Eplerenone does not limit ischemia-reperfusion injury in human myocardial tissue.

Article history: Received 24 March 2016 Accepted 16 April 2016 Available online 22 April 2016 Background: Despite rapid reperfusion, mortality and morbidity in patients with an acute myocardial infarction remain significant. Therefore, novel pharmacological strategies to further limit ischemia–reperfusion (IR) injury are warranted. In animal models of myocardial infarction, mineralocorticoid receptor antagonists potently limit infarct size. In the current studywe aimed to translate these findings to the human situation and investigated for the first time in human myocardial tissue whether eplerenone limits IR-injury. Methods: In 24 patients undergoing elective cardiac surgery, the right atrial appendage was harvested, and two trabeculae were dissected from each appendage and suspended in an organ bath. We induced contraction by electrical field stimulation. Recovery of contractile force after a period of simulated ischemia and reperfusion was used as well-validated endpoint of IR-injury. From each patients, the trabeculae were randomized to either ischemic preconditioning (IP) or no IP (n= 12; positive control experiment) or to superfusion with eplerenone (10 μM) or vehicle (n = 12) in a paired approach. Results: IP improved recovery from19.9 (SEM3.3)% to 26.3 (SEM 4.3)% (p b 0.05). During vehicle and eplerenone superfusion,mean recovery of contractile function after simulated ischemia and reperfusionwas 45.2 (SEM5.6)% and 36.5 (SEM 4.1)% (p = 0.14). Conclusion: Eplerenone does not limit IR-injury in human atrial tissue ex vivo. Our results are in sharp contrast to preclinical studies demonstrating cardioprotective effects of mineralocorticoid receptor antagonist. With great interest we await the results of the MINIMISE-STEMI study, in which the effect of MR antagonism onmyocardial infarct size in humans is currently under investigation. © 2016 The Author(s). Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).