Treatment Of AMI Research Articles

Comprehensive analysis of macrophage-associated inflammatory genes in AMI based on bulk combined with single-cell sequencing data.

Previous studies have highlighted the crucial role of macrophages in the post-acute myocardial infarction (AMI) inflammatory response. This study specifically focused on investigating macrophage-related targets involved in the inflammatory response after AMI. Bioinformatics methods were applied for identifying differentially expressed genes (DEGs) in datasets GSE163465, GSE236374, and GSE183272 obtained from the Gene Expression Omnibus (GEO) database. Communication analysis was conducted to analyze macrophages in AMI. Subsequent analyses encompassed functional enrichment analysis of Co-DEGs using Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG). Gene set variation analysis (GSVA) and immune infiltration analysis were carried out for screening key genes. Validation of the bioinformatics analysis results involved original and GSE114695 datasets, supported by quantitative real time polymerase chain reaction (qRT-PCR). Animal experiments confirmed the upregulation of Saa3, Acp5, and Fcgr4 genes in AMI mouse myocardial tissues. A total of 80 and 1,907 DEGs were respectively identified by analyzing scRNA-seq and bulk RNA-seq data. The overlapping Co-DEGs were found to be closely associated with inflammation-associated pathways, specifically the PI3K-Akt-mTOR pathway. Screening based on GSVA scores and macrophage-associated scores highlighted four key genes (Saa3, Ms4a4c, Acp5, and Fcgr4). Immunoinfiltration analysis revealed their close association with macrophages. Dataset validation corroborated these findings. Experimental validation focused on Saa3, Ms4a4c, Acp5, and Fcgr4, demonstrating the upregulation of their expression in cardiac macrophages in the AMI group, consistent with previous reports. This study provides new perspectives on AMI treatment. In addition, Saa3, Acp5, and Fcgr4 exhibit potential as biomarkers for improving cardiac repair and slowing down the development of heart failure after AMI.

Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses

BackgroundSpecific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis.MethodsTo probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host’s metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota.ResultsFollowing the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI.ConclusionThis study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB’s role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.

Effect of Cold Adaptation on the State of Cardiovascular System and Cardiac Tolerance to Ischemia/Reperfusion Injury.

Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the β2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.

Results after intraoperative open and endovascular revascularization of acute mesenteric ischemia requiring a laparotomy

BackgroundAcute mesenteric ischemia (AMI) is a dreaded condition with a difficult diagnosis and high mortality. Due to different baseline situations, the frequently performed comparison between endovascular and open surgical treatment is interfered with selection bias. The purpose of this study was to review outcomes in AMI treatment with an open or endovascular approach in association with laparotomy and to evaluate the endovascular-first strategy in similar clinical situations.MethodsThe clinical data of 74 patients treated for AMI from 2007 to 2021 were retrospectively reviewed and compared. In-hospital mortality was appointed as the primary study endpoint. Risk factors for mortality were identified by using univariate and multivariate analysis.ResultsIn total, 61 patients (82%) were treated open surgically (OT) and, 13 patients (18%) with an endovascular approach (ET) in combination with laparatomy. The etiology of AMI was 49% arteriosclerotic and 51% thromboembolic occlusions. The total in-hospital mortality manifested at 43% (n =32) (OT 41% vs. ET 53.8%; P=0.54). As independent risk factors for in-hospital mortality, pneumatosis intestinalis (P=0.01), increased lactate concentration (P=0.04), and ischemic intestinal sections (P=0.01) were identified. Additionally, on univariate analysis patient age, congestive heart failure (> NYHA II) and atrial fibrillation were related with higher mortality.ConclusionsMorbidity and mortality of AMI remains at a high level. Conventional open or intraoperative endovascular therapy achieved similar results in patients with indication for laparotomy. Advanced disease stage with ischemic intestinal sections at presentation and cardiovascular comorbidities were associated with adverse outcome.

Abstract P1084: Cardiomyocyte-specific Overexpression Of Ccnd2 Via Modified Mrnafor Remuscularization In Hearts With Myocardial Infarction

