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Cardioprotection of the enkephalin analog Eribis peptide 94 in a rat model of ischemia and reperfusion is highly dependent on dosing regimen and timing of administration

Journal article
Authors Elias Spanos
Lars O Karlsson
Björn Redfors
Yangzhen Shao
Elmir Omerovic
Irina Bobrova
Lars Grip
Niklas Bergh
Published in European Journal of Pharmacology
Volume 747
Pages 1-6
ISSN 0014-2999
Publication year 2015
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 1-6
Language en
Links dx.doi.org/10.1016/j.ejphar.2014.11...
Subject categories Cardiovascular medicine

Abstract

Eribis Peptide 94 (EP94) is an enkephalin analog with cardioprotective properties in ischemia and reperfusion. The aim of the present study was to define the optimal timing and dosing of the administration of EP94 during ischemia and reperfusion in a rat model. 172 anesthetized and mechanically ventilated male Sprague-Dawley rats were randomly assigned to different administration protocols of EP94 and subjected to 30 or 40min of coronary artery occlusion followed by 2h of reperfusion. EP94 was administered intravenously at different doses and time intervals. Area at risk (AAR) and infarct size (IS) were determined by staining with Evans Blue (EB) and Triphenyl tetrazolium chloride (TTC), respectively. EP94 reduced IS/AAR when administered as a double bolus (0.5µg/kg per dose), whereas single (1μg/kg) or triple boluses (0.5μg/kg per dose) did not confer any protection. Reduction of IS/AAR was of highest magnitude if EP94 was administered 5 and 0min before the 30min ischemic period (47% reduction, P<0.05), with declining cardioprotective effect with later administration during ischemia. When EP94 was administered after 15 and 20min of a 40-min ischemic period, reduction of IS/AAR was of the same magnitude as when given after 5 and 10min of a 30-min ischemic period. It is concluded that EP94 confers cardioprotection after double bolus administration. The effects are highly dependent on the timing of administration in relation to ischemia and reperfusion. Time of reperfusion from drug administration seems to be more critical than the total duration of ischemia.

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