Unraveling the Mechanisms of S100A8/A9 in Myocardial Injury and Dysfunction.

S100A8 and S100A9, which are prominent members of the calcium-binding protein S100 family and recognized as calprotectin, form a robust heterodimer known as S100A8/A9, crucial for the manifestation of their diverse biological effects. Currently, there is a consensus that S100A8/A9 holds promise as a biomarker for cardiovascular diseases (CVDs), exerting an influence on cardiomyocytes or the cardiovascular system through multifaceted mechanisms that contribute to myocardial injury or dysfunction. In particular, the dualistic nature of S100A8/A9, which functions as both an inflammatory mediator and an anti-inflammatory agent, has garnered significantly increasing attention. This comprehensive review explores the intricate mechanisms through which S100A8/A9 operates in cardiovascular diseases, encompassing its bidirectional regulatory role in inflammation, the initiation of mitochondrial dysfunction, the dual modulation of myocardial fibrosis progression, and apoptosis and autophagy. The objective is to provide new information on and strategies for the clinical diagnosis and treatment of cardiovascular diseases in the future.

Oxycodone attenuates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidation and pyroptosis via Nrf2/HO-1 signalling pathway.

Myocardial injury and cardiovascular dysfunction are the most common complications of sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide-induced sepsis and its related signalling pathways. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK-MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis-related proteins including: Nod-like receptor protein 3 (NLRP3), Caspase 1, Apoptosis-associated speck-like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase-1 (HO-1) because Nrf2-knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3-mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS-induced myocardial injury by suppressing NLRP3-mediated pyroptosis via the Nrf2/HO-1 signalling pathway in vivo and in vitro.

Incidence of myocardial injury in patients submitted to carotid endarterectomy.

Myocardial injury following noncardiac surgery (MINS) is associated with higher mortality and major adverse cardiovascular event rates in the short- and long-term in patients undergoing carotid endarterectomy (CEA). However, its incidence is still unclear in this subset of patients. Therefore, this systematic review with meta-analysis aims to determine the incidence of MINS in patients undergoing CEA. Three electronic databases MEDLINE, Scopus, and Web of Science were used to search for studies assessing the occurrence of MINS in the postoperative setting of patients undergoing CEA. The incidence of MINS was pooled by random-effects meta-analysis, with sources of heterogeneity being explored by meta-regression and subgroup analysis (general anesthesia vs. regional anesthesia). Assessment of studies' quality was performed using National Heart, Lung, and Blood Institute Study Quality Assessment Tool, and Risk of Bias 2 tools. Twenty studies were included, with a total of 117,933 participants. Four of them were RCTs, while the remaining were cohort studies. All observational cohorts had an overall high risk of bias, except for Pereira Macedo et al. Three of them had repeated population, thus only data from the most recent one was considered. On the other hand, all RCT had an overall low risk of bias. In patients under regional anesthesia, the incidence of MINS in primary studies ranged between 2% and 15.3%, compared to 0-42.5% for general anesthesia. The meta-analytical incidence of MINS after CEA was of 6.3% [95% CI 2.0-10.6%], but severe heterogeneity was observed (I2=99.1%). MINS appears to be relatively common among patients undergoing CEA. The observed severe heterogeneity points to the need for further larger studies adopting consistent definitions of MINS and equivalent cut-off values.

Caprylic Acid Inhibits High Mobility Group Box-1-Induced Mitochondrial Damage in Myocardial Tubes.

Myocardial damage significantly impacts the prognosis of patients with cancer; however, the mechanisms of myocardial damage induced by cancer and its treatment remain unknown. We previously reported that medium-chain fatty acids (MCFAs) improve cancer-induced myocardial damage but did not evaluate the differences in effect according to MCFA type. Therefore, this study investigated the role of inflammatory cytokines in cancer-induced myocardial damage and the effects of three types of MCFAs (caprylic acid [C8], capric acid [C10], and lauric acid [C12]). In a mouse model, the C8 diet showed a greater effect on improving myocardial damage compared with C10 and C12 diets. Myocardial tubes differentiated from H9C2 cardiomyoblasts demonstrated increased mitochondrial oxidative stress, decreased membrane potential and mitochondrial volume, and inhibited myocardial tube differentiation following treatment with high-mobility group box-1 (HMGB1) but not interleukin-6 and tumor necrosis factor-α cytokines. However, HMGB1 treatment combined with C8 improved HMGB1-induced mitochondrial damage, enhanced autophagy, and increased mitochondrial biogenesis and maturation. However, these effects were only partial when combined with beta-hydroxybutyrate, a C8 metabolite. Thus, HMGB1 may play an important role in cancer-related myocardial damage. C8 counteracts HMGB1's effects and improves cancer-related myocardial damage. Further clinical studies are required to investigate the effects of C8.

