FBXL19 in endothelial cells protects the heart from influenza A infection by enhancing antiviral immunity and reducing cellular senescence programs.

Influenza A virus (IAV) infection while primarily affecting the lungs, is often associated with cardiovascular complications. However, the mechanisms underlying this association are not fully understood. Here, we investigated the potential role of FBXL19, a member of the Skp1-Cullin-1-F-box family of E3 ubiquitin ligase, in IAV-induced cardiac inflammation. We demonstrated that FBXL19 overexpression in endothelial cells (ECs) reduced viral titers and IAV matrix protein 1 (M1) levels while increasing antiviral gene expression, including interferon (IFN)-α, -ß, and -γ and RANTES (regulated on activation normal T cell expressed and secreted) in the cardiac tissue of IAV-infected mice. Moreover, EC-specific overexpression of FBXL19 attenuated the IAV infection-reduced interferon regulatory factor 3 (IRF3) level without altering its mRNA level and suppressed cardiac inflammation. Furthermore, IAV infection triggered cellular senescence programs in the heart as indicated by the upregulation of p16 and p21 mRNA levels and the downregulation of lamin-B1 levels, which were partially reversed by FBXL19 overexpression in ECs. Our findings indicate that EC-specific overexpression of FBXL19 protects against IAV-induced cardiac damage by enhancing interferon-mediated antiviral signaling, reducing cardiac inflammation, and suppressing cellular senescence programs.NEW & NOTEWORTHY Our study reveals a novel facet of IAV infection, demonstrating that it can trigger cellular senescence within the heart. Intriguingly, upregulation of endothelial FBXL19 promotes host innate immunity, reduces cardiac senescence, and diminishes inflammation. These findings highlight the therapeutic potential of targeting FBXL19 to mitigate IAV-induced cardiovascular complications.

Extent of cardiac damage and hospitalization burden in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiac damage has gained increasing attention as a valid prognostic marker of mortality after transcatheter aortic valve replacement (TAVR). However, studies investigating the possible association between cardiac damage and hospitalization burden in TAVR patients are lacking. AIMS: This study aimed to investigate the impact of baseline cardiac damage on the hospitalization burden before, during, and after TAVR in an all-comers population. METHODS: All consecutive patients who underwent TAVR between 2016 and 2020 were included. Electronic medical records of all patients were examined to validate cardiovascular (CV) and heart failure (HF) related hospitalizations from 6 months before to 1 year after TAVR. Baseline cardiac damage was defined according to the staging classification by Généreux et al. RESULTS: Among 1397 TAVR patients, 94 (6.7%) had stage 0, 368 (26.4%) stage 1, 736 (52.7%) stage 2, 115 (8.2%) stage 3, and 84 (6.0%) stage 4 cardiac damage. Patients with more advanced cardiac damage at baseline had more HF hospitalizations within 6 months before TAVR (p < 0.01) and with a longer length of stay (LoS) (p < 0.01). Regarding the index TAVR admission, there was no difference in procedure time (p = 0.26) or LoS (p = 0.18) between groups. Still, TAVR patients with more advanced baseline cardiac damage had a higher risk of CV and HF rehospitalization after TAVR (p < 0.05). CONCLUSIONS: Baseline cardiac damage in patients undergoing TAVR has an impact on the pre- and post-procedural cardiovascular hospitalization burden. However, the cardiac damage status does not affect the TAVR procedure time or index TAVR admission length of stay.

The effects of berberine and curcumin on cardiac, lipid profile and fibrosis markers in cyclophosphamide-induced cardiac damage: The role of the TRPM2 channel.

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP-induced cardiac damage. Thirty-six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin-I, Creatine kinase-myocardial band (CK-MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP-ribose) polymerase-1 (PARP-1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme-linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein-1 (FSP1), transforming growth factor-beta- 1 (TGF-ß1) and α-smooth muscle actin (α-SMA) expressions were determined in heart tissue. The CYP group's troponin-I, total cholesterol, triglyceride, CK-MB, ROS, PARP-1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP-induced pathological damage, TRPM2, FSP1, TGF-ß1 and α-SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF-ß1, FSP1 and α-SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP-induced cardiac damage.

Prognostic value of extraaortic-valvular cardiac damage in patients with moderate aortic stenosis and reduced left ventricular ejection fraction.