Introduction: The adult mammalian heart has limited regenerative capacity due to postnatal cardiomyocyte (CM) cell cyclearrest. With the success of modified mRNA (modRNA) vaccine against SARS-CoV-2, modRNA technology offers efficient, transient, safe, nonimmunogenic, and controlled mRNA delivery without any risk of genomic integration. Using our previously reported cardiomyocyte specific modRNA translation system (CM SMRTs), we investigated the myocardial regenerative potential and therapeutic outcome of transient and specific cardiomyocyte overexpression of cyclin D2 (CCND2) in a pig model of myocardial infarction (MI). Methods: Modified mRNA was synthesized by in vitro transcription. AMI was induced by occlusion of the left anterior descending coronary artery for 60 minutes with reperfusion. Pigs were randomly assigned to vehicle group (1ml sucrose-citrate buffer, n=6), nGFP-CM SMRTs group (7.5mg CM-specific nuclear GFP modRNA, n=7)and CCND2-CM SMRTs group (7.5mg CM-specific CCND2 modRNA, n=8). CM cell cycle activity was measured 3 days after injection by immunostaining for proliferation marker Ki67, M-phase marker phospho-histone H3 (PH3) and cytokinetic marker aurora B kinase (AuB). Cardiac function was evaluated by echo and cardiac MRI (cMRI) on day 28; infarct size was determined via late gadolinium enhancement cMRI; arrhythmia incidence was assessed via implanted loop recorders. Results: The short-term in vivo study demonstrated a highly specific overexpression of targeted genes in CMs. CCND2-CM SMRTs significantly promoted CM cell cycle activation that was evidenced by significant increase of cell cycle markers compared with nGFP-CM SMRTs group: Ki67 (4.21±0.34% vs. 0.81±0.05%), PH3 (0.51±0.06% vs. 0.13±0.03%), and Symmetric AuB (0.035±0.007/mm 2 vs. 0.000±0.000/mm 2 ), 3 days after AMI and modRNA treatment. The long-term follow-up of the animals also showed improved heart function (EF: 50.34±1.94% vs. 38.60±1.18%) and decreased scar size (8.80±1.07% vs. 22.77±2.77%). The frequency of arrhythmic events in animals between all groups were similar. Conclusion: The results in large animal model of AMI demonstrate remuscularization and therapeutic potential of cardiomyocyte-specific overexpression of CCND2 via modRNA.

Amifostine attenuates bleomycin-induced pulmonary fibrosis in mice through inhibition of the PI3K/Akt/mTOR signaling pathway

Amifostine is a normal cell protection agent, not only used in the adjuvant therapy of lung cancer, ovarian cancer, breast cancer, nasopharyngeal cancer, bone tumor, digestive tract tumor, blood system tumor and other cancers in order to reduce the toxicity of chemotherapy drugs, and recent studies have reported that the drug can also reduce lung tissue damage in patients with pulmonary fibrosis, but its mechanism of action is not yet fully understood. In this study, we explored the potential therapeutic effects and molecular mechanisms of AMI on bleomycin (BLM)-induced pulmonary fibrosis in mice. A mouse model of pulmonary fibrosis was established using BLM. We then assessed histopathological changes, inflammatory factors, oxidative indicators, apoptosis, epithelial-mesenchymal transition, extracellular matrix changes, and levels of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway-related proteins in the BLM-treated mice to determine the effect of AMI treatment on these factors. BLM-treated mice had substantial lung inflammation and abnormal extracellular matrix deposition. Overall, treatment with AMI significantly improved BLM-induced lung injury and pulmonary fibrosis. More specifically, AMI alleviated BLM-induced oxidative stress, inflammation, alveolar cell apoptosis, epithelial-mesenchymal transition, and extracellular matrix deposition by regulating the PI3K/Akt/mTOR signaling pathway. This finding that AMI can alleviate pulmonary fibrosis in a mouse model by inhibiting activation of the PI3K/Akt/mTOR signaling pathway lays a foundation for potential future clinical application of this agent in patients with pulmonary fibrosis.

Managed Care after Acute Myocardial Infarction (MC-AMI) - Poland's nationwide program of comprehensive post-MI care improves prognosis in 2-year follow-up. A single high-volume center intention-to-treat analysis.

Managed Care in Acute Myocardial Infarction (MC-AMI) is a program introduced in Poland aimed at comprehensive, scheduled, and supervised care for AMI patients to improve longterm prognosis. Our study aimed to compare 24-month mortality and the incidence of major cardiovascular events (MACE: a composite of death, recurrent MI, and hospitalization for heart failure) in a cohort of AMI patients treated in the MC-AMI era (intention-to-treat analysis) vs. similar population treated before the MC-AMI era. We analyzed 2323 consecutive patients with AMI: 1261 patients enrolled in the MC-AMI era (study group) and 1062 patients treated 12 months before the MC-AMI era (control group). In the study group, 57% of patients participated in MC-AMI while 43% of patients remained under standard care. The patients were followed up for 24 months. Mortality and MACE were recorded. Treatment in the MC-AMI era was related to a 30% reduction in all-cause mortality and a 14% reduction of MACE although it was not related to the reduction of hospitalization for heart failure (HF) or AMI in 24 months. The 24-month survival rate was the highest in MC-AMI enrolled patients while patients treated in the MC-AMI era but not enrolled had a similar prognosis to those treated before the MC-AMI era. Multivariable Cox regression analysis revealed the MC-AMI era to be inversely associated with mortality in 24-month follow-up (hazard ratio [HR], 0.49; 95% confidence interval [Cl], 0.38-0.65; P <0.001). AMI treatment in the MC-AMI era reduces 24-month mortality and MACE. Moreover, AMI treatment in MC-AMI is inversely related to mortality, MACE, and hospitalization for HF. The effect is pronounced in patients enrolled in MC-AMI.

