Development and assessment of animal models appropriate for evaluating thrombolytic agents for an early treatment of acute myocardial infarction

1. 心肌梗死动物模型。以哥廷根小型猪、渡边遗传性高脂血症兔和狗为实验对象，建立了具有模拟冠状动脉粥样硬化急性心肌梗死事件病理生理特征的动物模型。痉挛引起的冠状动脉阻塞。在饮食引起的高胆固醇血症的哥廷根小型猪中，通过球囊导管和x射线照射，沿着左冠状动脉反复剥落内皮，产生晚期动脉粥样硬化病变。冠状动脉内注射5 -羟色胺使动脉粥样硬化血管收缩至接近管腔阻塞的水平。快速进展或持续痉挛导致动脉粥样硬化斑块周围的壁内出血。2 .持续性严重痉挛可诱发急性心肌梗死。WHHL兔器质性冠状动脉狭窄。对10 ~ 24月龄的纯合子WHHL兔进行冠状动脉造影，观察冠状动脉狭窄程度及冠状动脉对血清素、组胺、乙酰胆碱、麦角碱等血管活性药物的反应。左、右冠状动脉主干严重狭窄。虽然WHHL兔冠状动脉对血清素和麦角碱的反应比正常日本白兔大，但这些药物干预并没有引起心肌梗死。溶栓治疗对梗死面积和壁运动的影响。研究了重组组织型纤溶酶原激活剂（rt-PA）对闭胸麻醉犬血栓闭塞和溶栓再灌注后梗死面积和/或左室壁运动的影响。rt-PA对梗死面积的有益影响取决于冠状动脉闭塞后的时间间隔，比机械再灌注更有效。溶栓再灌注而非机械再灌注也能改善冠状动脉闭塞后恶化的壁运动。少

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 … More 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