| Project/Area Number |
11694229
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KITABATAKE Akira Hokkaido Univ. Grad. Sch. of Med., Prof., 大学院・医学研究科, 教授 (00124769)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIOKA Mitsuhiro Hokkaido Univ. Grad. Sch. of Med., Prof., 大学院・医学研究科, 教授 (40182729)
FUJI Satoshi Hokkaido Univ., Medical Hospital, Lec., 医学部・附属病院, 講師 (90291228)
SAKUMA Ichiro Hokkaido Univ., Medical Hospital, Lec., 医学部・附属病院, 講師 (40260393)
NAKAI Kunihiko Tohoku Univ. Grad. Sch. of Med., Asso. Prof., 大学院・医学系研究科, 助教授 (00291336)
TOGASHI Hiroko Hokkaido Univ. Grad. Sch. of Med., Asso. Prof., 大学院・医学研究科, 助教授 (20113590)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥16,470,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2001: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2000: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1999: ¥5,300,000 (Direct Cost: ¥5,300,000)
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| Keywords | artificial red blood cell / hemoglobin derivative / nitric oxide / platelet aggregation / platelet adhesion / polyethylene glycol / s-nitrosohemoglobin / perfluorocarbon / セロトニン |
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| Research Abstract |
A cellular hemoglobin (Hb) derivatives developed as red blood cell substitutes (BCSs) are known to be potent vasoconstrictors due to their EDRF/NO scavenging action. We therefore developed polyethylene glycol-modified Hb (PEG-Hb), and further modified it to make s-nitrosylated PEG-Hb (SNO-PEG-Hb) as new candidate oxygen carriers. SNO-PEG-Hb possesses desirable properties as an BCS since it can release NO when tissue is hypoxic and absorbs NO when NO is produced to much. Furthermore, using a new machine we synthesized new emulsion to perfluorochemicals (PFCs) and manufactured several PFC compound as BCSs. We found that after injecting those compound to the rat that SNO-PEG-Hb induced least effects on functions and histology of liver and kidney among three Hb-based oxygen carriers (HBOC)s. Using flowcytemetry effects of HBOCs and PFC compounds on platelets were checked and t was suggested that SNO-PEG-Hb and the new PFC compound have least effects. We tried the application ofHBOCs on acute anemia induced by Babesia infection in the dog. When SNO-PEG-Hb was infused to the brain ischemia-reperfusion model of the rats, it ameliorated their cognitive function. We applied the PFC compound in a dog model of cardiopulmonary bypass operation and it revealed that the compound can save heart from anemia-induced hypoxia. On this occasion simultaneous infusion of albumin was necessary. The ability of PFC compound for the preservation material in liver transplantation was checked. The acute toxicological test of PFCs compounds were performed and it was suggested that the new compound was the safest. Thus, SNO-PEG-Hb and the new PFC compound are expected to be good candidates for clinically available BCSs.
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