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Background: Catecholamines and β‐adrenergic receptors (β‐ARs) play an important role in the regulation of cardiac tolerance to the impact of ischemia and reperfusion. This systematic review analyzed the molecular mechanisms of the cardioprotective activity of β‐AR ligands. Methods: We performed an electronic search of topical articles using PubMed databases from 1966 to 2023. We cited original in vitro and in vivo studies and review articles that documented the cardioprotective properties of β‐AR agonists and antagonists. Results: The infarct‐reducing effect of β‐AR antagonists did not depend on a decrease in the heart rate. The target for β‐blockers is not only cardiomyocytes but also neutrophils. β1‐blockers (metoprolol, propranolol, timolol) and the selective β2‐AR agonist arformoterol have an infarct‐reducing effect in coronary artery occlusion (CAO) in animals. Antagonists of β1‐ and β2‐АR (metoprolol, propranolol, nadolol, carvedilol, bisoprolol, esmolol) are able to prevent reperfusion cardiac injury. All β‐AR ligands that reduced infarct size are the selective or nonselective β1‐blockers. It was hypothesized that β1‐AR blocking promotes an increase in cardiac tolerance to I/R. The activation of β1‐AR, β2‐AR, and β3‐AR can increase cardiac tolerance to I/R. The cardioprotective effect of β‐AR agonists is mediated via the activation of kinases and reactive oxygen species production. Conclusions: It is unclear why β‐blockers with the similar receptor selectivity have the infarct‐sparing effect while other β‐blockers with the same selectivity do not affect infarct size. What is the molecular mechanism of the infarct‐reducing effect of β‐blockers in reperfusion? Why did in early studies β‐blockers decrease the mortality rate in patients with acute myocardial infarction (AMI) and without reperfusion and in more recent studies β‐blockers had no effect on the mortality rate in patients with AMI and reperfusion? The creation of more effective β‐AR ligands depends on the answers to these questions. [ABSTRACT FROM AUTHOR]

The hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI) is about 6% and has not decreased in recent years. The leading cause of death of these patients is ischemia/reperfusion (I/R) cardiac injury. It is quite obvious that there is an urgent need to create new drugs for the treatment of STEMI based on knowledge about the pathogenesis of I/R cardiac injury, in particular, based on knowledge about the molecular mechanism of ferroptosis. In this study, it was demonstrated that ferroptosis is involved in the development of I/R cardiac injury, antitumor drug-induced cardiomyopathy, diabetic cardiomyopathy, septic cardiomyopathy, and inflammation. There is indirect evidence that ferroptosis participates in stress-induced cardiac injury. The activation of AMPK, PKC, ERK1/2, PI3K, and Akt prevents myocardial ferroptosis. The inhibition of HO-1 alleviates myocardial ferroptosis. The roles of GSK-3β and NOS in the regulation of ferroptosis require further study. The stimulation of Nrf2, STAT3 prevents ferroptosis. The activation of TLR4 and NF-κB promotes ferroptosis of cardiomyocytes. MiR-450b-5p and miR-210-3p can increase the tolerance of cardiomyocytes to hypoxia/reoxygenation through the inhibition of ferroptosis. Circ_0091761 RNA, miR-214-3p, miR-199a-5p, miR-208a/b, miR-375-3p, miR-26b-5p and miR-15a-5p can aggravate myocardial ferroptosis. [ABSTRACT FROM AUTHOR]

Background: The use of percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI) is associated with a mortality rate of 5%–7%. It is clear that there is an urgent need to develop new drugs that can effectively prevent cardiac reperfusion injury. ATP‐sensitive K+ (KATP) channel openers (KCOs) can be classified as such drugs. Results: KCOs prevent irreversible ischemia and reperfusion injury of the heart. KATP channel opening promotes inhibition of apoptosis, necroptosis, pyroptosis, and stimulation of autophagy. KCOs prevent the development of cardiac adverse remodeling and improve cardiac contractility in reperfusion. KCOs exhibit antiarrhythmic properties and prevent the appearance of the no‐reflow phenomenon in animals with coronary artery occlusion and reperfusion. Diabetes mellitus and a cholesterol‐enriched diet abolish the cardioprotective effect of KCOs. Nicorandil, a KCO, attenuates major adverse cardiovascular event and the no‐reflow phenomenon, reduces infarct size, and decreases the incidence of ventricular arrhythmias in patients with acute myocardial infarction. Conclusion: The cardioprotective effect of KCOs is mediated by the opening of mitochondrial KATP (mitoKATP) and sarcolemmal KATP (sarcKATP) channels, triggered free radicals' production, and kinase activation. [ABSTRACT FROM AUTHOR]