A bioinformatics approach to the identification of hub genes of Huo Xin Pill (HXP) for the treatment of acute myocardial infarction

Purpose: To apply bioinformatics for the identification of potential genes associated with Huo Xin Pill (HXP), a traditional Chinese medicine (TCM) used for the treatment of acute myocardial infarction AMI).Methods: Mouse AMI expression profile dataset GSE153485 and HXP-treated mouse AMI expression profile dataset GSE147365 were downloaded from GEO database. Then, R software was used to screen differentially-expressed genes in AMI and differentially-expressed genes in HXP-treated AMI. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, Venn diagrams, and protein-protein interaction (PPI) analysis were carried out on the hub genes linked to the effect of HXP on AMI.Results: Six hub genes were identified. Based on the differential analysis of the sham and AMI groups, GSE153485 and GSE147365 had 840 and 2116 differentially-expressed genes, respectively (p &lt; 0.05). The GO and KEGG analyses revealed enrichments in actin filament organization, membrane repolarization, and regulation of the actin cytoskeleton. Differential analysis of the use of HXP on AMI showed that GSE147365 had 380 differentially-expressed genes, comprising 96 up-regulated genes and 284 down-regulated genes (p &lt; 0.05). Thirteen potential acting target genes were obtained using a enn diagram, while 6 key acting genes were obtained via final screening.Conclusion: Six (6) hub genes linked to HXP and AMI have been identified using bioinformatics: Egr2, Tubb2a, Col4a2, Cnn2, Lmna, and Col4a1. This study provides a partial experimental basis for the use of HXP in the treatment of AMI. In addition, it provides new potential targets for the treatment of AMI.

Uncovering potential diagnostic biomarkers of acute myocardial infarction based on machine learning and analyzing its relationship with immune cells

BackgroundAcute myocardial infarction (AMI) is a common cardiovascular disease. This study aimed to mine biomarkers associated with AMI to aid in clinical diagnosis and management.MethodsAll mRNA and miRNA data were downloaded from public database. Differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were identified using the metaMA and limma packages, respectively. Functional analysis of the DEmRNAs was performed. In order to explore the relationship between miRNA and mRNA, we construct miRNA-mRNA negative regulatory network. Potential biomarkers were identified based on machine learning. Subsequently, ROC and immune correlation analysis were performed on the identified key DEmRNA biomarkers.ResultsAccording to the false discovery rate < 0.05, 92 DEmRNAs and 272 DEmiRNAs were identified. GSEA analysis found that kegg_peroxisome was up-regulated in AMI and kegg_steroid_hormone_biosynthesis was down-regulated in AMI compared to normal controls. 5 key DEmRNA biomarkers were identified based on machine learning, and classification diagnostic models were constructed. The random forests (RF) model has the highest accuracy. This indicates that RF model has high diagnostic value and may contribute to the early diagnosis of AMI. ROC analysis found that the area under curve of 5 key DEmRNA biomarkers were all greater than 0.7. Pearson correlation analysis showed that 5 key DEmRNA biomarkers were correlated with most of the differential infiltrating immune cells.ConclusionThe identification of new molecular biomarkers provides potential research directions for exploring the molecular mechanism of AMI. Furthermore, it is important to explore new diagnostic genetic biomarkers for the diagnosis and treatment of AMI.

Correlation between serum laminin levels and prognosis of acute myocardial infarction.

