Ischemic preconditioning: Protection against myocardial necrosis and apoptosis

The phenomenon of ischemic preconditioning has been recognized as one of the most potent mechanisms to protect against myocardial ischemic injury. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, reducing infarct size, attenuating the incidence, and severity of reperfusion-induced arrhythmias, and preventing endothelial cell dysfunction. Although the exact mechanism of ischemic preconditioning remains obscure, several reports indicate that this phenomenon may be a form of receptor-mediated cardiac protection and that the underlying intracellular signal transduction pathways involve activation of a number of protein kinases, including protein kinase C, and mitochondrial KATP channels. Apoptosis, a genetically programmed form of cell death, has been associated with cardiomyocyte cell loss in a variety of cardiac pathologies, including cardiac failure and those related to ischemia/reperfusion injury. While ischemic preconditioning significantly reduces DNA fragmentation and apoptotic myocyte death associated with ischemia-reperfusion, the potential mechanisms underlying this effect have not been fully clarified. A comprehensive understanding of these mechanisms and application to clinical scenarios will provide new directions in research and translate this information into new treatment approaches for reducing the extent of ischemia/reperfusion injury

Epithelium-dependent regulation of airways smooth muscle function. A histamine-nitric oxide pathway.

The airway epithelium is responsible for the production of a number of arachidonic acid and non-prostanoid inhibitory factors. Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM-100 microM) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KC1 in the presence or not of 10(-5) Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 microM) on KC1 contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p<0.01). Epithelium removal increased the contraction induced by KC1 (80 mM) and histamine (1 microM) by about 30% (p<0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma

Epithelium-dependent regulation of airways smooth muscle function. A histamine-nitric oxide pathway

The airway epithelium is responsible for the production of a number of arachidonic acid and nonprostanoid inhibitory factors. Epithelium synthesises nitric oxide (NO) which may be important in regulating the function of airways smooth muscles. We studied in vitro the effect of histamine (100 nM100 μ M) which increases the NO release on rabbit airway smooth muscles induced by 80 mM KCl in the presence or not of 10-5 Methylene blue (MB) (inactivator of guanylate cyclase) or N(G)-monomethyl L-arginine (L-NMMA), a NOS inhibitor. All experiments were done in tracheal muscle strips from 28 rabbits with epithelium and after epithelium removal. The additional use of histamine (1 μ M) on KCl contraction induced a relaxation of 10% of the initial contraction. The additional use of L-NMMA decreased the relaxation to 5% of initial contraction. MB rather than L-NMMA increased the contraction significantly (p<0.01). Epithelium removal increased the contraction induced by KCl (80 mM) and histamine (1 μ M) by about 30% (p<0.001). NO release especially from epithelium regulates the airways smooth muscle functions. Damage to the epithelium may contribute to an increase in airways sensitivity, observed in asthma

Rhythm monitoring, success definition, recurrence, and anticoagulation after atrial fibrillation ablation: results from an EHRA survey

Atrial fibrillation (AF) is a major challenge for the healthcare field. Pulmonary vein isolation is the most effective treatment for the maintenance of sinus rhythm. However, clinical endpoints for the procedure vary significantly among studies. There is no consensus on the definition of recurrence and no clear roadmap on how to deal with recurrences after a failed ablation. The purpose of this study was to perform a survey in order to show how clinicians currently approach this knowledge gap. An online survey, supported by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, was conducted between 1 April 2022 and 8 May 2022. An anonymous questionnaire was disseminated via social media and EHRA newsletters, for clinicians to complete. This consisted of 18 multiple-choice questions regarding rhythm monitoring, definitions of a successful ablation, clinical practices after a failed AF ablation, and the continuance of anticoagulation. A total of 107 replies were collected across Europe. Most respondents (82%) perform routine monitoring for AF recurrences after ablation, with 51% of them preferring a long-term monitoring strategy. Cost was reported to have an impact on the choice of monitoring strategy. Self-screening was recommended by most (71%) of the respondents. The combination of absence of symptoms and recorded AF was the definition of success for most (83%) of the respondents. Cessation of anticoagulation after ablation was an option mostly for patients with paroxysmal AF and a low CHA2DS2-VASc score. The majority of physicians perform routine monitoring after AF ablation. For most physicians, the combination of the absence of symptoms and electrocardiographic endpoints defines a successful result after AF ablation

Antithrombotic treatment in patients with atrial fibrillation and acute coronary syndromes: results of the European Heart Rhythm Association survey

