Mineralocorticoid Receptor Inhibition in Myocardial Infarction

All animal experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (Publication No. 85–23, revised 1985). All procedures were approved by the Regierung von Unterfranken (Würzburg, Germany; permit No. 54–2531.01-15/07) and by the Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit (Oldenburg, Germany; permit No. 33.12-42502-04-11/0644 and 33.9-42502-04-13/1124). Adult Nr3c2^tm2Gsc (MR^flox, WT controls), Nr3c2^tm2GscLyz2tm1(cre)lfo/J (MR^LysMCre), and C57Bl/6 mice of both sexes were used in this study. Liposome-encapsulated RU28318 (2 µmol/kg) or liposome-encapsulated eplerenone (20 µmol/kg) were administered intraperitoneally (100 μmol lipid per kg) in C57BL/6 mice at the onset of myocardial infarction. Control C57BL/6 mice were injected with equal volumes of plain (MR antagonists lacking) liposome. In additional experimental groups, starting immediately after coronary ligation, C57BL/6 mice were randomly selected for eplerenone (100 mg/kg of body weight) or placebo treatment (5% arabic gum) administered by gavage once daily. Mice subjected to coronary artery ligation were sacrificed at days 1, 3, or 7 after surgery. Mice were excluded from the analyses for 2 reasons: perioperative death (within the first 12 hours after surgery) and MI size <40.