scholarly journals EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice

2012 ◽  
Vol 96 (1) ◽  
pp. 99-108 ◽  
Author(s):  
Valérie L. Bessi ◽  
Sébastien M. Labbé ◽  
David N. Huynh ◽  
Liliane Ménard ◽  
Christian Jossart ◽  
...  
Keyword(s):  
Myocardial Damage ◽  
Cardioprotective Effects

scholarly journals Peripheral M-choline-reactive systems in the infarct-limited effect implementation of remote ischemic postconditioning during ischemia-reperfusion of myocardium in experiment

2019 ◽  
Vol 16 (4) ◽  
pp. 424-433 ◽  
Author(s):  
F. I. Vismont ◽  
S. N. Chepelev ◽  
P. F. Jushkevich
Keyword(s):  
Clinical Medicine ◽  
Ischemia Reperfusion ◽  
Reactive Systems ◽  
Myocardial Damage ◽  
Ischemic Postconditioning ◽  
Limited Effect ◽  
Systemic Action ◽  
Remote Ischemic Postconditioning ◽  
Old Rats ◽  
Cardioprotective Effects

The search for new effective methods to prevent or mitigate ischemic myocardial damage and the mechanisms for their realization is an important task of modern experimental and clinical medicine. The aim of the study was to elucidate the significance of peripheral M-choline-reactive systems in the realization of the cardioprotective effects of remote ischemic postconditioning (RIPostC) during ischemia-reperfusion of myocardium in experiment. The study revealed that RIPostC has an infarct-limiting effect during ischemia-reperfusion of myocardium in young and old rats, but under the conditions of systemic action of atropine (2 mg/kg), the infarct-limiting effect of RIPostC remained only in old rats. It seems that the activity of peripheral M-choline-reactive systems is important in the mechanisms of realization of the cardioprotective effects of RIPost in young, but not in old rats.

Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats

2007 ◽  
Vol 293 (3) ◽  
pp. H1545-H1552 ◽  
Author(s):  
Yilong Fu ◽  
Zhongjing Wang ◽  
Woei Lee Chen ◽  
Philip K. Moore ◽  
Yi Zhun Zhu
Keyword(s):  
Nitric Oxide ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Tween 80 ◽  
Vehicle Group ◽  
Lv Function ◽  
Cardioprotective Effects ◽  
Cox 2

In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg·kg−1·day−1), and NO-aspirin (56 mg·kg−1·day−1). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle ( n = 23), aspirin ( n = 22), and NO-aspirin groups ( n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 ± 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated groups, 36.7 ± 1.8 and 22.9 ± 4.3%, respectively (both P < 0.05 compared with vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemiareperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with NG-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. l-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion.

Selective inhibition of p38α MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury

2006 ◽  
Vol 291 (4) ◽  
pp. H1972-H1977 ◽  
Author(s):  
Zhihe Li ◽  
Jing Ying Ma ◽  
Irene Kerr ◽  
Sarvajit Chakravarty ◽  
Sundeep Dugar ◽  
...  
Keyword(s):  
Cardiac Function ◽  
P38 Mapk ◽  
Rat Model ◽  
Myocardial Injury ◽  
Myocardial Damage ◽  
Cardiomyocyte Apoptosis ◽  
Ang Ii ◽  
P38α Mapk ◽  
Cardioprotective Effects ◽  
Mapk Inhibitor

p38 MAPK is activated during heart diseases that might associate with myocardial damage and deterioration of cardiac function. In a rat model of myocardial injury, we have investigated cardioprotective effects of the inhibition of p38 MAPK using a novel, orally available p38α MAPK inhibitor. Rats were treated with Nω-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg−1·day−1) in drinking water plus 1% salt for 14 days and ANG II (0.5 mg·kg−1·day−1) for 3 days. A selective p38α MAPK inhibitor, SD-282 (60 mg/kg), was administrated orally, twice a day for 4 days, starting 1 day before ANG II administration. The cardioprotective effects of p38α MAPK inhibition were evaluated by improvement of cardiac function, reduction of inflammatory cell infiltration, and cardiomyocyte apoptosis. SD-282 significantly improved cardiac function indicated by increasing stroke volume, cardiac output, ejection fraction, and stroke work and significantly decreasing arterial elastance. SD-282 also significantly reduced macrophage infiltration as judged by reduction of a specific marker, ED-1-positive staining cells ( P < 0.05) in the myocardium. Furthermore, cardiomyocyte apoptosis as indicated by caspase-3 immunohistochemical staining was abolished by SD-282, and this effect may contribute to the reduction of myocardial damage evaluated by imaging analysis ( P < 0.05 in both cases). Data suggest that p38α MAPK may play a critical role in the pathogenesis of cardiac dysfunction. Inhibition of p38α MAPK may be used as a novel cardioprotective strategy in attenuation of inflammatory response and deterioration of cardiac function that occurs in acute cardiovascular disease such as myocardial infarction.