MicroRNA-330-5p Mediates the TDRG1-Regulated Myocardial Inflammation and Apoptosis after Myocardial Infarction by Inhibiting MAPK1.

Acute myocardial infarction (AMI) is a cardiovascular illness with the highest disability and mortality rates worldwide. This study aimed to estimate the mechanism of TDRG1 in myocardial damage.qRT-PCR was used to study the levels of TDRG1. After establishing hypoxia/reoxygenation (H/R) model, the inflammation was assessed by qRT-PCR, oxidation was detected by commercial kits, and apoptosis was estimated by qRT-PCR and flow cytometry. The luciferase intensity and RNA immunoprecipitation assay were detected for the identification of target relationship. The functional enrichment was unveiled by GO and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein interaction was conducted for screening key genes.The expression of TDRG1 was elevated and negatively correlated with miR-330-5p in the serum AMI patients. TDRG1/miR-330-5p axis regulated inflammation, oxidation, and viability and apoptosis of HL-1 cells induced by H/R. GO and KEGG analyses indicate that 76 overlapping targets of miR-330-5p were primarily involved in focal adhesion, calmodulin binding, and ErbB and Rap1 signaling pathways. MAPK1 was the top key gene and was a target gene of miR-330-5p.TDRG1/miR-330-5p axis could participate in the regulation of apoptosis and inflammation of H/R-induced cardiomyocytes.

Effect and mechanism of Fisetin on myocardial damage induced by Patulin.

OBJECTIVES OF THE STUDY: The aim of this study is to investigate whether fisetin can effectively reduce the myocardial damage induced by patulin. This study also aims to reveal the mechanism and target of fisetin in inhibiting myocardial damage. MATERIALS AND METHODS: Network pharmacology was used to screen the targets of fisetin on myocardial damage and the regulatory network of active ingredients-drug targets was constructed. GO and KEGG enrichment analyses were performed to screen out the key pathways and targets of fisetin on myocardial damage. Patulin induced apoptosis in H9c2 cardiomyocytes to verify the key targets. The mechanism of fisetin in inhibiting myocardial damage was determined. RESULTS: FIS can reduce the apoptosis of cardiomyocytes by protecting cardiomyocytes from PAT injury. According to the results of network pharmacology analysis, combined with enzyme activity detection and WB experiment, it was found that the mechanism of FIS to reduce myocardial damage may be related to the P53 signaling pathway, Caspase3/8/9 and Bax/Bcl-2. CONCLUSION: FIS plays a protective role in PAT-induced myocardial damage. On the one hand, FIS inhibits the protein overexpression of P53, Caspase-9 and Bax. On the other hand, FIS enhances the protein expression of Bcl-2.

Speckle-tracking echocardiography provides sensitive measurements of subtle early alterations associated with cardiac dysfunction in T2DM rats.

BACKGROUND: Diabetic cardiomyopathy results in cardiac structural and functional abnormalities. Previous studies have demonstrated that inhibiting the RhoA/ROCK signalling pathway increases the injury resistance of cardiomyocytes. The early detection of cardiac structural and functional alterations may facilitate an improved understanding of the pathophysiologic progress and guide therapy. This study aimed to identify the optimal diagnostic measures for the subtle early alterations of cardiac dysfunction in type 2 diabetes mellitus (T2DM) rats. METHODS: Twenty-four rat models were divided into four groups and received treatments for 4 weeks: the CON group (control rats), the DM group (T2DM rats), the DMF group (T2DM rats receiving fasudil) and the CONF group (control rats receiving fasudil) group. Left ventricular (LV) structure was quantified by histological staining and transmission electron microscopy. LV function and myocardial deformation were assessed by high-frequency echocardiography. RESULTS: Treatment with fasudil, a ROCK inhibitor, significantly protected against diabetes-induced myocardial hypertrophy, fibrosis and mitochondrial dysfunction. Impaired LV performance was found in T2DM rats, as evidenced by significant reductions in the ejection fraction (EF), fractional shortening (FS) and the mitral valve (MV) E/A ratio (which decreased 26%, 34% and 20%, respectively). Fasudil failed to improve the conventional ultrasonic parameters in T2DM rats, but the myocardial deformation measured by speckle-tracking echocardiography (STE) were significantly improved (global circumferential strain, GCS: P = 0.003; GCS rate, GCSR: P = 0.021). When receiver operating characteristic (ROC) curves were used in combination with linear regression analysis, STE parameters were found to be characterized by both optimal prediction of cardiac damage [AUC (95% CI): fractional area change, FAC: 0.927 (0.744, 0.993); GCS: 0.819 (0.610, 0.945); GCSR: 0.899 (0.707, 0.984)] and stronger correlations with cardiac fibrosis (FAC: r = -0.825; GCS: r = 0.772; GCSR: r = 0.829) than conventional parameters. CONCLUSION: The results suggest that STE parameters are more sensitive and specific than conventional parameters in predicting the subtle cardiac functional changes that occur in the early stage, providing new insight into the management of diabetic cardiomyopathy.