PURPOSE: The extraaortic-valvular cardiac damage (EVCD) Stage has shown potential for risk stratification for patients with aortic stenosis (AS). This study aimed to examine the usefulness of the EVCD Stage in risk stratification of patients with moderate AS and reduced left ventricular ejection fraction (LVEF). METHODS: Clinical data from patients with moderate AS (aortic valve area, .60-.85 cm2/m2; peak aortic valve velocity, 2.0-4.0 m/s) and reduced LVEF (LVEF 20%-50%) were analyzed during 2010-2019. Patients were categorized into three groups: EVCD Stages 1 (LV damage), 2 (left atrium and/or mitral valve damage), and 3/4 (pulmonary artery vasculature and/or tricuspid valve damage or right ventricular damage). The primary endpoint included a composite of cardiac death and heart failure hospitalization, with non-cardiac death as a competing risk. RESULTS: The study included 130 patients (mean age 76.4 ± 6.8 years; 62.3% men). They were categorized into three groups: 26 (20.0%) in EVCD Stage 1, 66 (50.8%) in Stage 2, and 48 (29.2%) in Stage 3/4. The endpoint occurred in 54 (41.5%) patients during a median follow-up of 3.2 years (interquartile range, 1.4-5.1). Multivariate analysis indicated EVCD Stage 3/4 was significantly associated with the endpoint (hazard ratio 2.784; 95% confidence interval 1.197-6.476; P = .017) compared to Stage 1, while Stage 2 did not (hazard ratio 1.340; 95% confidence interval .577-3.115; P = .500). CONCLUSION: The EVCD staging system may aid in the risk stratification of patients with moderate AS and reduced LVEF.

Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene.

Patients with cancer die from cardiac dysfunction second only to the disease itself. Cardiotoxicity caused by anticancer drugs has been emphasized as a possible cause; however, the details remain unclear. To investigate this mechanism, we treated rat cardiomyoblast H9c2 cells with sunitinib, lapatinib, 5-fluorouracil, and cisplatin to examine their effects. All anticancer drugs increased ROS, lipid peroxide, and iron (II) levels in the mitochondria and decreased glutathione peroxidase-4 levels and the GSH/GSSG ratio. Against this background, mitochondrial iron (II) accumulates through the unregulated expression of haem oxygenase-1 and ferrochelatase. Anticancer-drug-induced cell death was suppressed by N-acetylcysteine, deferoxamine, and ferrostatin, indicating ferroptosis. Anticancer drug treatment impairs mitochondrial DNA and inhibits oxidative phosphorylation in H9c2 cells. Similar results were observed in the hearts of cancer-free rats treated with anticancer drugs in vitro. In contrast, treatment with pterostilbene inhibited the induction of ferroptosis and rescued the energy restriction induced by anticancer drugs both in vitro and in vivo. These findings suggest that induction of ferroptosis and inhibition of oxidative phosphorylation are mechanisms by which anticancer drugs cause myocardial damage. As pterostilbene ameliorates these mechanisms, it is expected to have significant clinical applications.

Monogenic autoinflammatory disease-associated cardiac damage.

INTRODUCTION: Autoinflammatory diseases (AIDs) constitute several disorders that are characterized by the presence of recurrent episodes of unprovoked inflammation due to dysregulated innate immune system in the absence of autoantibodies or infections. Most of them have a strong genetic background, with mutations in single genes involved in inflammation referred to monogenic AIDs. In this article, we will review the cardiac manifestations in various monogenic AIDs. AREAS COVERED: Various cardiac manifestations can be seen in various monogenic AIDs, including pericarditis, valvular diseases, coronary diseases, cardiomyopathies, and pulmonary hypertension, especially in Familial Mediterranean fever (FMF). EXPERT COMMENTARY: Monogenic AIDs can manifest a variety of cardiac lesions, the most common of which is pericardial effusion, which may be local pericardial inflammation secondary to systemic inflammatory responses. While, the pathogenesis and incidence are still unclear. More research is still needed to explore the relationship between monogenic AIDs and cardiac damage for better understanding these diseases.

The protective effect of curcumin on cardiac markers and fibrosis in abemaciclib-induced cardiac damage in rats.