BackgroundAcute myocardial infarction (AMI) is a critical cardiovascular disease (CVD). Laminin (LN) is involved in the process of myocardial fibrosis and ventricular remodeling observed in AMI; however, there are currently no studies on the correlation between LN and AMI prognosis.PurposeTo explore the predictive value of serum LN levels for major adverse cardiovascular events (MACE) in patients, 6 months after an acute myocardial infarction.MethodsA total of 202 AMI patients who were hospitalized in the Department of Cardiology of the Second Affiliated Hospital of Nantong University between December 2019 and December 2020 were included. The observation endpoint was the occurrence of MACE. Univariate and multivariate logistic analyses were used to evaluate the relationships between the variables and endpoint. The predictive value of LN for MACE in AMI patients was assessed using receiver operating characteristic (ROC) analysis.ResultsA total of 47 patients developed MACE. Univariate logistic analysis showed that smoking, emergency percutaneous coronary intervention (EPCI), age, cardiac troponin I (c-TNI) levels, N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, and LN levels were associated with the occurrence of MACE (p < 0.05). Multivariate logistic analysis showed that LN was an independent predictor of MACE (odds ratio [OR] = 1.021, 95%CI: 1.014–1.032, p < 0.001). According to the ROC curve, LN can be used as an effective predictor of MACE (AUC = 0.856, 95%CI: 0.794–0.918, p < 0.001). According to the cutoff value, LN>58.80 ng/ml (sensitivity = 83.00%, specificity = 76.80%) or LN>74.15 ng/ml (sensitivity = 76.6%, specificity = 83.2%) indicate a poor prognosis for AMI. Different cut-off values are selected according to the need for higher sensitivity or specificity in clinical applications.ConclusionsLN may be a predictor of MACE following AMI in patients and could be utilized as a novel substitute marker for the prevention and treatment of AMI.

Indigenous microorganisms offset the benefits of growth and nutrition regulated by inoculated arbuscular mycorrhizal fungi for four pioneer herbs in karst soil

Arbuscular mycorrhizal (AM) fungi, as beneficial soil microorganisms, inevitably interact with indigenous microorganisms, regulating plant growth and nutrient utilization in natural habitats. However, how indigenous microorganisms affect the benefits of growth and nutrition regulated by inoculated AM fungi for plants in karst ecosystem habitats remains unclear today. In this experiment, the Gramineae species Setaria viridis vs. Arthraxon hispidus and the Compositae species Bidens pilosa vs. Bidens tripartita exist in the initial succession stage of the karst ecosystem. These plant species were planted into different soil microbial conditions, including AM fungi soil (AMF), AM fungi interacting with indigenous microorganisms soil (AMI), and a control soil without AM fungi and indigenous microorganisms (CK). The plant biomass, nitrogen (N), and phosphorus (P) were measured; the effect size of different treatments on these variables of plant biomass and N and P were simultaneously calculated to assess plant responses. The results showed that AMF treatment differently enhanced plant biomass accumulation, N, and P absorption in all species but reduced the N/P ratio. The AMI treatment also significantly increased plant biomass, N and P, except for the S. viridis seedlings. However, regarding the effect size, the AM fungi effect on plant growth and nutrition was greater than the interactive effect of AM fungi with indigenous microorganisms. It indicates that the indigenous microorganisms offset the AM benefits for the host plant. In conclusion, we suggest that the indigenous microorganisms offset the benefits of inoculated AM fungi in biomass and nutrient accumulation for pioneer plants in the karst habitat.

432 ACS-STEMI in a young man with triple positive antiphospholipid syndrome: clinical implications about antithrombotic therapy management