Design and synthesis of salidroside analogs and their bioactivity against septic myocardial injury.

Cardiac tissue suffers much from sepsis, and the incidence of myocardial injury is high in septic patients. The treatment of sepsis myocardial injury (SMI) has been the focus of clinical medicine. Salidroside shows myocardial cell protection, anti-oxidation and anti- inflammation effects, and it is thought as one of the potential compounds to treat sepsis myocardial injury. However, its anti-inflammatory activity is lower and its pharmacokinetic properties are not ideal, which is far from clinical application. Here, a series of salidroside analogs were synthesized, and their bioactivities were evaluated from several aspects, including their anti-oxidant and anti-inflammatory activities in vitro and anti-sepsis myocardial injury activities in vivo. Of all the compounds which synthesized, compounds 2 and 3 exhibited stronger anti-inflammatory activities than the others; after treating LPS-stimulated RAW264.7 or H9c2 cells with each of them, the levels of IL-1ß, IL-6 and TNF-α were down-regulated in a dose-dependent manner. In the anti-oxidative stress injury test, compounds 2 and 3 not only markedly increased the survival rate of cells, and but also improved the cellular oxidative stress-related indicators MDA, SOD and cell damage marker LDH in a dose-dependent manner. In the LPS-induced septic rat myocardial injury models (in vivo), the two compounds also showed good bioactivities. They also reduced the expression of IL-1ß, IL-6 and TNF-α, and blocked cell damage by suppressing overhauled oxidation in septic rats. In addition, the myocardial injury was significantly improved and the inflammatory infiltration was reduced after treatment with the two compounds. In conclusion, the salidroside analogs (2 and 3) showed promising therapeutical effect on septic myocardial injury in LPS-model rats, and they could be good candidates for clinical trials against inflammation and septic myocardial injury.

SNHG1/miR-21 axis mediates the cardioprotective role of aloin in sepsis through modulating cardiac cell viability and inflammatory responses.

BACKGROUND: Aloin has cardioprotective effects, however, its cardioprotective role in sepsis remains unclear. This study aimed to analyze whether aloin could prevent sepsis-related myocardial damage and explore the underlying mechanisms by examining the expression of long-noncoding RNA (lncRNA) SNHG1 and microRNA-21 (miR-21). METHODS: The interaction of SNHG1 with miR-21 was identified by dual-luciferase reporter assay. The levels of SNHG1 and miR-21 were measured by real-time quantitative PCR. The cardioprotective function of aloin was assessed in a sepsis animal model, which was induced by cecal ligation and puncture, and in a myocardial injury cell model in H9C2 cells stimulated by lipopolysaccharide. Myocardial injury biomarker levels and hemodynamic indicators in mice model were measured to evaluate cardiac function. The viability of H9C2 cells was assessed by cell counting kit-8 assay. Inflammatory cytokine levels were examined by an ELISA method. RESULTS: Decreased SNHG1 and increased miR-21 were found in sepsis patients with cardiac dysfunction, and they were negatively correlated. Aloin significantly attenuated myocardial damage and inflammatory responses of mice model, and increased the viability and suppressed inflammation in H9C2 cell model. In addition, SNHG1 expression was upregulated and miR-21 expression was downregulated by aloin in both mice and cell models. Moreover, in mice and cell models, SNHG1/miR-21 axis affected sepsis-related myocardial damage, and mediated the cardioprotective effects of aloin. CONCLUSION: Our findings indicated that aloin exerts protective effects in sepsis-related myocardial damage through regulating cardiac cell viability and inflammatory responses via regulating the SNHG1/miR-21 axis.

