Thankam Finosh G, Radwan Mohamed, Keklikian Angelo, Atwal Manreet, Rai Taj, Agrawal Devendra K
Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA.
Cardiol Cardiovasc Med. 2022;6(5):466-472. doi: 10.26502/fccm.92920284. Epub 2022 Aug 24.
Despite the recent advancements in the cardiac regenerative technologies, the lack of an ideal translationally relevant experimental model simulating the clinical setting of acute myocardial infarction (MI) hurdles the success of cardiac regenerative strategies.
We developed a modified minimally invasive acute MI model in Yucatan miniswine by catheter-driven controlled occlusion of LCX branches for regenerative cardiology. Using a balloon catheter in three pigs, the angiography guided occlusion of LCX for 10-15 minutes resulted in MI induction which was confirmed by the pathological ECG changes compared to the baseline control.
Ejection fraction was considerably decreased post-procedure compared to the baseline. Importantly, the highly sensitive MI biomarker Troponin I was significantly increased in post-MI and follow-up groups along with LDH and CCK than the baseline control. The postmortem infarct zone tissue displayed the classical features of MI including ECM disorganization, hypertrophy, inflammation, and angiogenesis confirming the MI at the tissue level.
The present model possesses the advantage of minimal mortality, simulating the pathological features of clinical MI and the suitability for injectable regenerative therapies suggesting the translational significance in regenerative cardiology.
尽管心脏再生技术最近取得了进展，但缺乏一个理想的、与临床相关的实验模型来模拟急性心肌梗死（MI）的临床情况，这阻碍了心脏再生策略的成功。
我们通过导管驱动控制闭塞尤卡坦小型猪的左旋支（LCX）分支，为再生心脏病学开发了一种改良的微创急性心肌梗死模型。在三只猪中使用球囊导管，在血管造影引导下闭塞LCX 10 - 15分钟导致心肌梗死，与基线对照相比，通过病理性心电图变化得到证实。
与基线相比，术后射血分数显著降低。重要的是，与基线对照相比，心肌梗死后和随访组中高敏感性心肌生物标志物肌钙蛋白I以及乳酸脱氢酶（LDH）和胆囊收缩素（CCK）显著升高。尸检梗死区组织显示出心肌梗死的典型特征，包括细胞外基质紊乱、肥大、炎症和血管生成，在组织水平上证实了心肌梗死。
本模型具有死亡率低的优点，模拟了临床心肌梗死的病理特征，适用于可注射的再生治疗，表明在再生心脏病学中具有转化意义。
