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 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.

scholarly journals Revisiting the Cardioprotective Effects of Acetylcholine Receptor Activation against Myocardial Ischemia/Reperfusion Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2466 ◽  
Author(s):  
Kannaporn Intachai ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn ◽  
Krekwit Shinlapawittayatorn
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Receptor Activation ◽  
Vagal Activity ◽  
Ischemic Conditioning ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Ach Receptors

Acute myocardial infarction (AMI) is the most common cause of acute myocardial injury and its most clinically significant form. The most effective treatment for AMI is to restore an adequate coronary blood flow to the ischemic myocardium as quickly as possible. However, reperfusion of an ischemic region can induce cardiomyocyte death, a phenomenon termed “myocardial ischemia/reperfusion (I/R) injury”. Disruption of cardiac parasympathetic (vagal) activity is a common hallmark of a variety of cardiovascular diseases including AMI. Experimental studies have shown that increased vagal activity exerts cardioprotective effects against myocardial I/R injury. In addition, acetylcholine (ACh), the principle cardiac vagal neurotransmitter, has been shown to replicate the cardioprotective effects of cardiac ischemic conditioning. Moreover, studies have shown that cardiomyocytes can synthesize and secrete ACh, which gives further evidence concerning the importance of the non-neuronal cholinergic signaling cascades. This suggests that the activation of ACh receptors is involved in cardioprotection against myocardial I/R injury. There are two types of ACh receptors (AChRs), namely muscarinic and nicotinic receptors (mAChRs and nAChRs, respectively). However, the effects of AChRs activation in cardioprotection during myocardial I/R are still not fully understood. In this review, we summarize the evidence suggesting the association between AChRs activation with both electrical and pharmacological interventions and the cardioprotection during myocardial I/R, as well as outline potential mechanisms underlying these cardioprotective effects.

Activation of estrogen receptor-α protects the in vivo rabbit heart from ischemia-reperfusion injury

2005 ◽  
Vol 289 (5) ◽  
pp. H2039-H2047 ◽  
Author(s):  
Erin A. Booth ◽  
Nabeel R. Obeid ◽  
Benedict R. Lucchesi
Keyword(s):  
Estrogen Receptor ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rabbit Model ◽  
Experimental Studies ◽  
Cardioprotective Effects

The estrogen receptor (ER) mediates estrogenic activity in a variety of organs, including those in the reproductive, cardiovascular, immune, and central nervous systems. Experimental studies have demonstrated that 17β-estradiol (E2) protects the heart from ischemia-reperfusion injury. Two estrogen receptors, ERα and ERβ, mediate the actions of estrogen; however, it is not certain which ER mediates the cardioprotective effects of E2. In the present study, the ER-selective agonists 4,4′,4′′-[4-propyl-(1 H)-pyrazole-1,3,5-triyl]tris-phenol (PPT; ERα) and 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ERβ) were assessed for their cardioprotective potential in an in vivo rabbit model of ischemia-reperfusion injury. Anesthetized female rabbits were administered PPT (3 mg/kg), DPN (3 mg/kg), E2 (20 μg/rabbit), or vehicle intravenously 30 min before a 30-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Acute treatment with E2 (17.7 ± 2.9%; P < 0.001) and PPT (18.1 ± 2.9%; P < 0.001), but not DPN (45.3 ± 2.4%) significantly decreased infarct size as a percent of area at risk compared with vehicle (45.3 ± 2.4%). Coadministration of PPT or E2 with the ER antagonist ICI-182,780 limited the infarct size-sparing effect of the compounds (43.8 ± 6.6% and 40.6 ± 5.7% respectively, expressed as a percentage of risk region). PPT reduced the release of cardiac-specific troponin-I and reduced the tissue deposition of the membrane attack complex and C-reactive protein similar to that of E2. The results indicate that activation of ERα, but not ERβ, is required for the observed cardioprotective effects of E2.

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.

scholarly journals Pharmacological Conditioning of the Heart: An Update on Experimental Developments and Clinical Implications

2021 ◽  
Vol 22 (5) ◽  
pp. 2519
Author(s):  
Sebastian Roth ◽  
Carolin Torregroza ◽  
Katharina Feige ◽  
Benedikt Preckel ◽  
Markus W. Hollmann ◽  
...  
Keyword(s):  
Clinical Evidence ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Basic Research ◽  
Clinical Implications ◽  
Extensive Literature ◽  
Pharmacological Agents ◽  
New Developments ◽  
Experimental Protocols ◽  
Myocardial Ischemia Reperfusion

The aim of pharmacological conditioning is to protect the heart against myocardial ischemia-reperfusion (I/R) injury and its consequences. There is extensive literature that reports a multitude of different cardioprotective signaling molecules and mechanisms in diverse experimental protocols. Several pharmacological agents have been evaluated in terms of myocardial I/R injury. While results from experimental studies are immensely encouraging, translation into the clinical setting remains unsatisfactory. This narrative review wants to focus on two aspects: (1) give a comprehensive update on new developments of pharmacological conditioning in the experimental setting concentrating on recent literature of the last two years and (2) briefly summarize clinical evidence of these cardioprotective substances in the perioperative setting highlighting their clinical implications. By directly opposing each pharmacological agent regarding its recent experimental knowledge and most important available clinical data, a clear overview is given demonstrating the remaining gap between basic research and clinical practice. Finally, future perspectives are given on how we might overcome the limited translatability in the field of pharmacological conditioning.

