The Effect of EPLerenone on Ischemia Reperfusion Injury in Human myoCARDium

Ischemia-reperfusion Injury Clinical Trial

— EPLICARD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02118753
• Other study ID #: EPLICARD
• Status: Completed
• Phase: N/A
• First received: March 14, 2014
• Last updated: January 11, 2016
• Start date: March 2014
• Est. completion date: January 2016

Study information

• Verified date: January 2016
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ischemia
• Ischemia-reperfusion Injury
• Reperfusion Injury

Intervention

Drug:
• Eplerenone
eplerenone administered ex vivo (to the organ bath in which human atrial tissue is exposed)

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. Epub 2006 Jul 24. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	contractile function after simulated ischemia and reperfusion in response to eplerenone	The recovery of contractile function (% of baseline) in human myocardial tissue after simulated ischemia and reperfusion in 2 trabeculae will be compared: 1 of the trabeculae will be exposed to eplerenone, the other to vehicle.; We will use the experimental set up as described by Speechly-Dick et al. with small modifications to allow simultaneous measurement of 2 trabeculae from 1 patient. The two trabeculae will be dissected and vertically suspended in an organ bath and linked to a force transducer. During electrical field stimulation, we will calculate the developed force (difference between maximal tension during contraction and minimal tension during relaxation), maximal speed of tension development during contraction and maximal speed of tension during relaxation. We will average these parameters for baseline, and during the experiment. Functional recovery will be expressed as a percentage of baseline.	210 minutes	No