Abstract Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and arterial thromboembolic (TE) disease, and/or pregnancy morbidity, associated with persistent elevated antiphospholipid antibodies (lupus anticoagulant, LA, anticardiolipin, aCL, and anti-beta2-glycoprotein I, anti-β2GPI). A 51 year-old man, smoker, presented to our ER with chest pain. EKG showed Q waves and STE in the anterior leads, with increased troponin levels. A diagnosis of anterior STEMI was made and he was taken into our catheterization laboratory, where a high burden thrombotic plaque determining LM and ostial LAD subocclusion was treated with PPCI and a DES implantation; in addition, multiple failed PCI attempts were performed on a distal LAD occlusion, and an integrilin bolus was administered. The patient was admitted to our CICU and a DAPT with ASA and Ticagrelor was started. TTE showed LVEF 40%, apical akinesis, septal and anterior hypokinesis, and no significant valve disease. An aPTT abnormal value (100.5 s; reference range 25–38.5 s) was detected, not corrected by aPTT mixing study. Given suspected autoimmune prothrombotic state, normal Hb and PLT values and low bleeding risk, LMWH 100 IU/kg every 12 h was started, in addition to DAPT with switch from Ticagrelor to Clopidogrel. LA and aCL and anti-β2GPI IgG were positive, with negativity of others rheumatologic tests, confirming primary APS diagnosis. Repeat TTE showed EF 50%. The patient was discharged in ‘triple therapy’ (DAPT plus LMWH), and referred to the rheumatology clinic. LA, aCL, and anti-β2GPI tests 12 weeks later were positive, confirming a triple positive APS and satisfying revised Sapporo criteria. The rheumatologist switched therapy to Clopidogrel plus Warfarin. At 3 months follow-up, the patient, former smoker, was asymptomatic and TTE confirmed EF 50%, so he was recommended to continue with his medical therapy. APS is rarely associated with AMI (∼5.5%) and in only 2.8% cases AMI represents the onset of the disease. AMI pathogenesis in APS is considered to be acute thrombosis of coronary arteries, in contrast with atherosclerotic plaque rupture in typical AMI. Key discriminators to identify APS as potential underlying cause of AMI include young age, previous unprovoked thromboses, low platelets count (they are consumed in the thrombotic process), high aPTT value (LA may interfere with assembly of the prothrombinase complex on phospholipids), coronary artery thromboses in the setting of otherwise normal otherwise appearing coronary arteries. APS antibodies have also pro-inflammatory activity on vascular endothelial cells, leading to accelerated atherosclerosis. aGAPSS score (high risk ≥10) is useful for risk stratification of recurrent thrombosis and AMI in young patients with APS. The treatment of AMI in APS is therefore a clinical challenge. Strict management of additional CV risk factors is crucial. VKA (INR &amp;gt;3 with Warfarin, INR2–3 with Warfarin and ASA) should be provided for life, because of the very high risk of recurrent TE. DOACs are less effective and less safe than VKAs for TE prevention in APS. The role of coronary stents, considering higher rates of stent thrombosis after PCI in APS patients triple therapy concomitant risks, requires further studies. Due to lack of large, randomized, prospective studies, there is no clear experts consensus about optimal antithrombotic therapy in secondary prevention after arterial TE. APS patients with STEMI should undergo PCI, usually associated with thrombus aspiration, and in selected cases DES implantation in culprit lesion followed by triple antithrombotic therapy with short-term DAPT and long-term VKA.

592 The growth of telehealth during SARS-CoV-2 time

AimsImprove the management of frail patients, particularly in times of pandemic, through an assistance based on a remote digitalized platform, which allows rapid interventions, able to reduce access to the emergency room, and decreased mortality from cardiovascular causes. Methods and results(i) Heart failure management—Enrollment in the digital platform. Use of devices: sphygmomanometer, scale, oximeter, single-track ECG. Daily analysis of the haemodynamic parameters on the platform. Communication by e-mail exchange and tele/videoconsultations, drug management, and therapeutic strategies. Possibility to perform echocardiogram at home. (ii) Remote monitoring management—Enrollment in the digital platform. Supply of transmitters for the management of thresholds, objectives, and alarms. Daily parametric check. (iii) Infarct network management—Integrated operating system for assistance between the in-hospital and out-of-hospital environment, in patients suffering from AMI. Execution, transmission, and reporting of the ecg-graphic trace on equipment provided with a remote transmission system. Allow to reduce the time of diagnosis and treatment. At our centers, over 1000 patients are followed on a digital platform, including those at risk of heart failure and device wearers. In addition, there is an annual trend of over 400 patients who are diagnosed electronically with AMI and relative percutaneous coronary treatment. The use of remote systems has allowed for some patients to early highlight threatening arrhythmias and/or device malfunctions, for others to prematurely intercept symptoms and signs of congestive heart failure. A clear improvement in prognosis and quality of life was therefore observed.ConclusionsCardiovascular diseases are the leading cause of death in Western countries. Therefore, the close follow-up and identification of haemodynamic and clinical parameters on digitized platforms, allows to: reduce access to the emergency room, guarantee the best therapeutic strategies, improve the quality of life, and decrease the mortality rate. In conclusion, we found a high approval rating as the patient reports feeling better, feeling constantly followed, and a clear improvement in compliance and adherence to the therapy.

Current status of cardiac rehabilitation among representative hospitals treating acute myocardial infarction in South Korea.

Cardiac rehabilitation services are mostly underutilized despite the documentation of substantial morbidity and mortality benefits of cardiac rehabilitation post-acute myocardial infarction. To assess the implementation rate and barriers to cardiac rehabilitation in hospitals dealing with acute myocardial infarction in South Korea, between May and July 2016, questionnaires were emailed to cardiology directors of 93 hospitals in South Korea; all hospitals were certified institutes for coronary interventions. The questionnaires included 16 questions on the hospital type, cardiology practice, and implementation of cardiac rehabilitation. The obtained data were categorized into two groups based on the type of the hospital (secondary or tertiary) and statistically analysed. Of the 72 hospitals that responded (response rate of 77%), 39 (54%) were tertiary medical centers and 33 (46%) were secondary medical centers. All hospitals treated acute myocardial infarction patients and performed emergency percutaneous coronary intervention; 79% (57/72) of the hospitals performed coronary artery bypass grafting. However, the rate of implementation of cardiac rehabilitation was low overall (28%, 20/72 hospitals) and even lower in secondary medical centers (12%, 4/33 hospitals) than in tertiary centers (41%, 16/39 hospitals, p = 0.002). The major barriers to cardiac rehabilitation included the lack of staff (59%) and lack of space (33%). In contrast to the wide availability of acute-phase invasive treatment for AMI, the overall implementation of cardiac rehabilitation is extremely poor in South Korea. Considering the established benefits of cardiac rehabilitation in patients with acute myocardial infarction, more administrative support, such as increasing the fee for cardiac rehabilitation services by an appropriate level of health insurance coverage should be warranted.