The acute myocardial infarction (AMI) and sudden cardiac death (SCD), both associated with acute cardiac ischemia, are one of the leading causes of adult death in economically developed countries. The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine. A study on the cardiovascular effects of chronic hypoxia (CH) may contribute to the development of these methods. Chronic hypoxia exerts both positive and adverse effects. The positive effects are the infarct-reducing, vasoprotective, and antiarrhythmic effects, which can lead to the improvement of cardiac contractility in reperfusion. The adverse effects are pulmonary hypertension and right ventricular hypertrophy. This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion. It is an indepth analysis of the published data on the underlying mechanisms, which can lead to future development of the cardioprotective effect of CH. A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) remains the leading cause of mortality in the world, highlighting an urgent need for the development of novel, more effective approaches for the treatment of AMI. Remote postconditioning (RPost) of the heart could be a useful approach. It was demonstrated that RPost triggers infarct size reduction, improves contractile function of the heart in reperfusion, mitigates apoptosis, and stimulates autophagy in animals with coronary artery occlusion and reperfusion. Endogenous opioid peptides and adenosine could be involved in RPost. It was found that kinases and NO-synthase participate in RPost. KATP channels, MPT pore, and STAT3 could be hypothetical end-effectors of RPost. Metabolic syndrome and old age abolish the cardioprotective effect of RPost in rats. The data on the efficacy of RPost in clinical practice are inconsistent. These data are discussed in the review. [ABSTRACT FROM AUTHOR]

This study investigated the anti-arrhythmic effects from chronic intermittent hypobaric hypoxia (CIHH) and the cellular mechanisms in rats with metabolic syndrome. Male Sprague-Dawley rats were randomly distributed among the control, fructose-fed (fed with 10% fructose in the drinking water to induce metabolic syndrome), CIHH (42 days of hypobaric hypoxia treatment simulating an altitude of 5000 m a.s.l.: PB = 404 mm Hg, [PO.sub.2] = 84 mm Hg, 6 h per day), and the CIHH plus fructose (CIHH-F) groups. In anesthetized rats, the arrhythmia score was determined after 30 min of cardiac ischemia followed by 120 min of reperfusion. Action potentials (AP) were recorded from isolated ventricular papillary muscles. The arrhythmia score was much lower in CIHH-F rats than in the fructose-fed rats. Under basic conditions, AP duration (APD) was significantly shortened in fructose-fed rats, but obviously prolonged in CIHH rats compared with that of the control rats. During ischemia, the AP amplitude, the maximal rate of rise of phase 0, APD, and resting potential, were lower in the control, fructose-fed, and CIHH-F groups, but were not changed in the CIHH rats. The lower AP during ischemia did not recover after washout for the fructose-fed rats. In conclusion, CIHH protects the heart against ischemia-reperfusion induced arrhythmia in rats with metabolic syndrome. This effect of CIHH is possibly related to baseline prolongation of the AP and attenuation of AP reduction during ischemia-reperfusion. Key words: chronic intermittent hypobaric hypoxia, metabolic syndrome, ischemia-reperfusion, papillary muscle, action potential. Cette etude s'est penchee sur l'effet anti-arythmique d'une hypoxie hypobare intermittente chronique (HHIC) et ses mecanismes cellulaires chez des rats atteints du syndrome metabolique. Des rats males Sprague-Dawley ont ete repartis de maniere aleatoire en groupes controle, nourri au fructose (Fruc, nourri avec 10 % de fructose dans l'eau de consommation afin d'induire le syndrome metabolique), HHIC (42 jours d'hypoxie hypobare simulant une altitude de 5000 m : PB 404 mm Hg, [PO.sub.2] = 84 mm Hg, 6 heures par jour), et HHIC et fructose (HHIC-F). L'indice d'arythmie a ete determine chez les rats anesthesies apres 30 min d'ischemie cardiaque suivie d'une reperfusion de 120 min. Les potentiels d'action (PA) ont ete enregistres a partir des muscles ventriculaires papillaires isoles. L'indice d'arythmie etait beaucoup plus faible chez les rats du groupe HHIC-F que ceux du groupe Fruc. En condition de base, la duree du PA (DPA) etait significativement raccourcie chez les rats du groupe Fruc, mais prolongee de maniere evidente chez les rats HHIC comparativement a ceux du groupe controle. Durant l'ischemie, l'amplitude du PA, le taux maximal d'elevation de la phase 0, le DPA et le potentiel au repos etaient plus faibles chez les groupes controle, Fruc et HHIC-F, mais ils etaient inchanges chez les rats du groupe HHIC. Le PA plus faible durant l'ischemie n'etait pas retabli apres un rincage chez les rats Fruc. En conclusion, l'HHIC protege le coeur de l'arythmie induite par ischemie/reperfusion chez les rats atteints du syndrome metabolique. Cet effet de l'HHIC est possiblement relie a la prolongation de la ligne de base du PA et a l'attenuation de la reduction du PA durant l'ischemie-reperfusion. [Traduit par la Redaction] Mots-cles : hypoxie hypobare intermittente chronique, syndrome metabolique, ischemie-reperfusion, muscle papillaire, potentiel d'action., Introduction Metabolic syndrome occurs in 20% of the population worldwide (Brown et al. 2001; Liu et al. 2010; Hanci et al. 2011; Angeloni et al. 2012). The main pathological characteristics [...]

