Kerger, S.I.Park, S.Takeoka, H.Nishide, E.Tsuchida, M.Intaglietta: "Subcutaneous Microvascular Responses to Hemodilution with Red Cell Substitute Consisting of Polyethyleneglycol-modified Vesicles Encapsulating Hemoglobin." J.Biomed.Materials Res.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Goda, K.Suzuki, M.Naito, S.Takeoka, E.Tsuchida, Y.Ishimura, T.Tamatani, M.Suematsu: "Distribution of Heme Oxygenase Isoforms In Rat Liver : Topographic Bases for Carbon Monoxide-Mediated Microvascular Relaxation." J.Clin.Invest.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakai, A.G.Tsai, R J Rohlfs, S.Takeoka, E.Tsuchida, M.Intaglietta: "Microvascular Responses to Hemodilution with Hb-vesicles as Red Cell Substitutes : Influences of O_2 Affinity." Am.J.Physiol.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Tsuchida: "Overview of Recent Progress in Blood Substitutes." SHOCK From Molecular and Cellular Level to Whole Body (eds.K.Okada et al.) Elsevier Science. 299-303 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Kobayashi, Y.Izumi, T.Yamahata, H.Sakai, S.Takeoka, H.Nishide, E.Tsuchida: "Efficacy of Synthetic Oxygen-Carrying Substances." SHOCK From Molecular and Cellular Level to Whole Body (eds.K.Okada et al.) Elsevier Science. 305-310 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Nishide, E.Tsuchida: "New Preparations and Their Performances in Artificial Red Cells." SHOCK From Molecular and Cellular Level to Whole Body (eds.K.Okada et al.) Elsevier Science. 311-314 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Sakai, A.G.Tsai, M.Intaglietta, E.Tsuchida: "Hemoglobin Encapsulation with Polyethyleneglycol-modified and Unmodified Vesicles : Systematic and Microvascular Hemodynamics at 80% Blood Substitution." Current Issues in Blood Substitute Research and Development, 1997 (eds.R.M.Winslow et al.) Birkhauser. 151-166 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S.Takeoka, Y.Mano, E.Tsuchida: "Differences in Particle Size and Oxygen-binding Affinity between Crosslinked Hemoglobin and Hemoglobin Vesicle." 1996 Conference on Oxygen Homeostasis and Its Dynamics (ed.Y.Ishimura) Springer-Verlag, Tokyo. 433 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] M.Suematsu, T.Sano, S.Takeoka, Y.Wakabayashi, T.Yonetani, E.Tsuchida, Y.Ishimura: "Carbon Monoxide : A Toxic Waste or Endogenous Modulator of Hepatobiliary Function? ." 1996 Conference on Oxygen Homeostasis and Its Dynamics (ed.Y.Ishimura) Springer-Verlag, Tokyo. 549 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 朴晟翼: "ポリエチレングリコール型脂質および糖脂質によるヘモグロビン小胞体の表面修飾効果" 人工血液(日本血液代替物学会誌). 4. 9-14 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shinji Takeoka: "Layer controlled hemoglobin-vesicles by interaction of hemoglobin …" Langmuir. 12. 1755-1759 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiromi Sakai: "Physical properties of hemoglobin vesicles as red cell substitutes" Biotechnol.Progress. 11. 119-125 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiromi Sakai: "Functional evaluation of hemoglobin-and lipidheme-vesicles …" Polym.Adv.Technol.7. 639-644 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yotaro Izumi: "Physiological responses to exchange transfusion with hemoglobin …" Critical Care Medicine. 24. 1869-1873 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiromi Sakai: "Surface-modification of hemoglobin vesicles with …" Bioconjugate Chem.8. 23-30 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yotaro Izumi: "Evaluation of the capabilities of hemoglobin vesicles as …" Am.Soc.Artif.Internal Organs J.43(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shinji Takeoka: "Construction of artificial methemoglobin reduction systems in …" Artif.Cells,Blood Subs.,Immobil.Biotech.25(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shinji Takeoka: "Reduction of methemoglobin via electron transfer across the …" Bull.Chem.Soc.Jpn.70(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Shinji Takeoka: "Methemoglobin formation in hemoglobin vesicles and reduction …" Bioconjugate Chem.8(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ciardelli,Tsuchida,Wohrle(Eds.): "Macromolecule-Metal Complexes" Springer-Verlag(Berlin), 318 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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