Crowding at hospitals- the main reason for not seeking medical care when affected by an acute myocardial infarction during the first wave of COVID-19

Abstract Background Delay in seeking treatment for AMI reduces the success rate of reperfusion therapy and affects both morbidity and mortality. During the outbreak of COVID-19 pandemic, rates of hospitalization for cardiovascular diseases has decreased nationally as well as internationally and a reduction of STEMI patients with 25–48% was reported in European and US registries. The reasons for this change in health care seeking behaviour in AMI are still unknown. Purpose To evaluate possible behavioral changes in patients seeking medical care when affected by an acute myocardial infarction during the first wave on ongoing COVID-19 pandemic. Methods This was a cross sectional study in a Region in Sweden during the first wave of the COVID-19 pandemic (March-June) with patients selected from the national registry (SWEDEHEART). Eligible were patients with AMI and totally 602 patients were invited. A self-administrated psychometric evaluated queastionnaire (PA-AMI) was sent to the patientes by post and questions regarding COVID-19 were added. PA-AMI includes 14 items regarding thoughts, feelings and actions prior to care-seeking. All items are answered on a Likert-type rating scale with six grades from 1 'do not agree at all' to 6 'totally agree'. Additionally, there were questions about age, gender, country of birth, when symptoms started and when decide to seek medical care. COVID-19 questions were 'would you have sought medical care earlier if the pandemic COVID-19 would not have existed', 'if yes, why did you not seek medical care' with follow-up questions. From SWEDEHEART the following were obtained, e.g. type of AMI, history of: AMI, diabetes and percutaneous coronary intervention (PCI), date and time of first symptoms to arrival at hospital/ward or PCI lab. Results A total of 326 patients answered the questionnaire. Of these, 17% hesitated to seek medical care due to the pandemic. Patients characteristics are shown in Table 1. These patients mainly hesitated due to a fear that the healthcare was overcrowded with patients with COVID-19, followed by a fear of becoming infected by COVID-19 at the hospital (Fig 1). Women and patients not born in SWEDEN were significant more represented in this group. The self-assessed patient delay was 22 h (median) versus 4.5 h registered in SWEDEHEART. PA-AMI displayed that symptom perception and seriousness of symptoms, unsureness where to turn and difficulties to decide seek medical care, was ssociated to those who hesitated to seek medical care due to the pandemic. Conclusions During the first wave of the COVID-19 pandemic, women and patients not born in SWEDEN, as well as patients with more than one risk factor (smoking, diabetes) had a longer delay in seeking medical care for AMI due to fear of overcrowded hospitals. Therefore, these patients should be encouraged to seek medical care and there is an importance of information about how and when to seek medical care, especially in the light of COVID-19. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Blockade of the innate immune checkpoint CD47 decreases infarct size by modulation of oxidative stress and immune response

Abstract Background Myocardial infarction (MI) is the leading cause of death worldwide. Following ischemia/reperfusion (I/R) injury a precisely controlled immune response is necessary for preservation of cardiac integrity. In its course, immune cells interact with dead and damaged cells via a variety of cell surface molecules. One such interaction revolves around signal regulatory protein α (SIRPα) on myeloid cells and ubiquitously expressed CD47, which inhibits phagocytosis and was thus termed an innate immune checkpoint. Inhibition of CD47 via antibodies was shown to be protective in other I/R injury of eg liver and kidney, mostly by modulation of nitric oxide (NO) related pathways. Whether it is also beneficial in myocardial I/R injury remains to be seen. Methods and results We determined I/R injury size in murine hearts after anti-CD47 treatment using the triphenyl tetrazolium chloride (TTC)/Evans blue test and found decreased TTC negative per area at risk (AAR) at 24 h of reperfusion when compared to IgG antibody treated mice. Likewise ejection fraction was higher and plasma cardiac Troponin I (cTNI) levels were lower in anti-CD47 treated animals at the same time point. We further studied immune cell populations using flow cytometry, which revealed similar levels of neutrophils at 24 h of reperfusion in both anti-CD47 and control groups. To investigate this paradox, we deployed cutting edge light sheet fluorescence microscopy (LSFM) to simultaneously measure I/R injury size and immune cell levels and indeed found a higher ratio of neutrophils per injured area in CD47 treated mice. Furthermore, in these animals neutrophil populations were localized outside the injured area rather than only just inside, as was the case in the control group. We further measured cardiac reactive oxygen species (ROS) concentration and found ROS levels to be slightly decreased after CD47 injections following I/R. In contrast to results from other I/R injury models, we could not find an influence of anti-CD47 treatment on nitrate/nitrite/NO pathways. Conclusion Anti-CD47 treatment was shown to be protective in various I/R injury models. We could also demonstrate reduced infarct sizes after 24 h of reperfusion. This was not associated with decreased levels of neutrophils, which also located only outside of the injured area. Whether this is beneficial for the long term outcome, remains to be investigated. Nevertheless CD47 blockade presents as a highly novel and promising approach to AMI treatment and warrants further research. Funding Acknowledgement Type of funding sources: None.

