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Effects of OP2113 on Myocardial Infarct Size and No Reflow in a Rat Myocardial Ischemia/Reperfusion Model

Authors :
David Brown
Lifu Zhao
Justin B. Perry
Rodrigue Rossignol
Nivea Dias Amoedo
Wangde Dai
Bruno Le Grand
Juan Carreno
Robert A. Kloner
Aurelie Boucard
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM)
Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM)
Source :
Cardiovascular Drugs and Therapy, Cardiovascular Drugs and Therapy, Springer Verlag, 2021, ⟨10.1007/s10557-020-07113-7⟩
Publication Year :
2021
Publisher :
Springer Science and Business Media LLC, 2021.

Abstract

Purpose : The present study was to determine whether OP2113 could limit myocardial infarction size and the no-reflow phenomenon in a rat myocardial ischemia/reperfusion model. Methods : Rat heart–isolated mitochondria (RHM) were used to investigate mitochondrial respiration and mitochondrial reactive oxygen species (mtROS) generation both in normal conditions and in ischemia/reperfusion-mimicking conditions (using high concentrations of succinate). Human skeletal muscle myoblasts (HSMM) in culture were used to investigate the cellular intermittent deprivation in energy substrates and oxygen as reported in ischemia/reperfusion conditions. In vivo, rats were anesthetized and subjected to 30 min of left coronary artery occlusion followed by 3 h of reperfusion. Rats were randomized to receive OP2113 as an intravenous infusion starting either 5 min prior to coronary artery occlusion (preventive), or 5 min prior to reperfusion (curative), or to receive vehicle starting 5 min prior to coronary artery occlusion. Infusions continued until the end of the study (3 h of reperfusion). Results : RHM treated with OP2113 showed a concentration-dependent reduction of succinate-induced mtROS generation. In HSMM cells, OP2113 treatment (5–10 μM) during 48H prevented the reduction in the steady-state level of ATP measured just after reperfusion injuries and decreased the mitochondrial affinity to oxygen. In vivo, myocardial infarct size, expressed as the percentage of the ischemic risk zone, was significantly lower in the OP2113-treated preventive group (44.5 ± 2.9%) versus that in the vehicle group (57.0 ± 3.6%; p

Details

ISSN :
15737241 and 09203206
Volume :
36
Database :
OpenAIRE
Journal :
Cardiovascular Drugs and Therapy
Accession number :
edsair.doi.dedup.....533e7bb530b792ac55b79c02051f3369