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Effects of OP2113 on Myocardial Infarct Size and No Reflow in a Rat Myocardial Ischemia/Reperfusion Model
- 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
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Ischemia
Hemodynamics
Infarction
Ischemia/reperfusion injury
Cardio-protection
030204 cardiovascular system & hematology
Infarct size
03 medical and health sciences
0302 clinical medicine
In vivo
Internal medicine
medicine
Myocyte
Pharmacology (medical)
Myocardial infarction
Pharmacology
Coronary artery occlusion
business.industry
No-reflow phenomenon
Skeletal muscle
General Medicine
medicine.disease
Mitochondrial ROS generation
ST elevation myocardial infarction
030104 developmental biology
medicine.anatomical_structure
No reflow phenomenon
Cardiology
Cardiology and Cardiovascular Medicine
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- ISSN :
- 15737241 and 09203206
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Drugs and Therapy
- Accession number :
- edsair.doi.dedup.....533e7bb530b792ac55b79c02051f3369