Attenuation of ischemia–reperfusion injury by intracoronary chelating agent administration

• Published in: Scientific reports Vol. 12; no. 1; p. 2050
• Main Authors: Han, Donghoon, Kang, Si-Hyuck, Yoon, Chang-Hwan, Youn, Tae-Jin, Chae, In-Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/80/304; 692/4019/2776; Acetic acid; Animals; Aorta, Thoracic - pathology; Cardiomyocytes; Chelating agents; Chelating Agents - administration & dosage; Chelating Agents - therapeutic use; Coronary artery; Disease Models, Animal; Echocardiography; Edema; Edetic acid; Edetic Acid - therapeutic use; Electron microscopy; Heart; Heart attacks; Humanities and Social Sciences; Ischemia; Male; Mitochondria; Mitochondria - metabolism; multidisciplinary; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Myocardial Ischemia - pathology; Myocardial Ischemia - therapy; Myocardial Reperfusion Injury - drug therapy; Patients; Reperfusion; Salvage Therapy - methods; Science; Science (multidisciplinary); Stroke Volume - drug effects; Swine; Triphenyltetrazolium chloride; Ventricle; Ventricular Function, Left - drug effects; Ventricular Remodeling - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-05479-2

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.