Role of Atrial Natriuretic Peptide in Oxytocin Induced Cardioprotection

Background The purpose of this study was to determine whether endogenous atrial natriuretic peptide (ANP) contributes to the protective effect of neurohypophysial hormone oxytocin (OT) in heart preconditioning. Methods Sprague-Dawley male rats were subjected to 25 min regional ischaemia and 120 min reperfusion and were divided into eight groups. Oxytocin or an equivalent volume of saline was administrated intraperitoneally, 30 min before ischaemia. The OT receptor antagonist (atosiban), ANP receptor antagonist (anantin) and nitric oxide synthase inhibitor (L-NAME) were injected 10 min before OT. In other groups, atosiban, anantin and L-NAME were only administered 40 min prior to ischaemia. Results Compared with the ischaemia/reperfusion group (I/R), alterations in infarct size, biochemical parameters LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB), MDA (malondialdehyde) plasma levels] and severity of ventricular arrhythmia due to I/R injury were attenuated and VF was abolished by OT treatment. These OT effects were eliminated by OT and ANP receptor blockers and nitric oxide synthase inhibitor, but anantin did not reverse the effect of OT in lipid peroxidation. Conclusions These findings demonstrate an important contributory role of ANP in the OT induced protection in myocardial ischaemia reperfusion. OT also reduced lipid peroxidation with a NO-dependent mechanism

The Role of Oxytocin on Cardiac Ischemia-ReperfusionInduced Oxidative Stress in Rats

Abstract Introduction: Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. Reactive oxygen species (ROS) can play an important role in the pathogenesis of cardiovascular diseases. The present study aimed at investigating whether administration of oxytocin ameliorates oxidative stress induced by experimental myocardial infarction in rats. Materials and Methods: Cardiac ischemia-reperfusion (I/R) was induced by occlusion of left main coronary artery of rats for 25 min, followed by a period of reperfusion for 2h. OT at doses of 0.0001-1 µg was administered intraperitoneally 30 min prior to ischemia. Following reperfusion, blood samples were taken for measuring the plasma MDA levels, as an index of lipid peroxidation. Results: We observed a dose-dependent association between dose of oxytocin and plasma MDA. Oxytocin 0.01µg significantly reduced MDA levels as compared to control group. Blockade of specific OT receptors by atosiban attenuated the anti-oxidative effect of OT. The MDA level in the L-NAME and atropine groups were higher than those in the OT group and reach to control group, whereas the MDA levels in the anantin group were same as OT group and significantly lower than those in the control group. Conclusions: Oxytocin has a beneficial effect, mediated by NO and Ach, on cardiac tissue against oxidative damage due to I/R, suggesting that oxytocin can be used to tissue protection against oxidative stress

chronic sleep deprevation and ventricular arrhythmias: effect of symphatic nervous system

Introduction: We assessed the effect of chronic sleep deprivation on incidence of ischemia/reperfusion-induced ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) and the role of the sympathetic nervous system in this respect. Material and methods: Rats were randomly divided into four groups; 1) ischemia/reperfusion group (IR): 30 minutes ischemia followed by 60 minutes reperfusion was induced, 2) control group (CON): rats has been placed in large multiple platforms for 72h prior to ischemia and reperfusion, 3) Chronic sleep deprivation group( SD): 72h sleep deprivation was induced by using small  multiple platform prior to ischemia and reperfusion, 4) Sympathectomy group (SYM): chemical sympathectomy was done 24h before to chronic sleep deprivation and then underwent ischemia and reperfusion. The heart isolated and perfused by langendorff apparatus. After thoracotomy and aorta cannulation, the hearts perfused in the langendorff apparatus using krebs-Henseleit buffer. Hearts were allowed to recovery for 15 min. After recovery period, 15 minutes was considered as baseline prior to 30 minutes ischemia followed by 60 minutes reperfusion.Tow thin stainless stell electrodes fixed on the ventricular apex and right atrium for recording the lead II of electrocardiogram (ECG).Results: There were no significant differences between heart rates between groups, and ventricular tachycardia significantly increased in chronic sleep deprivation group As compared with IR group in ischemia period. Sympathectomy significantly reduced ventricular tachycardia incidence when compared with SD. There is no difference in incidence of ventricular tachycardia between control group and IR group. The incidence of ventricular fibrillation during early reperfusion was significantly augmented (P<0.05) in sleep deprivation group as compared with IR group and Sympathectomy significantly could reverse ventricular fibrillation incidence to IR group level as compared with SD group (P<0.05).Conclusion: Induction of 72 h sleep deprivation prior to ischemia and reperfusion increased the probability of ventricular tachycardia and ventricular fibrillation occurrence during ischemia and reperfusion and chemical sympathectomy could eliminate this effect

The role of central oxytocin in stress-induced cardioprotection in ischemic-reperfused heart model

