Clinical trial NCT02118753: The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium
Official title: The Effect of Eplerenone on Ischemia Reperfusion Injury in Human Myocardium (EPLICARD Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemia-reperfusion Injury
Keywords: ischemia-reperfusion injury
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2014-04-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: contractile function after simulated ischemia and reperfusion in response to eplerenone
timeFrame: 210 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Niels P. Riksen, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: Henri A. van Swieten, Prof dr ir
role: PRINCIPAL_INVESTIGATOR
References:
citation: Riksen NP, Zhou Z, Oyen WJ, Jaspers R, Ramakers BP, Brouwer RM, Boerman OC, Steinmetz N, Smits P, Rongen GA. Caffeine prevents protection in two human models of ischemic preconditioning. J Am Coll Cardiol. 2006 Aug 15;48(4):700-7. doi: 10.1016/j.jacc.2006.04.083. Epub 2006 Jul 24.
citation: Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res. 1995 Nov;77(5):1030-5. doi: 10.1161/01.res.77.5.1030.