Abemaciclib (ABE) is a cyclin-dependent kinase inhibitor used in combination with an antiestrogen in the treatment of breast cancer. In addition to the important therapeutic properties of this drug, its side effects are not fully known. In this study, we aimed to investigate the protective effect of curcumin (CUR) on cardiac damage caused by ABE administration. Forty rats were equally divided into control, dimethyl sulfoxide (150 µL), CUR (30 mg/kg/day), ABE (26 mg/kg/day), and ABE + CUR (26 mg/kg/day ABE and 30mg/kg/day CUR) groups (n = 8). Injections were administered daily for 28 days. Troponin-I, total cholesterol, and creatine kinase myocardial band (CK-MB) levels and cardiac fibrosis were higher in the ABE group than in the control group (p < 0.05), and were lower in the ABE + CUR group than in the ABE group (p < 0.05). The results showed that ABE administration can cause cardiac damage and increase cardiac fibrosis. However, they showed that coadministration of CUR with ABE could suppress increases in CK-MB, troponin-I, and total cholesterol levels and also cardiac fibrosis associated with cardiac damage. Therefore, we can infer that the subsequent administration of CUR ABE treatment can be used as a therapeutic strategy for preventing cardiac damage.

Astragalus (Astragalus mongholicus) Improves Ventricular Remodeling via ESR1 Downregulation RhoA/ROCK Pathway.

Astragalus (Astragalus mongholicus) alleviates myocardial remodeling caused by hypertension. However, the detailed molecular mechanism is unclear. This study aims to investigate the effect of Astragalus on ventricular remodeling in ovariectomized spontaneous hypertensive rats (OVX-SHR).Female SHR/NCrl rats were subjected to bilateral ovariectomy to establish the OVX-SHR model and treated with Astragalus extract by gavage. The hemodynamics and cardiac function parameters were measured. HE and Masson staining were used to detect the pathological structure of myocardial remodeling and observe the hyperplasia of myocardial collagen fibers. The immunohistochemistry tested the level of α-SMA. The expression levels of inflammatory cytokines, IκB, p65, Cleaved-Caspase3, RhoA, and ROCK1/2 were detected using Western blot. The method of qRT-PCR measured the expression of matrix metalloproteinase (MMP-2 and MMP-9).Hemodynamic and cardiac function parameters were significantly improved after a high dose of Astragalus extract and Valsartan treatment. The myocardial integrity of the model group was significantly reduced, arranged loosely, and disordered, while the expression of α-SMA was increased. However, Astragalus extract and Valsartan treatments significantly reduced the pathological damage and α-SMA. The levels of TNF-α, IL-1ß, IL-6, TGF-ß, MMP-2, and MMP-9 in the model group were increased but decreased after Astragalus extract treatment. Adding an ESR1 inhibitor attenuated the improvement effect of Astragalus extract on myocardial remodeling and restored the expression of RhoA and ROCK1/2.Astragalus extract attenuates the cardiac damage in OVX-SHR by downregulating the RhoA/ROCK pathway through ESR1.

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.

Validation of a novel staging classification system based on the extent of cardiac damage among Chinese patients after transcatheter aortic valve replacement: A single-center retrospective study.

OBJECTIVES: We aimed to validate a novel staging system for aortic stenosis (AS) in a Chinese patient cohort undergoing transcatheter aortic valve replacement (TAVR), and to compare this classification system to the traditional Society of Thoracic Surgeons (STS) score for TAVR risk stratification. BACKGROUND: A novel staging system for AS based on the extent of cardiac damage upon echocardiography was recently proposed. METHODS: Patients were prospectively enrolled into the Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population and analyzed retrospectively following additional exclusion criteria. On the basis of echocardiographic findings of cardiac damage, patients were classified into five stages (0-4). RESULTS: A total of 427 patients were included in the current analysis. Forty-eight deaths occurred during a median follow-up of 730 days following TAVR. The staging system showed a statistically significant association between cardiac damage and all-cause mortality; advanced stages were associated with higher mortality. In a multivariate-adjusted Cox proportional hazards regression model, stage and STS scores served as risk factors for 2-year mortality. Each increment in the staging class was associated with an increased risk of mortality (hazard ratio, 1.275; 95% confidence interval [CI], 1.052-1.545). Receiver operating characteristic (ROC) curves were plotted for stage (area under the curve, 0.644; 95% CI, 0.562-0.725) and STS score (0.661; 0.573-0.749), and with no statistically significant differences between ROC curves (p = 0.920). CONCLUSIONS: We validated a novel staging system as a key risk factor for 2-year mortality in a Chinese TAVR patient cohort. Efficacy for risk stratification was comparable to the STS score.

A simplified cardiac damage staging predicts the outcome of patients undergoing TAVR-A multicenter analysis.

