Ischemia, reperfusion and preconditioning: traditional and new approaches for treatment of myocardial infarction

2016 ◽  
Vol 14 (3) ◽  
pp. 3-11
Author(s):  
Abdrei V. Lyubimov ◽  
Petr D. Shabanov
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trials ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Katp Channels ◽  
Instrumental Control ◽  
Pharmacological Preconditioning

The review is devoted to the questions of improvement of the efficacy of myocardial infarction treatment by means of pharmacological drugs possessing pre- or postconditioning effect. The proofs of clinical efficacy of reperfusional therapy of the myocardial infarction are observed using examples of adenosine, activators of KATP channels (diazoxide and nicorandil), opiates (fentanyl, morphine) and some other drugs. The data are analyzed from the point of modern view of molecular mechanisms of hypoxia, the findings of objective laboratory and instrumental control in therapy of myocardial infarction in differend known clinical trials. It is concluded that pharmacological preconditioning is perspective approach in therapy of the acute myocardial infarction both in animal models and in humans.

scholarly journals The role of aldosterone inhibitors in cardiac ischemia–reperfusion injury

2020 ◽  
pp. 1-12
Author(s):  
Nevena Dragasevic ◽  
Vladimir Jakovljevic ◽  
Vladimir Zivkovic ◽  
Nevena Draginic ◽  
Marijana Andjic ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trials ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Infarct Zone ◽  
Vast Number ◽  
Postinfarction Remodeling

Myocardial ischaemia–reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.

Cardiomyocyte-Specific JunD Overexpression Increases Infarct Size following Ischemia/Reperfusion Cardiac Injury by Downregulating Sirt3

2019 ◽  
Vol 120 (01) ◽  
pp. 168-180 ◽  
Author(s):  
Alexander Akhmedov ◽  
Fabrizio Montecucco ◽  
Sarah Costantino ◽  
Daria Vdovenko ◽  
Ariane Schaub Clerigué ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Cellular Proliferation ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Data Set

AbstractIschemia/reperfusion (I/R) injury in acute myocardial infarction activates several deleterious molecular mechanisms. The transcription factor JunD regulates pathways involved in oxidative stress as well as in cellular proliferation, differentiation, and death. The present study investigated the potential role of JunD as a modulator of myocardial injury pathways in a mouse model of cardiac I/R injury. Infarct size, systemic and local inflammation, and production of reactive oxygen species, as well as cytosolic and mitochondrial apoptotic pathways were investigated in adult males after myocardial I/R. In wild-type (WT) mice, 30 minutes after ischemia and up to 24 hours following reperfusion, cardiac JunD messenger ribonucleic acid expression was reduced while JunB increased. Cardiac-specific JunD overexpressing mice (JunDTg/0 ) displayed larger infarcts compared with WT. However, postischemic inflammatory or oxidative responses did not differ. JunD overexpression reduced Sirt3 transcription by binding to its promoter, thus leading to mitochondrial dysfunction, myocardial cell death, and increased infarct size. On the other hand, JunD silencing reduced, while Sirt3 silencing increased infarct size. In human myocardial autopsy specimens, JunD-positive areas within the infarcted left ventricle staining corresponded to undetectable Sirt3 areas in consecutive sections of the same heart. Cardiac-specific JunD overexpression increases myocardial infarct size following I/R. These effects are mediated via Sirt3 transcriptional repression, mitochondrial swelling, and increased apoptosis, suggesting that JunD is a key regulator of myocardial I/R injury. The present data set the stage for further investigation of the potential role of Sirt3 activation as a novel target for the treatment of acute myocardial infarction.

scholarly journals Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Yin ◽  
Yang Zheng ◽  
Xujie Zhai ◽  
Xin Zhao ◽  
Lu Cai
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Protective Effect ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Patients ◽  
Protective Mechanisms ◽  
Gsk 3Β ◽  
Pathogenic Effects

Ischemic preconditioning (IPC) or postconditioning (Ipost) is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

Inhibition of mitochondrial fission as a novel therapeutic strategy to reduce mortality upon myocardial infarction

2018 ◽  
Vol 132 (20) ◽  
pp. 2163-2167 ◽  
Author(s):  
Hannah A. Cooper ◽  
Satoru Eguchi
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Mitochondrial Fission ◽  
Future Research ◽  
Mitochondrial Homeostasis ◽  
Acute Mi ◽  
Future Research Directions ◽  
Receive Treatment

Ischemia reperfusion (I/R) injury is a common event following myocardial infarction (MI) resulting in excessive oxidative stress, calcium overload, inflammation, and cardiomyocyte death. Mitochondrial homeostasis including their dynamics are imbalanced in cardiac I/R injury in favor of increased mitochondrial fission. Inhibition of mitochondrial fission prior to I/R injury is protective and improves cardiac function following MI. Clinically, patients with MI often receive treatment following initiation of the ischemic event. Thus, treatments with more realistic timing would have better translational value and are important to research. In a recent study published in Clinical Science, Maneechote et al. [Clin. Sci. (2018) 132, 1669–1683] examined the effect of inhibiting mitochondrial fission using the mitochondrial division inhibitor (Mdivi-1) at different time points, pre-ischemia, during-ischemia, and upon onset of reperfusion, in a rat cardiac I/R model. The findings showed the greatest cardiac function improvement with pre-ischemia treatment along with decreased mitochondrial fragmentation and increased mitochondrial function. Mdivi-1 given during ischemia and at onset of reperfusion also improved cardiac function, but to a lesser extent than pre-ischemia intervention. Maneechote et al. postulated that the LV protection by Mdivi-1 in cardiac I/R could be due to an improvement in mitochondrial dysfunction through attenuating excessive mitochondrial fission which then reduces apoptotic myocytes. Their findings provide new insights into future treatment of patients suffering acute MI which could consider targetting the excessive mitochondrial fission during cardiac ischemia or at onset of reperfusion. Here, we will further discuss the background of the study, potential molecular mechanisms of mitochondrial fission, consequences of the fission, and future research directions.

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