The Biological Implication of Semicarbazide-Sensitive Amine Oxidase (SSAO) Upregulation in Rat Systemic Inflammatory Response under Simulated Aerospace Environment.

The progress of space science and technology has ushered in a new era for humanity's exploration of outer space. Recent studies have indicated that the aerospace special environment including microgravity and space radiation poses a significant risk to the health of astronauts, which involves multiple pathophysiological effects on the human body as well on tissues and organs. It has been an important research topic to study the molecular mechanism of body damage and further explore countermeasures against the physiological and pathological changes caused by the space environment. In this study, we used the rat model to study the biological effects of the tissue damage and related molecular pathway under either simulated microgravity or heavy ion radiation or combined stimulation. Our study disclosed that ureaplasma-sensitive amino oxidase (SSAO) upregulation is closely related to the systematic inflammatory response (IL-6, TNF-α) in rats under a simulated aerospace environment. In particular, the space environment leads to significant changes in the level of inflammatory genes in heart tissues, thus altering the expression and activity of SSAO and causing inflammatory responses. The detailed molecular mechanisms have been further validated in the genetic engineering cell line model. Overall, this work clearly shows the biological implication of SSAO upregulation in microgravity and radiation-mediated inflammatory response, providing a scientific basis or potential target for further in-depth investigation of the pathological damage and protection strategy under a space environment.

Heart failure in a cat due to hypertrophic cardiomyopathy phenotype caused by chronic uncontrolled hyperthyroidism.

A 16-year-old castrated male Persian cat was presented with weight loss, anorexia and dyspnoea. Tachycardia and tachypnoea were observed upon presentation. The cat was previously diagnosed with hyperthyroidism and left ventricular hypertrophy and received methimazole, but was subsequently not followed up and treated appropriately. Thoracic radiography revealed mild pleural effusion, interstitial lung pattern, moderate cardiomegaly and moderate-to-severe dilation of the pulmonary artery and pulmonary vein. On echocardiography, the left ventricular hypertrophy, identified earlier, shoed partial regression. Therefore, the previous myocardial hypertrophy was diagnosed as a hypertrophic cardiomyopathy phenotype related to hyperthyroidism. ST-segment elevation was identified on electrocardiography, and the thyroid profile examination revealed increased total thyroxine and free thyroxine and decreased thyroid-stimulating hormone levels, suggesting myocardial injury and uncontrolled hyperthyroidism, respectively. In addition, normal N-terminal pro-B-type natriuretic peptide and high cardiac troponin I levels were found. Based on these findings, the observed congestive heart failure was considered as a sequel of myocardial injury caused by uncontrolled hyperthyroidism. Clinical signs resolved after intravenous administration of furosemide and butorphanol, oxygen supply and thoracocentesis. Furosemide and pimobendan were additionally administered, and the cat was discharged. This case demonstrates that myocardial damage due to chronic uncontrolled hyperthyroidism may cause heart failure in cats.

[One case of myocardial damage caused by carbamate pesticide poisoning].

The data of a patient with carbamate pesticide poisoning were analyzed. Cardiac arrest, oliguria, acute renal injury and pulmonary infection occurred during treatment. After cardiopulmonary resuscitation, tracheal intubation, CRRT, anti-infection and other symptomatic support treatment, the patient recovered and discharged. The myocardial damage caused by carbamate pesticide poisoning is easy to be ignored, and it often causes cardiac manifestations such as arrhythmia and cardiac insufficiency, and the related markers of cardiac injury, electrocardiogram and echocardiogram are also changed. Therefore, the awareness of cardiac damage caused by carbamate pesticide poisoning should be improved.

Cardiac magnetic resonance in cocaine-induced myocardial damage: cocaine, heart, and magnetic resonance.