A Shifting Trend Towards Endovascular Intervention in the Treatment of Acute Mesenteric Ischemia.

BackgroundAcute mesenteric ischemia (AMI) is a vascular emergency with a quite low incidence, but it is associated with disproportionately more severe morbidity and mortality. The aim of this study was to assess the current trend in the treatment of AMI and to see if endovascular intervention is an effective treatment modality in the selected group of patients.MethodsA retrospective review of patients admitted with AMI between 2007 and 2018 was performed. Outcome measures were length of stay (LOS) at hospital and intensive care unit (ICU), and post-treatment mortality.ResultsA total of 98 patients with AMI were admitted during the study period. Patients undergoing endovascular treatment compared with surgery were younger (62.9 ± 13.7 years vs. 69.5 ± 12.8 years; p = 0.01). Shorter LOS in hospital and ICU was observed for those treated with endovascular approach (6.8 ± 3.4 and 3.25 ± 0.5 days) compared to the surgical group (25 ± 8.6 and 12.8 ± 26.8 days; p < 0.001). Out of 39 patients requiring ICU admission, 48.7% were surgically treated and 10.2% underwent endovascular intervention (p < 0.001). Mortality associated with surgery was 30.6% compared to only 6.6% with endovascular intervention (p < 0.001). Between 2007 and 2012, only one patient underwent endovascular intervention and 20 underwent surgery compared to 14 patients treated with endovascular approach and 16 with surgery between 2013 and 2018.ConclusionIn this non-randomized, retrospective case series, patients with endovascular treatment fared clinically better and the intervention was found to be safe and feasible in the selected group of patients. We suggest a preference for this modality where possible. At our hospital, a trend favoring this approach is apparent during the last six years.

Application of Fluorescent Nanoparticles in Immunodetection and Emergency Treatment of Myocardial Infarction Disease

This study was to explore the feasibility of immunofluorescence based on fluorescent nanoparticles (FNP) in the detection of acute myocardial infarction (AMI) marker Cardiac troponin I (cTnI), and analyze the clinical value of optimized rescue measures in the emergency treatment of AMI. FNPs were prepared with the soap-free emulsion polymerization with potassium peroxodisulfate (KPS), styrene (St), and acrylic acid (AA) as raw materials and Nile red (NR) as fluorescent dye. FNPs were then applied to lateral flow immunoassay (LFIA). The size and Zeta potential of the FNP were measured with transmission electron microscope (TEM) and laser granulometer (LGM), respectively. The fluorescence intensity and ultraviolet (UV)-visible absorption spectrum (AP) of the FNP were detected with the fluorescence spectrophotometer (FSM) and ultraviolet spectrophotome-ter (USM), respectively. The changes in functional groups in the test sample were determined with a Fourier transform infrared spectrometer (FTIR). The sensitivity (Sen) and precision (Pre) of cTnI content detection were analyzed comprehensively. 76 AMI patients were recruited as the research objects and rolled into a control group (conventional treatment, group C) and an observation group (optimized rescue measures, group O)) with 38 cases in each group. The cTnI levels of the two groups of patients were detected before and after the treatment. In addition, the cure rates, death rates, and complications of the two groups were counted statistically. It was found that when the KPS and AA were 0.1 g and 0.4 g, the particle size was about 300 nm, the maximum wavelength of the UV-visible AP of FNP was 552 nm, and the maximum fluorescence emission wavelength was 606 nm. After the FNPs were dyed, –CH characteristic peaks were found at 1,060 cm−1 and 2,926 cm−1 in nitrogen heterocycles and aromatic heterocycles, which were similar to NR. The upper limit of cTnI concentration was 80 ng/mL, and the coefficient of variation (CV) was 1.32%–1.86%. The cTnI value of patients in group O after treatment was obviously lower than that in group C (P &lt; 0.05). The incidence of complications and death rate in the group O were considerably different from those in group C (P &lt; 0.01). To sum up, FNP was adopted in the detection of AMI marker cTnI, and the LFIA based on FNP showed high detection Sen and Pre, which can be promoted in clinical detection. In short, the optimized rescue measures improved the survival rate of AMI patients effectively.

