Kinetic Studies of Intravascular Thrombus Formation Using Newly Developed Thrombus Model in Microvessels
Project/Area Number |
60480226
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Research Category |
Grant-in-Aid for General Scientific Research (B)
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Allocation Type | Single-year Grants |
Research Field |
Circulatory organs internal medicine
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Research Institution | University of Tsukuba |
Principal Investigator |
OHSHIMA Norio Institute of Basic Medical Sciences, University of Tsukuba, 基礎医学系, 教授 (50015971)
|
Co-Investigator(Kenkyū-buntansha) |
KIKUCHI Yuji do., 基礎医学系, 講師 (20002107)
SATO Madaki do., 基礎医学系, 講師 (30111371)
|
Project Period (FY) |
1985 – 1986
|
Project Status |
Completed (Fiscal Year 1986)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1986: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1985: ¥3,400,000 (Direct Cost: ¥3,400,000)
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Keywords | Fluorescent Dye / Platelet Thrombus / Photochemical Reaction / Active Oxygen / Leucocytes / Microcirculation / Hemodynamics / プロスタグランディン |
Research Abstract |
It was found in our laboratory that the platelet thrombi were inducible in microvessels by the irradiation of exciting light in combination with the intravascular administration of fluorescent dye. We have reported that this new platelet thrombus model is useful for the studies on blood coagulation processes in vivo and the evaluation of newly developed antithrombotic agents. However, the details of the mechanisms are not clear so far. In this research project, the kinetics of the platelet thrombus formation was examined in microvessels of the rat mesentery, using this thrombus formation model. The blood flow velocity began to increase soon after the initiation of thrombus formation and continued to increase progressively with the growth of the thrombus particularly in the radial direction. The velocity precipitously dropped after reaching an almost constant level of stenosis. This critical area stenosis had almost a constant value, i.e., 75-95 % of the lumen area. The other experiments were also carried out to evaluate the antithrombotic effects of a few drugs. The growth of platelet thrombi was inhibited dose-dependently by the administrations of prostaglandins (PGE1, PGD2, PGI2). Since excited colored sensitizers (dyes) are expected to interact with oxygen to produce active oxygens, the effects of active oxygens on the thrombus formation were examined. The scavengers of superoxide radiacal and singlet oxygen had significant effects to prolong the thrombus formation times. Furthermore, from the electron micoscopic observations, the leucocytes adhered to the endothelial cells were supposed to have relevance to the thrombogenesis. It was suggested from these results that the active oxygens produced by photochemical reaction play decisive roles to induce damage of the cell membranes of the endothelium, platelet and/or leucocyte. Due to these damages the platelets seemed to begin to adhere to the endothelium and aggregate each other.
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Report
(1 results)
Research Products
(10 results)