【摘要】 目的　制作冬眠心肌的实验性动物模型 ,用于评估各种影像学方法鉴别冬眠心肌的价值及其他相关临床研究。方法　中华小型猪 1 3只 ,全麻下左侧开胸 ,于回旋支近心段放置可进行性缩小的环缩环 ,30～ 50d后行MR电影检查 ,分别在静息及小剂量多巴酚丁胺 (5μg·kg- 1 ·min- 1 )负荷实验下观察左室各节段运动变化并计算其运动积分 ;同时在静息和硝酸异山梨酯负荷下完成核素(99m锝 甲氧基异丁基异腈 ,99mTc MIBI)心肌灌注显像。随后处死动物行电镜取材及氯化三苯基四氮唑 (TTC)染色。结果　实验动物中 3只于术中、术后 3d及 2周死亡 ,其余 1 0只 30d后仍存活。其中 7只动物在静息下MR电影示左室侧壁及后下壁运动丧失或减弱 ,但在小剂量多巴酚丁胺负荷实验时 ,相应的节段运动增强。 6只动物在静息下99mTc MIBI心肌断层显像显示相应的心室节段心肌灌注明显或严重降低 ,应用硝酸异山梨酯介入后心肌显像均有明显改善甚至恢复正常。电镜检查则提示缺血区有不同程度的存活心肌。结论　采用环缩环能够在动物模型中复制低血流灌注的冬眠心肌更多还原

【Abstract】 Objective To establish the chronic low flow myocardial hibernation animal model in pigs, and to assess the diagnostic value for myocardial hibernation by using various imaging methods. Methods A total of 13 miniswine (30-40 kg) were used. All animals underwent general anesthesia and orotracheal intubation while the animals were mechanically ventilated. Under sterile conditions, left ventriculography and coronary angiography were performed by introduction of catheter into the right femoral artery. Further, a left anterolateral thoracotomy was performed in the third intercostal space. The proximal LCX was dissected free to allow placement of an ameroid constrictor. More than 1 month later, left ventriculography and coronary angiography were performed again, followed by cine MRI at rest and during stress with low dose of dobutamine (5 μg·kg -1 ·min -1 ), respectively. Traditional and/or breath hold cine MRI were used to evaluate regional left ventricular wall motion, corresponding to basal, midventricular and apical short axis tomograms. Regional wall motion score index (WMSI) was calculated. At the same time 99m Tc MIBI myocardial SPECT was performed at rest and during nitroglycerin administration, respectively. All animals were finally sacrificed for pathological examination. Triphenyl tetrazolium chloride (TTC) staining was used to assess the myocardial infarction. Electron microscopy was used to identify myocardial cellular changes characteristic of hibernating myocardium. Results Three pigs died during surgery or within two weeks after surgery. One pig died of anesthesia during SPECT examination, 1 pig suffered from aneurysm, and another one pig showed negative findings. The other 7 pigs were found with hypokinetic ( n =4) or akinetic ( n =3) myocardial regions related to stenosed LCX (70%-99%). Resting cine MRI demonstrated decreased regional motion of the lateral and posteroinferior walls (ischemic regions) of the left ventricle ( n =7), compared with the nonischemic anteroseptal regions; but the low dose dobutamine (5 μg·kg -1 ·min -1 ) could recover those hypokinetic or akinetic myocardial regions, characteristic of hibernating myocardium. Resting 99m Tc MIBI myocardial SPECT ( n =6) showed a fixed perfusion defect on the corresponding ischemic areas, which became reversible on the nitrate augmented myocardial perfusion imaging. It also indicated myocardial viability presented at the ischemic areas. TTC staining revealed patchy infarction of the area at risk localized to the endocardial surface ( n =3), and no myocardial infarction ( n =4). Electron microscopy of sections from the hibernating regions revealed loss of contractile materials, increased numbers of small mitochondria, and glycogen accumulation within viable cardiomyocytes, which had been described as hallmarks of hibernating myocardium. Conclusion Chronic low flow myocardial hibernation can be reproduced in an animal model during progressive coronary stenosis caused by ameroid constrictor.更多还原