BACKGROUND: A significant number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) suffer from extra-aortic cardiac damage. Few studies have investigated strategies to quantify cardiac damage and stratify patients accordingly in different risk groups. The aim of this retrospective multicenter study was to provide a user-friendly simplified staging system based on the proposed classification system of Généreux et al. as a tool to evaluate the prognosis of patients undergoing TAVR more easily. Moreover, we analyzed changes in cardiac damage after TAVR. METHODS: We assessed cardiac damage in patients, who underwent TAVR at the Heart Center Bonn or Düsseldorf, using pre- and postprocedural transthoracic echocardiography. Patients were assigned to the staging system proposed by Généreux et al. according to the severity of their baseline cardiac damage. Based on the established system, we created a simplified staging system to facilitate improved applicability. Finally, we compared clinical outcomes between the groups and evaluated changes in cardiac damage after TAVR. RESULTS: A total of 933 TAVR patients were included in the study. We found a significant association between cardiac damage and 1-year all-cause mortality (stage 0: 0% vs. stage 1: 3% vs. stage 2: 6.6%; p < 0.009). In multivariate analysis, cardiac damage was an independent predictor of 1-year all-cause mortality (hazard ratio: 2.0, 95% confidence interval: 1.1-3.8; p = 0.03). CONCLUSIONS: In patients undergoing TAVR, cardiac damage is associated with enhanced mortality. A simplified staging system can help identify patients at high risk for an adverse outcome.

Cardiovascular Damage in COVID-19: What We Know Two Years Later.

PURPOSE OF THE REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has profoundly influenced cardiological clinical and basic research in the past two years. In the present review, we summarize the current knowledge on myocardial involvement in COVID-19, providing an overview on the incidence, the pathogenetic mechanisms, and the clinical implications of cardiac injury in this setting. RECENT FINDINGS: The possibility of heart involvement in patients with COVID-19 has received great attention since the beginning of the pandemic. After more than two years, several steps have been taken in understanding the mechanisms and the incidence of cardiac injury during COVID-19 infection. Similarly, studies globally have clarified the implications of co-existing heart disease and COVID-19. Severe COVID-19 infection may be complicated by myocardial injury. To date, a direct damage from the virus has not been demonstrated. The presence of myocardial injury should be systematically assessed for a prognostication purpose and for possible therapeutic implications.

Evaluation of potential cardiotoxicity of ammonia: l-selenomethionine inhibits ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway.

Ammonia is a major harmful gas in the environment of livestock and poultry. Studies have shown that excessive ammonia inhalation has adverse effects in pig heart. However, the mechanism of ammonia-induced cardiac toxicity in pigs has not been reported. L-selenomethionine is a kind of organic selenium (Se) which is easily absorbed by the body. Therefore, in this study, twenty-four 125-day-old pigs were randomly divided into 4 groups: C (control) group, A (ammonia) group, Se group (Se content: 0.5 mg kg-1), and A (ammonia) + Se group. The mechanism of ammonia-induced cardiotoxicity and the alleviating effect of L-selenomethionine were examined. The results in the A group showed as follows: a large number of myocardial fiber edema and cytoplasmic bleakness were observed in the heart; a large number of mitochondrial autophagy were observed; ATP content, ATPase activities and hematological parameters decreased significantly; Endoplasmic reticulum stress (ERS) markers (GRP78, IRE1α, ATF4, ATF6, and CHOP) were significantly induced in the mRNA and protein levels; PI3K/AKT/mTOR signaling pathway was activated; and autophagy key genes and proteins (Beclin-1, LC3, ATG3, and ATG5) were significantly up-regulated. The results of comparison between the A + Se group and the A group were as follows: the degree of edema of cardiac muscle fiber in the A + Se group was somewhat relieved; the level of mitochondrial autophagy decreased; ATP content and ATPase activities increased significantly; the mRNA and protein levels of ERS markers were significantly down-regulated; the expression level of PI3K/AKT/mTOR signaling pathway was decreased; and the mRNA and protein levels of key autophagy genes were decreased. However, the changes of these indexes in the A + Se group were still significantly different from those in the C group. Our results indicated that L-selenomethionine supplementation inhibited ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway, which confirmed that L-selenomethionine could alleviate the cardiac injury caused by excessive ammonia inhalation to a certain extent. This study aims to enrich the toxicological mechanism of ammonia and provide valuable reference for future intervention of ammonia toxicity.

