The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium

The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)

In the laboratory, the researchers will investigate whether the drug eplerenone improves contractile function after ischemia and reperfusion in heart tissue.

In animal studies, the mineralocorticoid receptor antagonist eplerenone appears to limit myocardial infarct size. This cardioprotective effect might explain, at least in part, the beneficial effect on mortality of eplerenone in patients with heart failure. Previous animal studies suggest that this cardioprotective effect is mediated by an increased formation of the endogenous nucleoside adenosine.

Our objective is to study for the first time in human myocardial tissue ex vivo wether eplerenone limits ischemia reperfusion injury and whether this is mediated by adenosine receptor stimulation.

From patients undergoing open heart surgery, the right atrial appendage will be harvested by the cardiothoracic surgeon. In the laboratory, two trabeculae will be dissected and suspended in an organ bath. Contraction will be induced by electrical field stimulation. Recovery of contractile force after a period of simulated ischemia and reperfusion will be used as an endpoint of ischemia-reperfusion injury.

The trabeculae of each patient will be randomized to pretreatment with A)ischemic preconditioning (IP) of no IP as a positive control experiment; B)eplerenone or vehicle; C)eplerenone with or without caffeine; and D)aldosterone with and without eplerenone.

Inclusion Criteria:

• age>18 years
• willing to sign informed consent
• planned elective surgery with extracorporal circulation

Exclusion Criteria:

• use of theophylline
• use of sulfonylureas
• use of oral antiarrhythmics (not beta blockers)
• use of dipyridamole, use of mineralocorticoid receptor antagonists
• atrial arrhythmias
• right ventricular failure
• known atrial enlargement