1989 Fiscal Year Final Research Report Summary
Development and assessment of animal models appropriate for evaluating thrombolytic agents for an early treatment of acute myocardial infarction
| Project/Area Number |
63870039
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Research Institute of Angiocardiology and Cardiovascular Clinic Faculty of Medicine, Kyushu University |
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Principal Investigator |
NAKAMURA Motoomi KYUSHU UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (60037322)
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| Co-Investigator(Kenkyū-buntansha) |
居石 克夫 九州大学, 医学部, 教授 (70108710)
SUNAGAWA Kenji KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 助手 (50163043)
TOMOIKE Hitonobu KYUSHU UNIVERSITY, MEDICINE, LECTURER, 医学部, 講師 (90112333)
KANAIDE Hideo KYUSHU UNIVERSITY, MEDICINE, PROFESSOR, 医学部, 教授 (80038851)
TAKESHITA Akira KYUSHU UNIVERSITY, MEDICINE, ASSO. PROF., 医学部, 助教授 (30038814)
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| Project Period (FY) |
1988 – 1989
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| Keywords | THROMBOLYSIS / MYOCARDIAL INFARCTION / rt-PA / ANIMAL MODEL / ARTERIOSCLEROSIS / INTRAMURAL HEMORRHAGE / STUNNED MYOCARDIUM / WHHL RABBIT |
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| Research Abstract |
1. Animal model of myocardial infarction. Animal models with pathophysiological features mimicking to events in acute myocardial infarction in patients with coronary atheroselerosis were developed in Gottingen miniature pigs, WHHL (Watanabe Hereditable Hyperlipidemic) rabbits and dogs.
2. Induction of coronary obstruction due to spasm. Advanced atherosclerotic lesions were produced along the left coronary artery following repeated endothelial denudation by a balloon catheter and X-ray irradiation in Gottingen miniature pigs under diet-induced hypercholesterolemia. Intracoronary injection of serotonin constricted the atherosclerotic vessel near to the level of luminal obstruction. Rapid progression or sustained duration of spasm resulted in intramural hemorrhage around the atheromatous plaque. Acute myocardial infarction was induced in cases with persistent severe spasm.
3. Organic coronary stenosis in WHHL rabbits. Coronary angiography was performed in homozygous WHHL rabbits 10-24 month
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s old to assess the level of coronary stenosis and the responses of the coronary artery to vasoactive agents, including serotonin, histamine, acetylcholine and ergonovine. Severe coronary stenosis was noted at the main trunk of the right and left coronary arteries. Although responses of the coronary arteries in WHHL rabbits to serotonin and ergonovine were larger than that of normal Japanese white rabbits, myocardial infarction was not provoked by these pharmacological interventions.
4. Effects of thrombolytic therapy on infarct size and wall motion. Effects of recombinant tissue-type plasminogen activator (rt-PA) on infarct size and/or left ventricular wall motion following thrombotic occlusion and thrombolytic reperfusion were studied in anesthesized closed chest dogs. Beneficial effects of rt-PA on infarct size depended on the interval after coronary occlusion and was more efficient than the mechanical reperfusion. Thrombolytic but not mechanical reperfusion also improved wall motion which had deteriorated after coronary occlusion. Less
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Research Products
(15 results)