The management of an acute coronary syndrome (ACS) in a patient with existing atrial fibrillation (AF) often presents a management dilemma both in the acute phase and post-ACS, since the majority of AF patients will already be receiving oral anticoagulation (OAC) for stroke prevention and will require further antithrombotic treatment to reduce the risk of in-stent thrombosis or recurrent cardiac events. Current practice recommendations are based largely on consensus option as there is limited evidence from randomized controlled trials. Prior to the launch of the new European Heart Rhythm Association (EHRA) consensus document, a survey was undertaken to examine current clinical management of these patients across centres in Europe. Forty-seven centres submitted valid responses, with the majority (70.2%) being university hospitals. This EHRA survey demonstrated overall the management of ACS in AF patients is consistent with the available guidance. Most centres would use triple therapy for a short duration (4 weeks) and predominantly utilize a strategy of OAC (vitamin K antagonist, VKA or non-vitamin K antagonist oral anticoagulant, NOAC) plus aspirin and clopidogrel, followed by dual therapy [(N)OAC plus clopidogrel] until 12 months post-percutaneous coronary intervention, followed by (N)OAC monotherapy indefinitely. Where NOAC was used in combination with antiplatelet(s), the lower dose of the respective NOAC was preferred, in accordance with current recommendations

Effects of pre-procedural remote ischaemic pre-conditioning on the outcomes of elective percutaneous coronary intervention. A systematic review and meta-analysis

AbstractObjectivesTrials of remote ischemic pre-conditioning (RIPC) have suggested this intervention reduces complications of percutaneous coronary intervention and coronary by-pass surgery. The aims of this work were to (i) conduct a systematic review and meta-analysis of the effects of RIPC on cardiac and renal damage in patients undertaking elective percutaneous coronary intervention (PCI); (ii) summarize the results in an evidence-based clinical context.MethodsWe conducted a systematic search of published randomized controlled trials of RIPC for elective PCI up until May 1st, 2015. Studies of peri- or post-ischemic conditioning or emergency PCI were excluded.ResultsNine studies, totalling 1253 patients were included. Compared to control, RIPC groups exhibited reduced peri-procedural myocardial infarction (MI) Odds Ratio (OR) 0.72 (95% CI 0.54 to 0.97, p=0.03); ST-segment deviation OR 0.42 (95% CI 0.28 to 0.63, p<0.0001); major adverse cardiac events (MACE) OR 0.41 (95% CI 0.21 to 0.84, p=0.01); and acute kidney injury (AKI) OR 0.47 (95% CI 0.26 to 0.86, p=0.01), but not mortality OR 1.00 (95% CI 0.27 to 3.73, p=1.00).ConclusionsRIPC is likely to prevent major adverse cardiac and renal events in patients undertaking elective PCI

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study

Aims: Remote ischemic conditioning (RIC) alleviates ischemia–reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection. Methods and results: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p  15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC. Conclusion: RIC evokes “vascular conditioning” likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling

Effect of short-acting beta blocker on the cardiac recovery after cardiopulmonary bypass

The objective of this study was to investigate the effect of beta blocker on cardiac recovery and rhythm during cardiac surgeries. Sixty surgical rheumatic heart disease patients were received esmolol 1 mg/kg or the same volume of saline prior to removal of the aortic clamp. The incidence of cardiac automatic re-beat, ventricular fibrillation after reperfusion, the heart rate after steady re-beat, vasoactive drug use during weaning from bypass, the posterior parallel time and total bypass time were decreased by esmolol treatment. In conclusion: Esmolol has a positive effect on the cardiac recovery in cardiopulmonary bypass surgeries

Acute administration of the olive constituent, oleuropein, combined with ischemic postconditioning increases myocardial protection by modulating oxidative defense

Oleuropein, one of the main polyphenolic constituents of olive, is cardioprotective against ischemia reperfusion injury (IRI). We aimed to assess the cardioprotection afforded by acute administration of oleuropein and to evaluate the underlying mechanism. Importantly, since antioxidant therapies have yielded inconclusive results in attenuating IRI-induced damage on top of conditioning strategies, we investigated whether oleuropein could enhance or imbed the cardioprotective manifestation of ischemic postconditioning (PostC). Oleuropein, given during ischemia as a single intravenous bolus dose reduced the infarct size compared to the control group both in rabbits and mice subjected to myocardial IRI. None of the inhibitors of the cardioprotective pathways, l-NAME, wortmannin and AG490, influence its infarct size limiting effects. Combined oleuropein and PostC cause further limitation of infarct size in comparison with PostC alone in both animal models. Oleuropein did not inhibit the calcium induced mitochondrial permeability transition pore opening in isolated mitochondria and did not increase cGMP production. To provide further insights to the different cardioprotective mechanism of oleuropein, we sought to characterize its anti-inflammatory potential in vivo. Oleuropein, PostC and their combination reduce inflammatory monocytes infiltration into the heart and the circulating monocyte cell population. Oleuropein's mechanism of action involves a direct protective effect on cardiomyocytes since it significantly increased their viability following simulated IRI as compared to non-treated cells. Οleuropein confers additive cardioprotection on top of PostC, via increasing the expression of the transcription factor Nrf-2 and its downstream targets in vivo. In conclusion, acute oleuropein administration during ischemia in combination with PostC provides robust and synergistic cardioprotection in experimental models of IRI by inducing antioxidant defense genes through Nrf-2 axis and independently of the classic cardioprotective signaling pathways (RISK, cGMP/PKG, SAFE)