scholarly journals Pharmacological screening of substances with cardioprotective effect in the group of 3-oxypyridine derivatives

2018 ◽  
Vol 4 (2) ◽  
pp. 125-131
Author(s):  
Lyudmila M. Danilenko ◽  
Sophiya Ya. Skachilova ◽  
Sergey V. Nadezhdin ◽  
Alena Timokhina ◽  
Olesya V. Shcheblykina ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Troponin I ◽  
Biochemical Marker ◽  
White Blood Cells ◽  
Myocardial Damage ◽  
Cardioprotective Effect ◽  
Lead Compound ◽  
Blood Leukocytes ◽  
Cardioprotective Effects

Introduction: The search for new compounds with antihypoxic and cardioprotective effects among 3-oxypyridine derivatives is promising. Research objectives: To study the anti-hypoxic and cardioprotective effects of 3-oxypyridine derivatives. Materials and methods: The search for compounds with an antihypoxic effect was carried out on blood leukocytes of rats in in vitro. To simulate hypoxia, Oil for Tissue Culture (SAGE) was used, 500 µl of which was applied into wells over a growth medium in order to block gas exchange. The cardioprotective effect of 3-oxypyridine derivatives was studied in the model of coronary-occlusive myocardial infarction (30 minutes of ischemia, 90 minutes of reperfusion). The level of troponin I (Tn I) was determined as a biochemical marker of myocardial damage. Results and discussion: In the in vitro experiments, when culting white blood cells, the lead compound in the group of 3-oxypyridine derivatives was identified under code LKhT 21–16, which increases the number of viable cells in the presence of hypoxia, surpassing the reference drugs. When confirming the chemical structure of the lead compound, LHT 21–16, a high sensitivity of the NMR spectroscopy method was revealed. In studying the cardioprotective activity in the model of coronary-occlusive myocardial infarction compound LHT 21–16 exerted a marked cardioprotective effect when reducing the size of the necrotic zone and the level of biochemical marker Tn I. Conclusions: 3-oxypiridine derivatives have antihypoxic and cardioprotective effects, which shows in a high number of surviving cells in the presence of hypoxia in the in vitro model, a reduced size of the necrotic zone and a reduced level of Tn I in the coronary-occlusive myocardial infarction.

scholarly journals Pharmacodynamics Interaction of Quercetin and Captopril on Doxorubicin Induced Myocardial Toxic Rats

2021 ◽  
Vol 12 (3) ◽  
pp. 3002-3011
Keyword(s):  
Cardiovascular Disease ◽  
Single Dose ◽  
Qt Interval ◽  
Ace Inhibitor ◽  
Myocardial Damage ◽  
Antagonistic Effect ◽  
Marker Enzymes ◽  
Antioxidant Mechanism ◽  
St Segment ◽  
Cardioprotective Effects

Captopril (CAP), an ACE inhibitor, is widely used in the therapy of cardiovascular disease. Quercetin (QUE), a plant-derived flavonol that exerts cardioprotective activity through its antioxidant mechanism. A combination of CAP and QUE may produce synergistic or antagonistic cardioprotective effects. Therefore, the present study was designed to evaluate the pharmacodynamics interaction of QUE and CAP in Doxorubicin (Dox) induced oxidative myocardial damage in rats. Rats were pretreated with normal saline, QUE (10 mg/kg), and CAP (30 mg/kg) alone and in combination orally for 14 days. On the 14th day of treatment, rats were injected with Dox (10mg/kg single dose i.p) for the induction of myocardial damage. There was a substantial fall and rise in activities of marker enzymes such as CK-MB, LDH, AST, and ALT in serum and elevation of ST-segment, increased QT interval, and HR upon Dox administration. Pretreatment with QUE and CAP alone significantly restored the above parameters. But, the Concomitant pretreatment with QUE and CAP was found to be less significantly restored the Dox-induced alterations. The present study suggests that concomitant pretreatment with CAP and QUE could attenuate cardiovascular protection than that of alone pretreatment. It may be due to the antagonistic effect between the two drugs.

