Possibilities of pharmacological correction of reperfusion injury of ischemic myocardium (review)

2021 ◽  
Vol 19 (3) ◽  
pp. 259-267
Author(s):  
Konstantin G. Gurevich ◽  
Aleksandr L. Urakov ◽  
Eugeniy L. Fisher ◽  
Timer A. Abzalilov ◽  
Kseniya A. Khairzamanova ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Heart Muscle ◽  
Ischemic Myocardium ◽  
Cardiac Ischemia ◽  
Experimental Conditions ◽  
Irreversible Damage ◽  
Pharmacological Agents ◽  
Late Reperfusion

Timely and effective reperfusion in ischemia and reoxygenation in hypoxia of the heart muscle prevent myocardial infarction. Delayed reperfusion and reoxygenation in myocardial ischemia and hypoxia can cause reversible damage in it, which, with a favorable outcome, disappear without a trace. Excessively late reperfusion and reoxygenation inevitably ends with irreversible damage to the myocardium, which is widely known as a myocardial infarction, and which, together with other complications of cardiac ischemia, can cause disability and death of the patient. In recent years, reperfusion injury of the ischemic heart muscle has been recognized as an independent link in the pathogenesis of myocardial infarction. The mechanisms of this link of pathogenesis have been partially studied in experimental conditions. The phenomena of preconditioning and post-conditioning have been discovered, the effects of which are currently determined fairly reliably. After determining the mechanisms of reperfusion injury of the ischemic myocardium, the search and development of pharmacological agents capable of inducing such a phenomenon as cardioprotection began. In parallel, studies of specific microRNAs that claim to be diagnostic markers are being conducted, as well as the search for drugs that affect the level of their expression is being conducted. The information about the achieved successes in this direction is given.

scholarly journals Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Qun Zheng ◽  
Xiao-Yi Bao ◽  
Peng-Chong Zhu ◽  
Qiang Tong ◽  
Guo-Qing Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Creatine Kinase ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ginsenoside Rb1 ◽  
Creatine Kinase Mb ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group (P<0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study (P<0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.

scholarly journals AMPK/SIRT1 Pathway is Involved in Arctigenin-Mediated Protective Effects Against Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Cheng-Yin Liu ◽  
Yi Zhou ◽  
Tao Chen ◽  
Jing-Chao Lei ◽  
Xue-Jun Jiang
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arctigenin, one of the active ingredients extracted from Great Burdock (Arctium lappa) Achene, has been found to relieve myocardial infarction injury. However, the specific mechanism of Arctigenin against myocardial infarction remains largely unknown. Here, both acute myocardial ischemia-reperfusion injury (AMI/R) rat model and oxygen glucose deprivation (OGD)-induced myocardial cell injury model were constructed to explore the underlying role of AMPK/SIRT1 pathway in Arctigenin-mediated effects. The experimental data in our study demonstrated that Arctigenin ameliorated OGD-mediated cardiomyocytes apoptosis, inflammation and oxidative stress in a dose-dependent manner. Besides, Arctigenin activated AMPK/SIRT1 pathway and downregulated NF-κB phosphorylation in OGD-treated cardiomyocytes, while inhibiting AMPK or SIRT1 by the Compound C (an AMPK inhibitor) or SIRT1-IN-1 (a SIRT1 inhibitor) significantly attenuated Arctigenin-exerted protective effects on cardiomyocytes. In the animal experiments, Arctigenin improved the heart functions and decreased infarct size of the AMI/R-rats, accompanied with downregulated oxidative stress, inflammation and apoptotic levels in the heart tissues. What’s more, Arctigenin enhanced the AMPK/SIRT1 pathway and repressed NF-κB pathway activation. Taken together, our data indicated that Arctigenin reduced cardiomyocytes apoptosis against AMI/R-induced oxidative stress and inflammation at least via AMPK/SIRT1 pathway.