Background and purpose: There is growing evidence that stress contributes to cardiovascular disease and triggers the release of oxytocin. Moreover previous studies confirmed oxytocin mimics the protection associated with ischemic preconditioning. The present study was aimed to assess the possible cardioprotective effects of the centrally released oxytocin in response to stress and intracerebroventricular (i.c.v.) administration of exogenous oxytocin in ischemic-reperfused isolated rat heart. Methods and subjects: Rats were divided in two main groups and all of them were subjected to i.c.v. infusion of vehicle or drugs: unstressed rats control: vehicle, oxytocin (OT; 100 ng/5 mu l), atosiban (ATO; 4.3 mu g/5 mu l) as oxytocin antagonist, ATO + OT] and stressed rats St: stress, OT + St, ATO + St]. After anesthesia, hearts were isolated and subjected to 30 min regional ischemia and 60 min reperfusion (IR). Acute stress protocol included swimming for 10 min before anesthesia. Myocardial function, infarct size, coronary flow, ventricular arrhythmia, and biochemical parameters such as creatine kinase and lactate dehydrogenase were measured. Ischemia-induced ventricular arrhythmias were counted during the occlusion period. Results: The plasma levels of oxytocin and corticosterone were significantly elevated by stress. Unexpectedly hearts of stressed rats showed a marked depression of IR injury compared to control group. I.c.v. infusion of oxytocin mimicked the cardioprotective effects of stress, yet did not elevate plasma oxytocin level. The protective effects of both stress and i.c.v. oxytocin were blocked by i.c.v. oxytocin antagonist. Conclusions: These findings suggest that i.c.v. infusion of exogenous oxytocin and centrally released endogenous oxytocin in response to stress could play a role in induction of a preconditioning effect in ischemic-reperfused rat heart via brain receptors. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved

Does increased Nitric Oxide production and oxidative stress due to high fat diet affect cardiac function after myocardial infarction?

Background &Objectives: High fat (HF) diet by affecting the oxidative stress and nitric oxide (NO) production may lead to different effects on function of the heart after myocardial infarction (MI). In the present study we aimed to address the hypothesis that high release of NO by activated macrophages affects LV function after MI.Methods: The animals were randomly divided into four groups comprising each of 10 rats: 1) Sham; 2) MI; 3) Sham+ HF diet; 4) MI+ HF diet. Animals fed with HF diet 30 days before sham and MI surgery. MI was induced by permanent ligation of left anterior descending coronary artery (LAD). Nitric oxide (NO) production of peritoneal macrophages, the concentrations of MDA in the heart and the infarct size were measured.Results: Our study indicated that HF has adverse effects on myocardium and it may increase NO production as well as oxidative stress, resulting in augmentation of infarct size.Conclusion: Our results add to our knowledge that HF diet was associated with overproduction of NO by peritoneal macrophages and ROS that lead to development of infarct size and adverse remodeling

What Happened to Simulation-Based Education in Outpatient Setting in The 21st Century: A Scoping Review

Introduction: Simulation-based education (SBE) is an instructional approach that aims to accurately recreate real-life scenarios and engage learners in the practical application of lesson content. By replicating critical elements of clinical situations, SBE facilitates a deeper understanding and better preparation for managing such conditions in actual clinical practice. SBE offers promising prospects for improving medical education and patient care in various settings,such as outpatient clinics. Therefore, this scoping review aims to determine to what extent the most effective components and standards of the simulation have been considered in outpatient education.Methods: The present scoping review adheres to the guidelines outlined in the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMAScR) checklist” and the “Joanna Briggs Institute (JBI) Reviewers’ Manual”. This review focused on articles that specifically focused on the use of simulation in outpatient education. Google Scholar, PubMed, Scopus, Embase, and ERIC were searched for keywords related to simulation, ambulatory care, outpatient clinics, and medical education from January 1, 2001, to August 12, 2023.Results: The search indicated 513 articles, which were narrowed down by title and abstract relatedness. Twenty-nine articles entered the study’s second phase, and after reviewing their full text, nine articles that explicitly reported simulation use in outpatient education remained. Based on the findings of eligible articles, the ten most frequent components of SBE that should be considered and followed discussed. These features were training facilitators, pre-briefing sessions, the type of simulation techniques, the site of simulation participation, the simulation duration, unit of participation, extent of direct participation, Simulation fidelity, feedback, and debriefing and reflection.Conclusion: SBE is a contemporary method of practical training for medical students that involves realistic modeling or simulation of clinical situations. It enhances learning effectiveness andprovides a safe, educational atmosphere for teaching and learning. Designing simulations adhering to established standards and carefully considering essential components improves efficiencyand effectiveness

Mg2+ protects adult beating cardiomyocytes against ischaemia

Although Mg(2+) reduces infarct size in whole heart models of ischaemia/reperfusion, the cardioprotective effect of Mg(2+) at the cellular level is still a controversial issue. Therefore, we tested whether Mg(2+) protects cardiomyocytes against ischaemia. To accomplish this aim we used an experimental model of ischaemia that utilises single beating adult cardiomyocytes in which oxygen tension is tightly regulated without the use of oxygen scavengers or metabolic inhibitors. Taking all these into consideration, this model is probably closer to in vivo conditions than the majority of previously published cellular models of ischaemia. We found that the addition of extracellular Mg(2+) (8 mM) increased the survival of cells exposed to ischaemia. As sarcolemma and mitochondria are end-effectors of cardioprotective signalling, we examined whether Mg(2+) regulates sarcolemmal and mitochondrial events. Mg(2+) (8 mM) did not affect the whole cell K(+) current as revealed by patch clamp electrophysiology. Experiments with laser confocal microscopy and the mitochondrial membrane potential-sensitive dye, JC-1, showed that Mg(2+) (8 mM) did not affect ischaemia-induced mitochondrial membrane depolarisation. However, a significantly lower JC-1 ratio was required to kill cells under control conditions than cells treated with Mg(2+) (8 mM). Based on the obtained data, we conclude that Mg(2+) protects single beating cardiomyocytes against ischaemia by increasing cellular resistance to the consequences of mitochondrial membrane depolarisation in the cytosol

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia

The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001–1 μg) was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT

Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATPSensitive Potassium Channel, Nitric Oxide, and Prostaglandins

Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others,  he mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronaryeffluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs)