Huwer H, Winning J, Vollmar B, Welter C, Menger M D, Schäfers H J
Department of Thoracic & Cardiovascular Surgery, University of Saarland, Homburg/Saar, Germany.
Comp Med. 2000 Aug;50(4):385-90.
Left ventricular dysfunction following myocardial infarction is the most important predictor of adverse prognosis. Novel treatment options in infarction require an appropriate experimental model with a standardized, hemodynamically relevant myocardial injury. We evaluated a cryoinjury model in rodents that allows quantitative analysis of systolic and diastolic dysfunction.
Anesthetized, orally intubated, and ventilated Lewis rats (n = 12) underwent sternotomy. Myocardial necrosis was induced by use of a standardized cryolesion to the obtuse margin of the left ventricle, freezing for 3 minutes to -160 degrees C. Left ventricular performance was analyzed at day 120 after cryoinjury. Sham-operated animals (n = 10) served as controls.
Cryoinjured animals behaved normally and gained weight up to day 120. Average heart weight of cryoinjured animals significantly exceeded that of controls. Left ventricular systolic pressure and systolic, diastolic, and mean aortic pressures were lower 4 months after cryoinjury, whereas left ventricular end-diastolic pressure was significantly increased. Cryoinjured animals had reduced aortic blood flow, as well as impaired maximal left ventricular dP/dt during aortic occlusion and aortic occlusion-provoked peak systolic pressure. Analysis of maximal rates of isovolumic pressure decrease revealed significant reduction in peak negative dP/dt in cryoinjured animals. Finally, time constants of isovolumic pressure decline were significantly prolonged in cryoinjured animals.
Standardized cryothermia induces a myocardial lesion that results in highly reproducible impairment of left ventricular performance 120 days after cryothermia. The model is ideally suited to test novel therapeutic strategies for myocardial dysfunction.
心肌梗死后左心室功能障碍是不良预后的最重要预测因素。梗死的新型治疗方案需要一个合适的实验模型，该模型具有标准化的、与血流动力学相关的心肌损伤。我们评估了一种啮齿动物冷冻损伤模型，该模型可对收缩和舒张功能障碍进行定量分析。
对麻醉、经口插管并通气的Lewis大鼠（n = 12）进行胸骨切开术。通过对左心室钝缘使用标准化冷冻损伤诱导心肌坏死，冷冻3分钟至-160℃。在冷冻损伤后第120天分析左心室功能。假手术动物（n = 10）作为对照。
冷冻损伤的动物行为正常，直至第120天体重增加。冷冻损伤动物的平均心脏重量显著超过对照组。冷冻损伤4个月后，左心室收缩压以及收缩期、舒张期和平均主动脉压降低，而左心室舒张末期压力显著升高。冷冻损伤的动物主动脉血流量减少，主动脉闭塞期间最大左心室dP/dt以及主动脉闭塞诱发的收缩压峰值受损。等容压力下降最大速率分析显示，冷冻损伤动物的负向dP/dt峰值显著降低。最后，冷冻损伤动物的等容压力下降时间常数显著延长。
标准化低温诱导心肌损伤，导致低温后120天左心室功能出现高度可重复的损害。该模型非常适合测试心肌功能障碍的新型治疗策略。