scholarly journals Pharmacological Inhibition of S-Nitrosoglutathione Reductase Reduces Cardiac Damage Induced by Ischemia–Reperfusion

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 555
Author(s):  
Oscar Arriagada Castillo ◽  
Gustavo Herrera ◽  
Carlos Manriquez ◽  
Andrea F. Rojas ◽  
Daniel R. González
Keyword(s):  
Ventricular Function ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protein S ◽  
Isolated Rat Heart ◽  
Cardioprotective Effect ◽  
Mitochondrial Proteins ◽  
Cardiac Damage ◽  
Pharmacological Inhibition ◽  
Cardioprotective Effects

The cardioprotective effects of nitric oxide (NO) have been described through S-nitrosylation of several important proteins in the mitochondria of the cardiomyocyte. S-nitrosoglutathione reductase (GSNOR) is an enzyme involved in the metabolism of S-nitrosothiols by producing denitrosylation, thus limiting the cardioprotective effect of NO. The effect of GSNOR inhibition on the damage by cardiac ischemia–reperfusion is still unclear. We tested the hypothesis that pharmacological inhibition of GSNOR promotes cardioprotection by increasing the levels of protein S-nitrosylation. In a model of ischemia–reperfusion in isolated rat heart, the effect of a GSNOR inhibitor, 5-chloro-3-(2-[4-ethoxyphenyl) (ethyl) amino]-2-oxoethyl)-1H-indole-2-carboxylic acid (C2), was investigated. Ventricular function and hemodynamics were determined, in addition to tissue damage and S-nitrosylation of mitochondrial proteins. Hearts treated with C2 showed a lower release of myocardial damage marker creatine kinase and a reduction in the infarcted area. It also improved post-ischemia ventricular function compared to controls. These results were associated with increasing protein S-nitrosylation, specifically of the mitochondrial complexes III and V. The pharmacological inhibition of GSNOR showed a concentration-dependent cardioprotective effect, being observed in functional parameters and myocardial damage, which was maximal at 1 µmol/L, associated with increased S-nitrosylation of mitochondrial proteins. These data suggest that GSNOR is an interesting pharmacological target for cardiac reperfusion injury.

scholarly journals The investigation of cardioprotective effects of novel necroptosis inhibitors - necrosulfonamide and necrostatin-1s in the rat model of isolated perfused rat heart

2016 ◽  
Vol 15 (3) ◽  
pp. 81-85
Author(s):  
Yu. V. Dmitriev ◽  
S. M. Minasian ◽  
E. A. Demchenko ◽  
V. K. Bayrasheva ◽  
M. M. Galagudza
Keyword(s):  
Unsolved Problem ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Myocardial Damage ◽  
Global Ischemia ◽  
Myocardial Cells ◽  
Pharmacological Agents ◽  
Low Toxicity ◽  
Cardioprotective Effects ◽  
Best Parameters

Minimization of irreversible myocardial damage after ischemia-reperfusion episode remains valid and unsolved problem. Among of many pharmacological agents have been effective in experimental studies, only a few of them are evidence of its efficacy in clinical trials. This is largely explained by the mechanism of action of these compounds, aimed primarily at preventing reperfusion injury, and do not affect myocardial cells subjected to prolonged ischemia without reperfusion. In recent years, the interest of researchers confined to the mechanisms of programmed necrosis or necroptosis, which morphologically has no different to necrosis, but has molecular targets for suppression. In this paper, on the model of global ischemia-reperfusion in rats we have studied cardioprotective effects of high-activity and low-toxicity necroptosis inhibitors - necrosulfonamide and necrostatin-1s. We demonstrated the infarct-limiting effect of these compounds, as well as the best parameters of intracardiac hemodynamics after an episode of global ischemia-reperfusion. We believe these compounds are interesting for further preclinical studies.