Antidepressants fluoxetine and amitriptyline induce alterations in intestinal microbiota and gut microbiome function in rats exposed to chronic unpredictable mild stress

Antidepressant medications are known to modulate the central nervous system, and gut microbiota can play a role in depression via microbiota–gut–brain axis. But the impact of antidepressants on gut microbiota function and composition remains poorly understood. Thus this study assessed the effect of serotonin reuptake inhibitor antidepressant fluoxetine (Flu) and tricyclic antidepressant amitriptyline (Ami) administration on gut microbiota composition, diversity, and species abundance, along with microbial function in a chronic unpredictable mild stress (CUMS)-induced depression rat model. Oral administration of Ami and Flu significantly altered the overall gut microbiota profile of CUMS-induced rats, as assessed using the permutational multivariate analysis of variance test. At the phylum level, 6-week of antidepressant treatment led to a decreased Firmicutes/Bacteroidetes ratio due to an enhanced Bacteroidetes and reduced Firmicutes relative abundance. Flu was more potent than Ami at altering the Firmicutes and Bacteroidetes levels in the CUMS rats. At the family level, both antidepressants significantly increased the abundance of Porphyromonadaceae. However, an increased Bacteroidaceae level was significantly associated with Ami, not Flu treatment. Furthermore, at the genus level, an increase in the relative abundance of Parabacteroides, Butyricimonas, and Alistipes was observed following Ami and Flu treatment. Subsequent metagenomics and bioinformatics analysis further indicated that Ami and Flu likely also modulated metabolic pathways, such as those involved in carbohydrate metabolism, membrane transport, and signal transduction. Additionally, both antidepressants affected antibiotic resistome, such as for aminoglycoside (aph3iiiA), multidrug (mdtK, mdtP, mdtH, mdtG, acrA), and tetracycline (tetM) resistance in CUMS rats. These data clearly illustrated the direct impact of oral administration of Flu and Ami on the gut microbiome, thus set up the foundation to reveal more insights on the therapeutic function of the antidepressants and their overall contribution to host health.

Exploring the protective effects of PNS on acute myocardial ischaemia-induced heart failure by Transcriptome analysis

Ethnopharmacological relevancePanax notoginseng saponins (PNS) were extracted from Panax notoginseng (Burkill) F.H. Chen, a natural product often used as a therapeutic agent in China. PNS has showed obvious therapeutic effect in heart failure (HF) treatment. However, its targets and pharmacological mechanisms remain elusive. Aim of the studyThis research attempted to determine both the effects and mechanisms of PNS involved in AMI treatment, namely, acute myocardial infarction-induced HF. Materials and methodsAn AMI-induced HF model was generated by left anterior descending (LAD) ligation in rats. Transcriptome analyses were performed to identify differentially expressed genes (DEGs) and pathway enrichment. Real-time quantitative PCR (RT-qPCR) verified the HF-related genes differentially expressed after PNS treatment. Finally, a model of H9C2 cells subjected to OGD/R, which is equivalent to oxygen-glucose deprivation/reperfusion, was established to identify the potential mechanism of PNS in the treatment of HF. ResultsPNS ameliorated cardiac function and protected against structural alterations of the myocardium in HF rats. Transcriptome analysis showed that PNS upregulated 1749 genes and downregulated 1069 genes in the heart. Functional enrichment analysis demonstrated that the metabolic process was enriched among the DEGs. KEGG pathway analysis revealed that the PPAR signalling pathway was particularly involved in the protective function of PNS. The effects of PNS on the PPAR pathway were validated in vivo; PNS treatment effectively increased the expression of PPARα, RXRα, and PGC1α in rats with AMI-induced HF. In addition, PNS was shown to regulate the expression of downstream energy metabolism-related proteins. Interestingly, the addition of the PPARα inhibitor GW6471 abolished the beneficial effects of PNS. ConclusionsPNS exerts a cardioprotective function in a multicomponent and multitarget manner. The PPAR signalling pathway is one of the key pathways by which PNS protects against HF, and PPARα is a possible target for HF treatment.