The aim of this study was to investigate whether the mitochondrial permeability transition pore (MPTP) opening was involved in the protective effects of CB2 receptor against ischemia-reperfusion (I-R) injury. For this, isolated perfused rat hearts were subjected to 30 min global ischemia followed by 120 min reperfusion, and left ventricle function was recorded. At the end of reperfusion, the infarct size in the hearts was measured by staining with triphenyltetrazolium chloride. MPTP opening and the mitochondrial membrane potential (Δ[Ψ.sub.m]) were measured by flow cytometry. Western blot analysis of cytochrome c in the mitochondrion and cytosol, as well as ERK1/2 and p-ERK1/2 were performed. Administration of CB2 receptor agonist JWH133 before ischemia significantly improved the recovery of cardiac ventricular function during reperfusion, increased coronary flow, reduced infarct size, prevented the loss of Δ[Ψ.sub.m] and MPTP opening, reduced the release of cytochrome c from mitochondria, and increased levels of p-ERK1/2. These effects of JWH133 were abolished by pretreatment with CB2 receptor antagonist AM630, or ERK1/2 inhibitor PD98059. Furthermore, JWH133 reversed the MPTP opening induced by atractyloside. The protective effect of JWH133 on the heart against I-R injury may be through increased ERK1/2 phosphorylation, inhibiting MPTP opening. Key words: JWH133, CB2 receptor, ischemia-reperfusion, mitochondrial permeability transition pore, ERK1/2, cardioprotection, rat. Afin de determiner si l'ouverture du pore de transition de permeabilite mitochondrial (PTPM) etait implique dans les effets protecteurs du recepteur CB2 envers le dommage d'ischemie-reperfusion (I-R), des cceurs de rats isoles ont ete soumis a une ischemie globale de 30 minutes suivie d'une reperfusion de 120 min, et la fonction ventriculaire gauche a ete enregistree. A la fin de la reperfusion, la taille de l'infarctus cardiaque a ete mesuree par une coloration au chlorure de triphenyltetrazolium, et l'ouverture du PTP et le potentiel membranaire mitochondrial (Δ[Ψ.sub.m]) ont ete mesures par cytometrie de flux. Des analyses par buvardage Western du cytochrome c mitochondrial et cytosolique, de ERK1/2 et de pERK1/2 ont ete realisees. L'administration de JWH133, un agoniste du recepteur CB2, prealablement a l'ischemie ameliorait significativement la recuperation de la fonction cardiaque ventriculaire lors de la reperfusion, augmentait le flux coronaire, reduisait la taille de l'infarctus, prevenait la perte de Δ[Ψ.sub.m] et l'ouverture du PTPM, reduisait la liberation de cytochrome c mitochondrial et augmentait la quantite de pERK1/2. Ces effets du JWH133 etaient abolis par un traitement prealable avec un antagoniste du recepteur CB2, le AM630, ou un inhibiteur de ERK1/2, le PD98059. De plus, le JWH133 pouvait renverser l'ouverture du PTPM induite par l'atractyloside, un agent qui ouvre le PTPM. L'effet protecteur du JWH133 sur le ccur envers le dommage d'I-R pourrait dependre d'une augmentation de la phosphorylation de ERK1/2 afin d'inhiber l'ouverture du PTPM. [Traduit par la Redaction] Mots-cles: WH133, recepteur CB2, ischemie-reperfusion, pore de transition de permeabilite mitochondrial, ERK1/2, cardioprotection, rat., Introduction In recent years the endocannabinoid system has emerged as a new therapeutic target in a variety of disorders associated with inflammation and tissue injury, including those of the cardiovascular [...]