Closed-chest small animal model to study myocardial infarction in an MRI environment in real time
Closed-chest small animal model to study myocardial infarction in an MRI environment in real time
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DOI：
10.1007/s10554-014-0539-0
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发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Messroghli, Daniel R.
中科院分区：
文献类型：
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作者：
H-Ici, Darach O.;Jeuthe, Sarah;Messroghli, Daniel R.
目前用于心肌缺血/再灌注效应的真实的时间研究的模型具有主要的局限性和混杂因素。混杂因素包括开胸手术的手术压力和开胸的异常生理。重新定位动物的需要干扰了与缺血相关的早期变化的研究。因此，很难直接比较缺血前和缺血后的图像。我们开发了一种新的“闭胸”缺血/再灌注模型来克服这些问题。开胸后，我们将球囊封堵器缝合到雄性Sprague-Dawley大鼠的左冠状动脉。我们使用目视检查和ECG来评估手术时通过球囊的短暂充气和放气成功闭塞和再灌注冠状动脉。然后将管放置在皮肤下并闭合切口。恢复期（5-10天）后，动物接受MRI。我们对左心室功能进行了基线评估，并在冠状动脉闭塞15分钟期间和重新开放冠状动脉后60分钟再灌注期间重复LV测量。44只动物中有40只成功置入封堵器。4例出现术中并发症; 2例大面积心肌梗死，2例晚期出血。6例患者在术后一周内死亡，[4例猝死（推测为猝死），1例前壁梗死，1例败血症]。电影MRI显示其余34只动物中有31只出现局部运动功能减退。左心室射血分数（EF）从基线时的63 +/-A7%降至冠状动脉闭塞期间的49 +/-A9%。左室射血分数恢复至61 +/- A 2%。心脏染色的风险区域为41.9 +/- A 15.8%。该方法允许在冠状动脉闭塞之前、期间和之后研究缺血/再灌注的影响。当动物在MRI中时可能引起缺血。这种新的和临床相关的小动物模型是一个有价值的工具，实时研究单次或重复冠状动脉闭塞/再灌注的影响。
Current models for real time study of the effects of myocardial ischemia/reperfusion have major limitations and confounders. Confounders include the surgical stresses of a thoracotomy and abnormal physiology of an open chest. The need to reposition the animal interferes with the study of the early changes associated with ischemia. Direct comparison of pre-ischemia and post-ischemia images is then difficult. We developed a novel "closed chest" model of ischemia/reperfusion to overcome these issues. Following thoracotomy, we sutured a balloon occluder to the left coronary artery of male Sprague-Dawley rats. We used both visual inspection and ECG to assess for successful occlusion and reperfusion of the coronary artery at the time of operation by brief inflation and deflation of the balloon. The tubing was then placed under the skin and the incision closed. Following a recovery period (5-10 days), the animals underwent MRI. We performed baseline assessment of left ventricle function, and repeated LV measurement during a 15-min coronary occlusion and again during a 60-min reperfusion period following reopening of the coronary artery. The occluder was successfully placed in 40 of 44 animals. Four developed intraoperative complications; two large myocardial infarction, two terminal bleeding. Six died in the week following surgery, [four sudden deaths (presumed arrhythmic), one anterior infarction, one sepsis]. Cine-MRI demonstrated localised hypokinesia in 31 of the remaining 34 animals. LV ejection fraction (EF) was reduced from 63 +/- A 7 % at baseline, to 49 +/- A 9 % during coronary occlusion. LV EF recovered to 61 +/- A 2 %. The area at risk on staining of the heart was 41.9 +/- A 15.8 %. This method allows the effects of ischemia/reperfusion to be studied before, during, and after coronary occlusion. Ischemia can be caused while the animal is in the MRI. This new and clinically relevant small animal model is a valuable tool to study the effects of single or repeated coronary occlusion/reperfusion in real-time.