Choy Jenny S, Hubbard Terry, Wang Haifeng, Awakeem Yousif, Khosravi Pouya, Khadivi Bahram, Navia Jose A, Stone Gregg W, Lee Lik Chuan, Kassab Ghassan S
California Medical Innovations Institute, Inc., San Diego, CA, United States.
3DT Holdings, LLC, San Diego, CA, United States.
Front Bioeng Biotechnol. 2024 May 10;12:1386713. doi: 10.3389/fbioe.2024.1386713. eCollection 2024.
Prompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10 min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis.
AMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10 min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect.
SARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2 min during retroperfusion, suggest a "washout" effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers.
RI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.
急性心肌梗死（AMI）后冠状动脉的及时再灌注对于将心脏损伤降至最低至关重要。然而，心肌可能会因血流恢复本身（再灌注损伤，RI）而遭受额外损伤。本研究的目的是基于冲洗假说，证明选择性自逆行灌注（SARP）进行短时间预处理（10分钟）可减轻再灌注损伤。
通过闭塞左前降支（LAD）动脉，在23头猪（3组）中诱导急性心肌梗死。在SARP-b组（SARP球囊充气）和SARP-nb组（SARP球囊未充气）中，在解除动脉闭塞前，通过大冠状静脉进行10分钟的动脉血逆行灌注。使用冠状动脉循环的数学模型来模拟SARP过程并评估潜在的冲洗效果。
SARP在LAD闭塞期间恢复了左心室功能。与SARP-nb组和对照组相比，SARP-b组的射血分数恢复到基线水平。对照组的梗死面积明显大于SARP-b组和SARP-nb组。与SARP-nb组和对照组相比，SARP-b组的收缩末期壁厚得以保留。在逆行灌注期间每2分钟测量一次的分析物值（pH、乳酸、葡萄糖等）表明，“冲洗”效应是SARP减少梗死面积的一个重要作用机制。通过SARP，这些值逐渐接近基线水平。数学模型也证实了示踪剂可能存在冲洗效应。
通过短暂延迟动脉血流恢复，同时用SARP预处理梗死以通过冲洗机制恢复体内稳态，可以减轻再灌注损伤。