scholarly journals Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated fromRhizoma Chuanxiong): Roles and Mechanisms

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ming Guo ◽  
Yue Liu ◽  
Dazhuo Shi
Keyword(s):  
Cardiovascular System ◽  
Active Component ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Potential ◽  
Ischemia Reperfusion ◽  
Chinese Herb ◽  
Experimental Studies ◽  
Rhizoma Chuanxiong ◽  
Cardioprotective Effects ◽  
Pharmacologically Active

Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herbRhizoma Chuanxiong(Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP’s clinical use.

scholarly journals Comparison of the Effects of Ketamine-Dexmedetomidine and Sevoflurane-Sufentanil Anesthesia on Cardiac Biomarkers After Cardiac Surgery: An Observational Study

2012 ◽  
pp. 63-72 ◽  
Author(s):  
H. ŘÍHA ◽  
T. KOTULÁK ◽  
A. BŘEZINA ◽  
L. HESS ◽  
P. KRAMÁŘ ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Observational Study ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Artery Bypass ◽  
Experimental Studies ◽  
Cardiac Troponin I ◽  
Cardiac Biomarkers ◽  
Cardioprotective Effects

Inhalational anesthetics have demonstrated cardioprotective effects against myocardial ischemia-reperfusion injury. Clinical studies in cardiac surgery have supported these findings, although not with the consistency demonstrated in experimental studies. Recent investigations have questioned the advantages of inhalational over intravenous anesthetics with respect to cardiac protection. Ketamine has been shown to be comparable with sufentanil, and has even demonstrated anti-inflammatory properties. Dexmedetomidine has been established as a sedative/anesthetic drug with analgesic properties, and has also demonstrated myocardial protective effects. In this retrospective observational study, the influence of ketamine-dexmedetomidine-based anesthesia (KET-DEX group; n=17) on the release of cardiac biomarkers was compared with that of sevoflurane-sufentanil-based anesthesia (SEVO group; n=21) in patients undergoing elective coronary artery bypass grafting. Compared with the SEVO group, the KET-DEX group exhibited significantly reduced cardiac troponin I (2.22±1.73 vs. 3.63±2.37 µg/l; P=0.02) and myocardial fraction of creatine kinase (CK-MB) levels (12.4±10.4 vs. 20.3±11.2 µg/l; P=0.01) on the morning of the first postoperative day. Furthermore, cardiac troponin I release, evaluated as the area under the curve, was significantly reduced in the KET-DEX group (32.1±20.1 vs. 50.6±23.2; P=0.01). These results demonstrate the cardioprotective effects of ketamine-dexmedetomidine anesthesia compared with those of sevoflurane-sufentanil anesthesia.

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.

Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation

2007 ◽  
Vol 292 (5) ◽  
pp. C1583-C1590 ◽  
Author(s):  
Marko Ljubkovic ◽  
Yasushi Mio ◽  
Jasna Marinovic ◽  
Anna Stadnicka ◽  
David C. Warltier ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Atp Synthesis ◽  
Mitochondrial Uncoupling ◽  
Pharmacological Agents ◽  
Mitochondrial Redox State ◽  
Cardioprotective Effects ◽  
Isoflurane Treatment ◽  
Mild Uncoupling

Ischemic cardiac injury can be substantially alleviated by exposing the heart to pharmacological agents such as volatile anesthetics before occurrence of ischemia-reperfusion. A hallmark of this preconditioning phenomenon is its memory, when cardioprotective effects persist even after removal of preconditioning stimulus. Since numerous studies pinpoint mitochondria as crucial players in protective pathways of preconditioning, the aim of this study was to investigate the effects of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype. Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state, was elevated to 195 ± 16% of baseline upon isoflurane application in intact cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane treatment also elicited partial dissipation of mitochondrial transmembrane potential, which remained depolarized even after anesthetic withdrawal (tetramethylrhodamine fluorescence intensity declined to 83 ± 3 and 81 ± 7% of baseline during isoflurane exposure and washout, respectively). Mild uncoupling, with preserved ATP synthesis, was also detected in mitochondria that were isolated from animals that had been previously preconditioned by isoflurane in vivo, revealing its memory nature. These mitochondria, after exposure to hypoxia and reoxygenation, exhibited better preserved respiration and ATP synthesis compared with mitochondria from nonpreconditioned animals. Partial mitochondrial depolarization was paralleled by a diminished Ca2+ uptake into isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2 fluorescence when mitochondria were challenged with increased Ca2+ (180 ± 24 vs. 258 ± 14% for the control). In conclusion, isoflurane preconditioning elicits partial mitochondrial uncoupling and reduces mitochondrial Ca2+ uptake. These effects are likely to reduce the extent of the mitochondrial damage after the hypoxic stress.

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