scholarly journals The Rationale of Neprilysin Inhibition in Prevention of Myocardial Ischemia-Reperfusion Injury during ST-Elevation Myocardial Infarction

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2134
Author(s):  
Alessandro Bellis ◽  
Ciro Mauro ◽  
Emanuele Barbato ◽  
Giuseppe Di Gioia ◽  
Daniela Sorriento ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
St Elevation Myocardial Infarction ◽  
St Elevation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

During the last three decades, timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous intervention (pPCI) has allowed amazing improvements in outcomes with a more than halving in 1-year ST-elevation myocardial infarction (STEMI) mortality. However, mortality and left ventricle (LV) remodeling remain substantial in these patients. As such, novel therapeutic interventions are required to reduce myocardial infarction size, preserve LV systolic function, and improve survival in reperfused-STEMI patients. Myocardial ischemia-reperfusion injury (MIRI) prevention represents the main goal to reach in order to reduce STEMI mortality. There is currently no effective therapy for MIRI prevention in STEMI patients. A significant reason for the weak and inconsistent results obtained in this field may be the presence of multiple, partially redundant, mechanisms of cell death during ischemia-reperfusion, whose relative importance may depend on the conditions. Therefore, it is always more recognized that it is important to consider a “multi-targeted cardioprotective therapy”, defined as an additive or synergistic cardioprotective agents or interventions directed to distinct targets with different timing of application (before, during, or after pPCI). Given that some neprilysin (NEP) substrates (natriuretic peptides, angiotensin II, bradykinin, apelins, substance P, and adrenomedullin) exert a cardioprotective effect against ischemia-reperfusion injury, it is conceivable that antagonism of proteolytic activity by this enzyme may be considered in a multi-targeted strategy for MIRI prevention. In this review, by starting from main pathophysiological mechanisms promoting MIRI, we discuss cardioprotective effects of NEP substrates and the potential benefit of NEP pharmacological inhibition in MIRI prevention.

Effect of Ranolazine on Ischemic Myocardium IN Patients With Acute Cardiac Ischemia (RIMINI-Trial): A Randomized Controlled Pilot Trial

2018 ◽  
Vol 24 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Tjark F. Schwemer ◽  
Lukas Radziwolek ◽  
Navina Deutscher ◽  
Nadine Diermann ◽  
Susanne Sehner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Speckle Tracking ◽  
Standard Treatment ◽  
Speckle Tracking Echocardiography ◽  
Pilot Trial ◽  
Ischemic Myocardium ◽  
Cardiac Ischemia ◽  
Study Medication ◽  
Global Strain

Background: Coronary artery disease is the most prevalent manifestation among cardiovascular diseases. Despite modern treatment, risk of ischemic complications in patients with acute coronary syndrome (ACS) remains important. The late Na+ current blocker ranolazine has shown to reduce the risk of recurrent ischemia and worsening of angina in patients with non-ST-segment elevation ACS by possibly improving myocardial perfusion, but up to now no trial has addressed whether this enhanced perfusion also leads to a decrease in ischemic myocardium of patients with ACS. We designed a pilot trial (Reduction of Ischemic Myocardium with Ranolazine-Treatment IN patients with acute myocardial Infarction, ClinicalTrials.gov Identifier: NCT01797484) for feasibility and proof of concept that a 6-week ranolazine add-on therapy would reduce the area of ischemic myocardium in patients with ACS. Methods and Results: The trial was designed in a 2-armed, controlled and randomized way. Twenty participants with unstable angina, proof of acute cardiac ischemia, and myocardial dyskinesia by speckle-tracking echocardiography were included. Ten participants received the study drug ranolazine additionally to standard treatment. The control group received standard treatment without additional study medication. Speckle-tracking echocardiography was performed before coronary intervention, before the first dose of ranolazine, and after 6 weeks of ranolazine treatment. Ranolazine was administered safely during acute myocardial infarction. Speckle-tracking echocardiography proved to be suitable for evaluation of myocardial dyskinesia. Patients receiving ranolazine showed a trend to higher normal fraction of the cumulative global strain than patients in the standard treatment group (15% vs 11%). No major complications relating study medication were observed. Conclusion: In conclusion, in this preliminary hypothesis-driven study, 6-week ranolazine therapy was shown to decrease the area of dyskinetic myocardium in patients with ACS by trend. Global strain rate measurement using speckle-tracking echocardiography can be applied measuring those effects and is, compared to other techniques, safe and harmless. Our data provide a sound basis for a follow-up trial.

