| Project/Area Number |
15590191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Showa University |
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Principal Investigator |
HOMMA Ikuo Showa Univ, Dept of Physiology, Professor, 医学部, 教授 (20057079)
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| Co-Investigator(Kenkyū-buntansha) |
IWASE Michiko Showa Univ, Dept of Physiol, Lecturer, 医学部, 講師 (80119164)
KANAMARU Mitsuko Showa Univ, Dept of Physiol, Research Associate, 医学部, 助手 (40255716)
SHIRASAWA Takuji Tokyo Metropolitan Institute of Gerontology, Dept of Molecular Gerontology, Associate Professor, 分子老化研究グループ, 副参事研究員 (80226323)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Hemoglobin / Presbyterian mutation / ventilation / O_2 consumption / Ptissue O_2 / hypoxia / chronic respiratory failure / プレスバイタリアン / 異常ヘモグロビン / 高炭酸ガス / 炭酸ガス排出量 / 低酸素血症 |
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| Research Abstract |
Patients with chronic respiratory failure because of lung diseases show tissue hypoxia. O2 therapy can approve tissue hypoxia, but largely restricts a patient's daily life. Shirasawa et al. generated model mice that carry low affinity hemoglobin with Presbyterian mutation in the (β-globin gene. Since the low affinity Hb is advantageous for the tissue oxygenation, we examined the respiratory characteristics of model mice with mutation of Presbyterian Hb in vivo. Ptissue O_2 was higher in Presbyterian mice than in wild type mice under hypoxic conditions, showing that more oxygen was released in the peripheral tissues. In the Presbyterian mice, O_2 consumption was significantly higher than wild type mice during normoxia and mild hypoxia. Hypoxic and hypercapnic ventilatory responses were blunted in the Presbyterian mice compared with that in the wild type mice. Results suggest that recombinant Hbs or erythrocytes containing mutant Hbs could improve the symptoms of chronic respiratory failure when transfused or introduced by gene therapy. However, chronically enhanced O_2 delivery to peripheral tissues can reduce ventilation during acute hypercapnic and hypoxic exposures. Further animal experiments should be explored to determine the clinical applications of Presbyterian mice.
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