The use of cocaine constitutes a major health problem. Cocaine use is associated with acute and chronic complications that might involve any system, the most common being the cardiovascular system. The precise incidence of cocaine-induced cardiomyopathy remains mysterious and probably underreported. Cocaine use should be considered in young patients presenting with chest pain or heart failure without other underlying risk factors. Cocaine-related cardiovascular complications can be acute or chronic and include ischemic and non-ischemic events. Frequent cocaine users have a seven-fold higher risk of myocardial infarction. In addition to its ischemic effects, other cardiovascular complications of cocaine use and abuse are hypertensive crises, aortic dissection or aortic rupture, cerebral hemorrhage, arrhythmias and sudden cardiac death, myocarditis, dilated cardiomyopathy, heart failure, and endocarditis. The mechanism of cocaine's cardiovascular toxicity relates to its sympathomimetic effect, to the block of voltage-dependent K+ and Na2+ channels, and a hypersensitivity reaction to drug or contaminants, such as amphetamine, sugars, or talc. Cardiac magnetic resonance (CMR) can provide a valuable assessment of cocaine-induced myocardial damage both in acute and chronic cardiac complications: it gives prognostic information in clinically relevant settings, and it identifies silent myocardial damage in asymptomatic patients. Indeed, CMR study should be considered in symptomatic cocaine users to assess the extent and evolution of myocardial injury. Furthermore, it was suggested to repeat CMR after 4-8 months of appropriate management to evaluate myocardial response to abstinence and medical therapy.

COVID-19 and myocarditis: a systematic review and overview of current challenges.

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19-30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further.

Downregulation of miR-34c-5p alleviates chronic intermittent hypoxia-induced myocardial damage by targeting sirtuin 1.

Numerous microRNAs (miRs) are abnormally expressed in response to hypoxia-induced myocardial damage. Herein, miR-34c-5p as a potential pharmaco-target was investigated in a mouse model of chronic intermittent hypoxia (CIH)-induced myocardial damage. A mouse model of myocardial damage was established using CIH with 7% or 21% O2 alternating 60 s for 12 h/day, 21% O2 for 12 h/day. AntagomiR-34c-5p (20 nM/0.1 ml; once a week for 12 weeks) was used as a miR-34c-5p inhibitor in a mouse model with tail-vein injection. In another experiment, mice were administrated with Sirt1 activator SRT1720 (50 mg/kg/day) by intraperitoneal injection. Gene Expression Omnibus database showed a significant upregulation of miR-34c-5p expression in the ischemic myocardium of male mice. In CIH-stimulated mice, miR-34c-5p expression was also significantly increased compared with normal mice. Treatment of antagomiR-34c-5p significantly restrained CIH-triggered myocardial apoptosis. After administration of antagomiR-34c-5p or Sirt1 activator SRT1720, cardiac hypertrophy and oxidative stress were attenuated in CIH-stimulated mice. We also found sirtuin 1 (Sirt1) as a direct target of miR-34c-5p, which was able to mediate Sirt1 protein expression in cardiomyocytes. AntagomiR-34c-5p injection markedly elevated Sirt1 protein expression in CIH-stimulated mice. AntagomiR-34c-5p or Sirt1 activator SRT1720 administration exhibited the antioxidative activity and cardioprotective roles in CIH-stimulated mice.

Exosomal circRNA as a novel potential therapeutic target for multiple myeloma-related myocardial damage.

INTRODUCTION: Myocardial damage is a mostly incurable complication of multiple myeloma (MM) that seriously affects the treatment outcome and quality of life of patients. Exosomal circular RNAs (exo-circRNAs) play an important role in tumor occurrence and development and are considered key factors in MM pathogenesis. However, the role and mechanism of action of exo-circRNAs in MM-related myocardial damage are still unclear. This study aimed to investigate correlations between exo-circRNAs and MM and to preliminarily explore the role of exo-circRNAs in MM-related myocardial damage. METHODS: Six MM patients and five healthy controls (HCs) were included in the study. High-throughput sequencing and qRT-PCR verification were used to obtain a profile of abnormally expressed exo-circRNAs. GO, KEGG, miRanda, TargetScan and Metascape were used for bioinformatics analyses. H9C2 cells treated with exosomes from U266 cells were used in cell experiments. CCK-8, PCR, immunofluorescence and western blotting assays were used to detect cell proliferation and expression of autophagy-related indicators. Electron microscopy was used to observe the number of autophagic vesicles. RESULTS: Bioinformatics analysis showed that circRNAs with upregulated expression had the potential to promote MM-related myocardial damage. In addition, PCR results confirmed that circ-G042080 was abundantly expressed in the serum exosomes of 20 MM patients. Correlation analysis showed that the expression level of circ-G042080 was positively correlated with the clinical level of MM and MM-related myocardial damage and that circ-G042080 might interfere with MM-related myocardial damage through a downstream miRNA/TLR4 axis. Cell experiments demonstrated that the circ-G042080/hsa-miR-4268/TLR4 axis might exist in H9C2 cells incubated with exosomes and cause abnormal autophagy. CONCLUSION: Abnormal expression of serum exo-circRNAs was found to be associated with MM-related myocardial damage, suggesting that exo-circRNAs might become a new diagnostic marker of MM-related myocardial damage and a therapeutic target.

