2004 Fiscal Year Final Research Report Summary
A RESERACH ON DEVELOPMENT AND APPLICATION OF THE CLINICALLY APPRICABLE NEW ARTIFICIALRED BLOOD CELLAND ARTIFICIAL OXYGEN CARRIER
| Project/Area Number |
14370479
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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 | 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 |
SAKUMA Ichiro Hokkaido University Hospital, Lec., 病院, 講師 (40260393)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Satoshi Hokkaido University Hospital, Lect., 病院・講師 (90291228)
YOSHIOKA Mitsuhiro Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (40182729)
TOGASHI Hiroko Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (20113590)
NAKAI Kunihiko Tohoku Univ., Grad.School of Med., Asso.Prof., 大学院・医学系研究科, 助教授 (00291336)
FUKUSHIMA Shoji Kobe Gakuin Univ., Fac.of Pharmaceut.Sci., Asso.Prof., 薬学部, 助教授 (80248103)
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| Project Period (FY) |
2002 – 2004
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| Keywords | ARTIFICIAL RED BLOOD CELL / MODIFIED HEMOGLOBIN / NITRIC OXIDE / PLATELET AGGRIGABILITY / PLATELET ADHESIBILITY / POLYETHYLENE GLYCOL / S-NITROSOHEMOGLOBIN / PERFLUOROCARBON |
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| Research Abstract |
Hemoglobin (Hb)-modified artificial red blood cell has clinically problematic adverse reactions such as blood elevation or activation of platelets and coagulation due to its nitric oxide (NO) quenching. This is derived from absorption of NO released from endothelial cells or nerve endings by heme of Hb molecule. In the present study we developed a new clinically applicable Hb modified molecule in which its SH moiety is s-nitrosylated, thus, can release NO. Also we developed a new perfluorocarbon (PFC) by using a new milking machine, which is melting in a equal sized, stable and with better bioavailability. We checked its bioavailability, clinical availability as an artificial oxygen carrier and artificial organ preserver.
1.We planned the clinical application of NO-PEG-Hb to brain ischemia, and recognized its utility in rat 2VO model. Its mechanism seemed to quench large amount of NO synthesized by iNOS and also NO release from NO-PEG-Hb.
2.To utilized the new PFC as a plasma expander for artificial cardiopulmonary bypass in children, we conduced a simulated experiment using dog and recognized its clinical utility from various cardiac functions, arrhythmias and biochemical parameters.
3.We recognized that the utility of prophylactic application of the new PFC for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.
4.To evaluate effects of various artificial red blood cells on brain ischemia preservation we established a new evaluation method for cognition using the rat.
5.We recognized that the utility of prophylactic application of a liposome-encapsulated hemoglobin, Neo Red Cell (NRC), for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.
6.We recognized the preserving effect of NRC on brain ischemia. by an evaluation method for cognitive function in the rat.
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