scholarly journals Sappanone A Prevents Left Ventricular Dysfunction in a Rat Myocardial Ischemia Reperfusion Injury Model

2020 ◽  
Vol 21 (18) ◽  
pp. 6935
Author(s):  
Woori Jo ◽  
Byung Sun Min ◽  
Hee-Young Yang ◽  
Na-Hye Park ◽  
Kyung-Ku Kang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Injury Model ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Systolic And Diastolic Function

The incidence of myocardial infarction, among the causes of cardiovascular morbidity and mortality, is increasing globally. In this study, left ventricular (LV) dysfunction, including LV systolic and diastolic function, was investigated in a rat myocardial ischemia/reperfusion injury model with echocardiography. The homoisoflavanone sappanone A is known for its anti-inflammatory effects. Using echocardiography, we found that sappanone A administration significantly improved LV systolic and diastolic function in a rat myocardial ischemia/reperfusion injury model, especially in the early phase development of myocardial infarction. Based on myocardial infarct size, serum cardiac marker assay, and histopathological evaluation, sappanone A showed higher efficacy at the doses used in our experiments than curcumin and was evaluated for its potential to improve LV function.

scholarly journals Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5217-5223 ◽  
Author(s):  
Simon F. De Meyer ◽  
Alexander S. Savchenko ◽  
Michael S. Haas ◽  
Daphne Schatzberg ◽  
Michael C. Carroll ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Myocardium ◽  
Wild Type ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion ◽  
Inflammatory Effect

Abstract Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13−/− mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury.

Non-carbonyl Curcuma longa [NCCL] protects the heart from myocardial ischemia/reperfusion injury by reducing endothelial microparticle mediated inflammation in rats

RSC Advances ◽  
2016 ◽  
Vol 6 (60) ◽  
pp. 54938-54948 ◽  
Author(s):  
Amit Manhas ◽  
Dipti Tripathi ◽  
Bharti Biswas ◽  
Hafsa Ahmad ◽  
Dipika Goyal ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Endothelial Cell ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Curcuma Longa ◽  
Ischemia Reperfusion ◽  
Post Myocardial Infarction ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Endothelial cell mediated inflammation flags and mediates the progression of pre and post myocardial infarction.

scholarly journals Acid sensing ion channel 1a is a key mediator of cardiac ischemia-reperfusion injury

2019 ◽  
Author(s):  
Meredith A. Redd ◽  
Sarah E. Scheuer ◽  
Natalie J. Saez ◽  
Ling Gao ◽  
Mark Hicks ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ion Channel ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Genetic Locus ◽  
Cardiac Ischemia ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
And Function

AbstractThe proton-gated acid-sensing ion channel 1a (ASIC1a) is implicated in the injury response to cerebral ischemia but little is known about its role in cardiac ischemia. We provide genetic evidence that ASIC1a is involved in myocardial ischemia-reperfusion injury (IRI) and show that pharmacological inhibition of ASIC1a yields robust cardioprotection in rodent and human models of cardiac ischemia, resulting in improved post-IRI cardiac viability and function. Consistent with a key role for ASIC1a in cardiac ischemia, we show that polymorphisms in the ASIC1 genetic locus are strongly associated with myocardial infarction. Collectively, our data provide compelling evidence that ASIC1a is a key target for cardioprotective drugs to reduce the burden of disease associated with myocardial ischemia.

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