| Project/Area Number |
14370365
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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 |
General surgery
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| Research Institution | Tokai University |
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Principal Investigator |
KAWAGUCHI Akira Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (30195052)
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| Co-Investigator(Kenkyū-buntansha) |
KISE Yoshifumi Tokai University, School of Medicine, Assistant Researcher, 医学部, 助手 (00276825)
TANABE Teruhisa Tokai University, School of Medicine, Professor, 医学部, 教授 (10119688)
HAIHA Munetaka Tokai University, School of Medicine, Professor, 医学部, 教授 (20208408)
KUWAHIRA Ichiro Tokai University, School of Medicine, Assistant Professor, 医学部, 助教授 (60186567)
MURAYAMA Chieko Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (50307295)
猪口 貞樹 東海大学, 医学部, 教授 (60160008)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥10,600,000 (Direct Cost: ¥10,600,000)
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| Keywords | Liposome-encapsulated hemoglobin / oxygenation / microcirculation / ischemia / myocardial ischemia / infarction / cerebral ischemia / reperfusion / radiotherapy |
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| Research Abstract |
Background. We tested a hypothesis that an ultra-small (200 nm) liposome-encapsulated-hemoglobin (LEH) with a high oxygen affinity (P_<50>=10 mmHg) may limit ischemia damages in circulatory insufficiency such as cerebral ischemia (CI), myocardial ischemia (MI) and potentiate tumor radiotherapy.
Cerabral Ischemia. LEH was intravenously infused 1% of body weight 5 minutes before and after occlusion of the right middle cerebral artery in rats. Severity of edema was compared with CI rats without treatment 24-hour later on T2 weighed relative signal strength obtained with MRI system at cortex1 striatum, hippocampus and pyriform lobe. LEH was effective in reducing brain edema in all areas except in pyriform lobe in LEH-treated rats. LEH was effective in reducing brain edema before as well as after CI in the rat.
Myocardial Ischemia. Pressure-volume loops were analyzed 10 and 40 minutes after occlusion of the left anterior descending artery and 20 minutes after reperfusion in rats pretreated with LEH or saline of 1% body-weight. Although end-diastolic or end-systolic left ventricular volumes were not different, stroke volume, end-diastolic pressure and ejection fraction were significantly preserved in LEH-treated rats.
Neoplasm. NRC (0.5%, 1%, 2% of body weight) was intravenously infused 30, 60, 90 and 120 minutes before radiation therapy on implanted squamous cell carcinoma in mice. NRC was most effective when 1% NRC infusion 30 minutes prior to radiation, which prolonged 5-times tumor -growth time from 20 days (no treatment) to 26 days.
Conclusion. High-O_2-affinity LEH was effective to ameliorate cerebral and myocardial ischemia and potentiate radiation therapy against tumor growth. Optimal dose, timing and O_2-affinity need to be further defined.
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