scholarly journals Cardiovascular complications in patients with cancer: focus on anthracycline-induced cardiotoxicity

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
I. T. Murkamilov ◽  
K. A. Aitbaev ◽  
V. V. Fomin ◽  
I. O. Kudaibergenova ◽  
F. A. Yusupov ◽  
...  
Keyword(s):  
Risk Factors ◽  
Late Onset ◽  
Beta Blockers ◽  
Myocardial Dysfunction ◽  
Myocardial Damage ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Type I ◽  
Patients With Cancer ◽  
Cardioprotective Effects

The article describes prevalence and risk factors of cardiovascular in patients with cancer. The problems of anthracycline-induced cardiotoxicity, the deleterious effects of doxorubicin on the heart, as well as the cardioprotective effects of beta-blockers and agents acting on the renin-angiotensin-aldosterone system pathway are discussed. By cardiotoxicity is implied the development of various adverse cardiovascular events against the background of drug therapy for cancer patients. Depending on the severity of myocardial damage, there are type I (anthracycline-mediated cardiotoxicity, myocardial damage is irreversible) and type II (trastuzumab-mediated cardiotoxicity, myocardial dysfunction is reversible) cardiotoxicity. Anthracycline-induced cardiotoxicity, in turn, is divided into acute, early-onset chronic and late-onset chronic. At the same time, the main mechanisms of anthracycline cytotoxicity in relation to healthy cardiomyocytes are stimulation of intracellular oxidative stress, a decrease in reduced glutathione concentration, inhibition of cell redox potential, and a change in iron metabolism. The article discusses in detail the risk factors (age, hypertension, diabetes, asymptomatic left ventricular dysfunction, documented cardiovascular diseases, heart failure, etc.), as well as the mechanisms and treatment of anthracycline-mediated cardiotoxicity.

scholarly journals Changes of parameters of carbonyl-oxidative stress in rats with experimental myocardial ischemia under the influence of doxycycline

2018 ◽  
Vol 76 (2) ◽  
pp. 6-12
Author(s):  
V. Tkachenko ◽  
A. Shevtsova
Keyword(s):  
Oxidative Stress ◽  
Heart Diseases ◽  
Myocardial Damage ◽  
Oxidative Modification ◽  
Biochemical Mechanisms ◽  
Cardioprotective Effects ◽  
Experimental Myocardial Ischemia ◽  
Phenol Ring ◽  
Active Substances ◽  
Cardioprotective Action

Heart diseases, especially acute myocardial infarction (AMI), belong to the most severe illnesses that often lead to death. Despite a large number of studies, the biochemical mechanisms of AMI and post-infarction myocardial remodeling are poorly understood. Carbonyl-oxidative stress (COS) is one of the more important triggers of the post-infarction complications in these patients, so the neutralizing of the intermediates and final products of COS are a perspective direction in the treatment of AMI. Flavonoide antioxidants as well as inhibitors of carbonylation and glycation of proteins shown the cardioprotective effects but their use have some limitations. Recently, new studies have appeared concerning the cardioprotective action of the doxycycline (DC). This tetracycline antibiotic can inhibit matrix metalloproteinases and proteolysis in extracellular matrix. At the same time, the presence of a multiple-substituted phenol ring can provide the ability of DC to neutralize free radicals, so we hypothesized that it can inhibit the COS. This article compares the effects of small (4,2 mg/kg) and of large (16.8 mg/kg) doses of DC with the effects of classical antioxidants, corvitin and aminoguanidine. The COS-markers and activity of antioxidant enzymes were determined in the blood and subcellular heart fractions of the rats with pituitrin-isoproterenol-induced myocardial damage. It has been established that DC exhibits cardioprotective properties, reducing the formation of products of carbonyl and oxidative modification of biomolecules TBA-active substances, fluorescent end products of glycation (fAGE), aldehyde phenylhydrazones (AFH) and ketone phenylhydrazones (CPH), and a more pronounced effect was shown for the low doses of this drug. Simultaneously, the DC activates enzymes of antioxidant protection, first of all, glutathione peroxidase. Effects of small doses of DC are comparable or exceed the action of aminoguanidine and corvitin, so DC can be useful in the treatment of postinfarction heart failure.

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