The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium (EPLICARD)

Radboud University Medical Center

Status: Completed

Conditions: Ischemia-reperfusion Injury

Treatments: Drug: Eplerenone

Study type: Interventional

Funder types: Other

Identifiers

NCT02118753

EPLICARD

Details and patient eligibility

About

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

Full description

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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

ischemic preconditioning

No Intervention group

Description:

After baseline recordings of contractile function, the investigators will assign 2 trabeculae of each patient to either a stimulus for (1) ischemic preconditioning (IP) or (2) no IP. Subsequently, the trabeculae will be exposed to 90 min of ischemia, followed by 120 minutes of recovery. The investigators will measure the recovery of contractile function in both trabeculae. This experiment serves as a positive control, to ensure that our model is still working properly.

eplerenone

Experimental group

Description:

In the next patients, a similar ischemia-reperfusion experiment will be performed, but now the 2 trabeculae will be randomized to pretreatment with eplerenone or DMSO. The percentage recovery (compared to baseline) of contractile force of the trabeculae at the end of reperfusion will serve as the primary endpoint.

Treatment:

Drug: Eplerenone