1998 Fiscal Year Final Research Report Summary
Development of modified hemoglobin molecules with regulated nitric oxide quenching action and their application for cardiovascular system
| Project/Area Number |
09557125
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SAKURA Ichiro Hokkaido Univ. Sch. Of Med., Assist. Inst. -> 北海道大学, 医学部, 助手 (40260393)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAI Kunihiko Tohoku Univ. Grad. Sch. Of Med. Lec., 大学院・医学系研究科, 講師 (00291336)
KITABATAKE Akira Hokkaido Univ. Sch. Of Med., Pro., 医学部, 教授 (00124769)
YOSHIOKA Mitsuhiro Hokkaido Univ. Sch. Of Med., Pro., 医学部, 教授 (40182729)
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| Project Period (FY) |
1997 – 1998
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| Keywords | artificial red blood cell / modified hemoglobin / artificial oxygen carrier / vascular endothelial cell / nitric oxide / S-nitrosohemoglobin / microdialysis method |
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| Research Abstract |
Artificial red blood cells have long been awaited to be clinically available for the treatment of many kinds of patients because they are free of virus and can be infused to refusers of ordinal blood transfusion. In order to reduce adverse reactions of hemoglobin (Hb)-based oxygen carriers, such as elevation of blood pressure and potentiation of platelet aggregation, induced by their nitric oxide (NO) quenching action, we tried to develop new molecules that would be c1inically usable as artificial red blood cells.
During 1997 to 1999 research project owing to the Grand-in-Aid, we found that 1. The NO sequestrating action of Hb-based molecules is brought about after they penetrate into blood vessels through the gaps between endothelial cells, thus, the bigger the size of Hb-based molecule is, the less the NO sequestration occurs. 2. The size of Hb-based molecules also decides the magnitude of NO sequestration in the rat heart. 3. We then tried to S-nitrosylate the β-chain of Hb molecule and became able to manufacture S-nitroso-Hb (SNO-Hb) of up to 70 % purity. When injected intravenously, SNO-Hb proved to have fewer effects on blood pressure and platelet aggregation compared with stroma-free Hb.
Furthermore, 5. We proved the usefulness of the modalities listed below for the evaluation of biological actions of artificial red blood cells; (1) continuous brain NO measurement with microdialysis connected on line to an HPLC system, (2) ex vivo platelet aggrigometry using laser beam scatter, (3) assessment of cerebral oxygenation and redox behavior of cytochrome oxidase by near-infrared spectroscopy.
Finally, 6. We newly developed a long chain polyethylene glycol-conjugated Hb and started investigating its biological activity.
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Research Products
(30 results)
