Dib Nabil, Diethrich Edward B, Campbell Ann, Gahremanpour Amir, McGarry Michael, Opie Shaun R
Arizona Heart Institute, 2632 N 20th St, Phoenix, AZ, 85006, USA; Arizona State University, Tempe, AZ, USA.
J Pharmacol Toxicol Methods. 2006 May-Jun;53(3):256-63. doi: 10.1016/j.vascn.2005.10.005. Epub 2006 Feb 7.
The aim of this study was to develop a percutaneous, low risk, and reproducible technique of MI that simulates human disease.
MI was induced in 44 swine (32.8+/-7.2 kg) by percutaneous embolization coil deployment in the left anterior descending coronary artery. Hemodynamic measurements, left heart catheterization, and echocardiography were performed pre, post, and 30 days after MI. 3D NOGA viability mapping was performed at baseline and 30 days. Excised hearts were examined histologically.
Pre-MI mortality was 6.8% and 24 h mortality was 13.6%. All pigs that survived 24 h after MI remained alive at 30 days. The mean left ventricular ejection fraction decreased from 58.4% to 42.1% (p<0.001) at 30 days. The average thrombolysis in myocardial infarction score was 3, 0, and 1.5 at baseline, post-MI, and 30 days, respectively. At 30 days, the end diastolic diameter, end diastolic volume, end systolic volume, and wall motion index increased from 3.76 to 3.89 cm, 32.5 to 50.0 ml, 14.9 to 27.0 ml, and 1.01 to 1.38, respectively (all p<0.05), while the ejection fraction decreased from 56.5% to 49.4% (p<0.01). Additionally, at 30 days, statistically significant reductions in both unipolar and bipolar voltage in the mid and apical regions of the left ventricle were observed. Postmortem pathology showed a transmural scar in the apical anteroseptal regions with fibrosis in the MI region, which accounted for 14.8% and 14.2% of the total left and right ventricular myocardial area and volume, respectively.
This model of MI is reliable, reproducible, has a pathophysiology similar to humans, and a lower mortality and ventricular fibrillation rates compared to other models. This model may be used to evaluate the effects of pharmacologics, gene therapy, and stem cell transplantation for the treatment of cardiovascular disease as well as studying mechanisms of cardiac remodeling.
本研究的目的是开发一种经皮、低风险且可重复的心肌梗死技术，该技术可模拟人类疾病。
通过在左前降支冠状动脉中经皮部署栓塞线圈，在44头猪（32.8±7.2千克）中诱导心肌梗死。在心肌梗死前、后及30天后进行血流动力学测量、左心导管检查和超声心动图检查。在基线和30天时进行三维NOGA存活心肌图绘制。对切除的心脏进行组织学检查。
心肌梗死前死亡率为6.8%，24小时死亡率为13.6%。所有心肌梗死后存活24小时的猪在30天时仍存活。30天时，平均左心室射血分数从58.4%降至42.1%（p<0.001）。心肌梗死溶栓评分在基线、心肌梗死后和30天时分别为3、0和1.5。30天时，舒张末期直径、舒张末期容积、收缩末期容积和壁运动指数分别从3.76厘米增加至3.89厘米、32.5毫升增加至50.0毫升、14.9毫升增加至27.0毫升以及从1.01增加至1.38（均p<0.05），而射血分数从56.5%降至49.4%（p<0.01）。此外，在30天时，观察到左心室中部和心尖区域的单极和双极电压均有统计学意义的降低。尸检病理学显示心尖前间隔区域有透壁瘢痕，心肌梗死区域有纤维化，分别占左、右心室心肌总面积和总体积的14.8%和14.2%。
这种心肌梗死模型可靠、可重复，具有与人类相似的病理生理学，与其他模型相比死亡率和心室颤动率更低。该模型可用于评估药物、基因治疗和干细胞移植对心血管疾病治疗的效果以及研究心脏重塑机制。