In vivo analysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation.

AIMS: Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation. METHODS AND RESULTS: In six 60-75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 µL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 µL of gas, for 30 and 60 s ablation time, respectively. CONCLUSION: Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations.

Evaluation of High-Sensitivity Cardiac Troponin T Levels in Japanese Patients Recently Recovered From Coronavirus Disease 2019.

BACKGROUND: Several studies have reported elevated troponin levels in coronavirus disease 2019 (COVID-19) patients, so we investigated myocardial damage by measuring high-sensitivity troponin T (hsTnT) levels and analyzed the relationship with comorbidities.Methods and Results:Of 209 patients who recently recovered from COVID-19, 65% had an elevated hsTnT level that was higher than levels in patients with acute phase infection despite most patients (79%) having a mild illness. The hsTnT levels correlated with disease severity, sex, comorbidities, and ACEi and ARB use. CONCLUSIONS: Myocardial damage occurs in the recovery phase of COVID-19, and its evaluation, regardless of patient age, should be considered.

Rutin treats myocardial damage caused by pirarubicin via regulating miR-22-5p-regulated RAP1/ERK signaling pathway.

Our experiments have previously demonstrated that rutin (RUT) can improve myocardial damage caused by pirarubicin (THP). However, the underlying molecular mechanisms remain uncertain. In this study, we developed an microRNA (miRNA) chip by replicating the rat model of THP-induced myocardial injury and identified miR-22-5p and the RAP1-member of RAS oncogene family/extracellular regulated protein kinases (RAP1/ERK) signaling pathway as an object of study. Also, in vivo experiments demonstrated that THP caused abnormal changes in the electrocardiogram, cardiac function, and histomorphology in rats (P < .01). THP also reduces the expression of miR-22-5p (P < .01) and increases the levels of RAP1/ERK signaling pathway-related proteins (P < .01, P < .05). RUT significantly improved THP-induced myocardial damage (P < .01), increased the expression of miR-22-5p (P < .01), and decreased the levels of RAP1/ERK signaling pathway-related proteins (P < .01, P < .05). In vitro studies confirmed that Rap1a is one of the target genes of miR-22-5p. miR-22-5p overexpression in cardiomyocytes can affect the RAP1/ERK pathway and reduce reactive oxygen species production and cardiomyocyte apoptosis caused by THP (P < .01), which is consistent with the effect of RUT. Our results indicate that RUT treats THP-induced myocardial damage, which may be achieved by upregulating miR-22-5p, causing changes in its target gene Rap1a and the RAP1/ERK pathway.

Effect of Del Nido cardioplegia on ventricular arrhythmias after cardiovascular surgery.

BACKGROUND: Del Nido cardioplegia (DNC) has been proven safe and effective in pediatric patients. However, the use of DNC in adult undergoing cardiovascular surgery lacks support with substantial evidence. This study aimed to evaluate the efficacy of DNC as a cardioplegia of prophylaxis to ventricular arrhythmias associated to cardiovascular surgery in adult patients. METHODS: This study recruited nine hundred fifty-four patients who underwent cardiopulmonary bypass surgeries in Nanjing Hospital affiliated to Nanjing Medical University between January 2019 and December 2019. Among 954 patients, 324 patients were treated with DNC (DNC group), and 630 patients were treated with St. Thomas cardioplegia (STH group). The incidence of postoperative arrhythmia as well as other cardiovascular events relavant to the surgery were investigated in both groups. RESULTS: In DNC group, the incidence of postoperative ventricular arrhythmias was lower (12.4% vs. 17.4%, P = 0.040), and the length of ICU stay was shorter (1.97 ± 1.49 vs. 2.26 ± 1.46, P = 0.004). Multivariate logistic regression demonstrated that the use of DNC helped to reduce the incidence of postoperative ventricular arrhythmias (adjusted odds ratio 0.475, 95% CI 0.266-0.825, P = 0.010). The propensity score-based analysis and subgroup analysis indicated that DNC has the same protecting effects towards myocardial in all kinds of cardiopulmonary bypass surgeries. CONCLUSIONS: Del Nido cardioplegia may potentially reduce the incidence of postoperative ventricular arrhythmias, shorten the length of ICU stay and improve the overall outcome of the patients undergoing cardiovascular surgery.