The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs
The bottleneck stent model for chronic myocardial ischemia and heart failure in pigs
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DOI：
10.1152/ajpheart.00561.2013
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发表时间：
2013-11-01
影响因子：
4.8
通讯作者：
Yla-Herttuala, Seppo
中科院分区：
文献类型：
--
作者：
Rissanen, Tuomas T.;Nurro, Jussi;Yla-Herttuala, Seppo
慢性心肌缺血和心力衰竭的大型动物模型对于开发新的治疗方法至关重要。在这项研究中，我们开发了一种新的经皮单血管和双血管模型的慢性心肌缺血使用的支架涂层聚四氟乙烯管形成的瓶颈形状。1 wk后将瓶颈支架植入左前降支（LAD）近端或回旋支（LCX）近端，或同时植入LCX近端和LAD中段（双支模型），并随访4-5 wk。评估射血分数（EF）、梗死面积、侧支生长和心肌灌注。猪被给予抗惊厥药物以防止猝死。抗血小板药物的持续时间可以调节瓶颈支架的闭塞时间和心肌梗死的时间。血流储备分数测量和正电子发射断层扫描成像显示，在近端LAD模型中，瓶颈支架植入术覆盖了超过50%的左心室后出现严重缺血。完全冠状动脉闭塞是必要的显着侧支血管生长，这主要是发生在第一周后支架闭塞。动态和竞争的侧枝生长模式进行了观察。支架植入后4周，左回旋支模型和前降支模型的EF分别从64%下降至41%和44%，左回旋支和前降支模型的梗死左心室分别为12%和21%。在LCX和LAD模型中死亡率分别为32%和37%，但在双血管疾病模型中死亡率非常高（71%）。在近端LAD或LCX中植入新型瓶颈支架是可逆性心肌缺血（开放支架）和缺血性心力衰竭（闭塞支架）的新型猪模型，对于开发新的治疗方法是可行的。
A large animal model of chronic myocardial ischemia and heart failure is crucial for the development of novel therapeutic approaches. In this study we developed a novel percutaneous one-and two-vessel model for chronic myocardial ischemia using a stent coated with a polytetrafluoroethylene tube formed in a bottleneck shape. The bottleneck stent was implanted in the proximal left anterior descending (LAD) or proximal circumflex artery (LCX), or in both proximal LCX and mid LAD 1 wk later (2-vessel model), and pigs were followed for 4-5 wk. Ejection fraction (EF), infarct size, collateral growth, and myocardial perfusion were assessed. Pigs were given antiarrhythmic medication to prevent sudden death. The occlusion time of the bottleneck stent and the timing of myocardial infarction could be modulated by the duration of antiplatelet medication. Fractional flow reserve measurements and positron emission tomography imaging showed severe ischemia after bottleneck stenting covering over 50% of the left ventricle in the proximal LAD model. Complete coronary occlusion was necessary for significant collateral growth, which mostly had occurred already during the first wk after the stent occlusion. Dynamic and competitive collateral growth patterns were observed. EF declined from 64 to 41% in the LCX model and to 44% in the LAD model 4 wk after stenting with 12 and 21% infarcted left ventricle in the LCX and LAD models, respectively. The mortality was 32 and 37% in the LCX and LAD models but very (71%) high in the two-vessel disease model. The implantation of a novel bottleneck stent in the proximal LAD or LCX is a novel porcine model of reversible myocardial ischemia (open stent) and ischemic heart failure (occluded stent) and is feasible for the development of new therapeutic approaches.