Attenuation of ischemia–reperfusion injury by intracoronary chelating agent administration

Donghoon Han,In-Ho Chae,Chang-Hwan Yoon,Si-Hyuck Kang,Tae-Jin Youn

doi:10.1038/s41598-022-05479-2

Abstract

Ischemia–reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and thus abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. We investigated the efficacy of intracoronary ethylenediaminetetraacetic acid (EDTA) administration as an adjunctive treatment to coronary intervention to reduce IR injury in a swine model. We occluded the left anterior descending artery for 1 h. From the time of reperfusion, we infused 50 mL of EDTA-based chelating agent via the coronary artery in the EDTA group and normal saline in the control group. IR injury was identified by myocardial edema on echocardiography. Tetrazolium chloride assay revealed that the infarct size was significantly lower in the EDTA group than in the control group, and the salvage percentage was higher. Electron microscopy demonstrated that the mitochondrial loss in the cardiomyocytes of the infarcted area was significantly lower in the EDTA group than in the control group. Echocardiography after 4 weeks showed that the remodeling of the left ventricle was significantly less in the EDTA group than in the control group: end-diastolic dimension 38.8 ± 3.3 mm vs. 43.9 ± 3.7 mm (n = 10, p = 0.0089). Left ventricular ejection fraction was higher in the EDTA group (45.3 ± 10.3 vs. 34.4 ± 11.8, n = 10, respectively, p = 0.031). In a swine model, intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction.

Highlights

Ischemia–reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction
We investigated whether intracoronary administration of ethylenediaminetetraacetic acid (EDTA) after reperfusion could reduce calcium in the injured tissue, prevent the transition of mitochondrial permeability transition pore (mPTP) and mitochondrial dysfunction, and thereby reduce IR injury in a swine IR injury model
infarcted segment (IFS) was significantly lower and, the salvage percentage was significantly higher in the EDTA group than in the control group (Fig. 1D,E)

Summary

Introduction

Ischemia–reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. Intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction. Three mechanisms inducing reperfusion injury are reactive oxygen species, Ca2+ overload, and pH correction after reperfusion, all of which contribute to the opening of the mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and myocardial necrosis This is an acute process occurring within several minutes to 30 min after r eperfusion[4]. Clinical cardioprotective research has been challenging, novel therapies are still needed

Methods

Results

Conclusion