Kim Weon, Jeong Myung Ho, Sim Doo Sun, Hong Young Joon, Song Ho Cheon, Park Jong Tae, Ahn Young Keun
Cardiovascular Division, Department of Internal Medicine, Kyung Hee University, Seoul, Korea.
Heart Vessels. 2011 May;26(3):342-8. doi: 10.1007/s00380-010-0022-3. Epub 2010 Oct 21.
We have developed a porcine model of acute myocardial infarction (AMI) and ischemic heart failure by transcatheter intracoronary injection of ethyl alcohol and observed pathologic changes induced in the alcohol-injured coronary artery and infarcted myocardium. In a total of 12 female pigs, anteroseptal AMI was induced by transcatheter delivery of 1 mL of 99.9% ethyl alcohol using a 2.5 mm diameter over-the-wire balloon catheter in the left anterior descending artery (LAD). Another five pigs underwent the sham operation, and the differences in left ventricular (LV) dimension and LV ejection fraction between these pigs and those injected with ethyl alcohol were evaluated. Follow-up coronary and LV angiography, echocardiography and histopathology were performed at 4 weeks after the procedure. Myocardial SPECT using (201)Tl (and (99m)Tc-MIBI) and triphenyl tetrazolium chloride (TTC) stain were performed and compared. Procedure-related death occurred in two pigs with proximal LAD occlusion. Four pigs suffered from ventricular tachycardia, which converted to sinus rhythm by DC cardioversion. Follow-up coronary angiography at 4 weeks revealed persistent total occlusion in all pigs. Echocardiogram showed decreased apicoanteroseptal wall motion with an ejection fraction of 46.5 ± 3.3% and nonsignificantly changed LV dimensions. Myocardial SPECT revealed a perfusion defect in the apicoanterior wall in all subjects (percent area of the perfusion defect = 22.1 ± 2.50%). The percentage of myocardium not stained by TTC was 23.1 ± 2.25%. Histologic examination revealed severe fibrosis in the infarcted myocardium and massive thrombus with organization and calcification in the alcohol-injured coronary artery. The porcine model of AMI obtained by intracoronary alcohol injection provides a safe and reproducible method for the research and development of new therapeutic modalities for MI and end-stage heart failure.
我们通过经导管冠状动脉内注射乙醇建立了急性心肌梗死(AMI)和缺血性心力衰竭的猪模型,并观察了乙醇损伤的冠状动脉和梗死心肌中诱导的病理变化。在总共12只雌性猪中,使用直径2.5mm的金属丝外球囊导管在左前降支(LAD)经导管输送1mL 99.9%乙醇诱导前间隔AMI。另外5只猪接受假手术,并评估这些猪与注射乙醇的猪之间左心室(LV)尺寸和LV射血分数的差异。在手术后4周进行随访冠状动脉和LV血管造影、超声心动图和组织病理学检查。使用(201)Tl(和(99m)Tc-MIBI)进行心肌SPECT检查,并与氯化三苯基四氮唑(TTC)染色进行比较。2只近端LAD闭塞的猪发生了与手术相关的死亡。4只猪出现室性心动过速,通过直流电复律转为窦性心律。4周时的随访冠状动脉造影显示所有猪均持续完全闭塞。超声心动图显示心尖前间隔壁运动减弱,射血分数为46.5±3.3%,LV尺寸无显著变化。心肌SPECT显示所有受试者的心尖前壁均有灌注缺损(灌注缺损面积百分比=22.1±2.50%)。未被TTC染色的心肌百分比为23.1±2.25%。组织学检查显示梗死心肌中有严重纤维化,乙醇损伤的冠状动脉中有大量血栓形成、机化和钙化。通过冠状动脉内注射乙醇获得的猪AMI模型为MI和终末期心力衰竭新治疗方法的研发提供了一种安全且可重复的方法。