Regulation of Epicardial Cell Fate during Cardiac Development and Disease: An Overview.

The epicardium is the outermost cell layer in the vertebrate heart that originates during development from mesothelial precursors located in the proepicardium and septum transversum. The epicardial layer plays a key role during cardiogenesis since a subset of epicardial-derived cells (EPDCs) undergo an epithelial-mesenchymal transition (EMT); migrate into the myocardium; and differentiate into distinct cell types, such as coronary vascular smooth muscle cells, cardiac fibroblasts, endothelial cells, and presumably a subpopulation of cardiomyocytes, thus contributing to complete heart formation. Furthermore, the epicardium is a source of paracrine factors that support cardiac growth at the last stages of cardiogenesis. Although several lineage trace studies have provided some evidence about epicardial cell fate determination, the molecular mechanisms underlying epicardial cell heterogeneity remain not fully understood. Interestingly, seminal works during the last decade have pointed out that the adult epicardium is reactivated after heart damage, re-expressing some embryonic genes and contributing to cardiac remodeling. Therefore, the epicardium has been proposed as a potential target in the treatment of cardiovascular disease. In this review, we summarize the previous knowledge regarding the regulation of epicardial cell contribution during development and the control of epicardial reactivation in cardiac repair after damage.

Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer.

Kinase inhibitors (KIs) represent a growing class of drugs directed at various protein kinases and used in the treatment of both solid tumors and hematologic malignancies. It is a heterogeneous group of compounds that are widely applied not only in different types of tumors but also in tumors that are positive for a specific predictive factor. This review summarizes common cardiotoxic effects of KIs, including hypertension, arrhythmias with bradycardia and QTc prolongation, and cardiomyopathy that can lead to heart failure, as well as less common effects such as fluid retention, ischemic heart disease, and elevated risk of thromboembolic events. The guidelines for cardiac monitoring and management of the most common cardiotoxic effects of protein KIs are discussed. Potential signaling pathways affected by KIs and likely contributing to cardiac damage are also described. Finally, the need for further research into the molecular mechanisms underlying the cardiovascular toxicity of these drugs is indicated.

Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia.

CONTEXT: Obstructive sleep apnoea (OSA) causes chronic intermittent hypoxia (CIH), which results in mitochondrial dysfunction and generates reactive oxygen species (ROS) in the heart. Excessive free iron could accelerate oxidative damage, which may be involved in this process. Banxia-Houpu decoction (BHD) was reported to improve the apnoea hypopnoea index in OSA patients, but the specific mechanism was still unclear. OBJECTIVE: To investigate whether BHD could reduce CIH-induced heart damage by regulating iron metabolism and mitochondrial function. MATERIALS AND METHODS: C57BL/6N mice were randomly divided into control, CIH and BHD groups. Mice were exposed to CIH (21 - 5% O2, 20 times/h, 8 h/d) and administered BHD (3.51, 7.01 and 14.02 g/kg, intragastrically) for 21 d. Cardiac and mitochondrial function, iron levels, apoptosis and mitophagy were determined. RESULTS: BHD (7.01 g/kg) significantly improved cardiac dysfunction, pathological change and mitochondrial structure induced by CIH. BHD increased the Bcl-2/Bax ratio (1.4-fold) and inhibited caspase 3 cleavage in CIH mice (0.45-fold). BHD activated mitophagy by upregulating Parkin (1.94-fold) and PINK1 (1.26-fold), inhibiting the PI3K-AKT-mTOR pathway. BHD suppressed ROS generation by decreasing NOX2 (0.59-fold) and 4-HNE (0.83-fold). BHD reduced the total iron in myocardial cells (0.72-fold) and mitochondrial iron by downregulating Mfrn2 (0.81-fold) and MtFt (0.78-fold) proteins, and upregulating ABCB8 protein (1.33-fold). Rosmarinic acid, the main component of Perilla Leaf in BHD, was able to react with Fe2+ and Fe3+ in vitro. DISCUSSION AND CONCLUSIONS: These findings encourage the use of BHD to resist cardiovascular injury and provide the theoretical basis for clinical treatment in OSA patients.

[The relevance of electrocardiographic abnormalities and prognosis in patients with paraquat poisoning].

Objective: To investigate the relationship between electrocardiographic (ECG) changes and prognosis of paraquat poisoning patients, so as to provide evidence for the condition assessment in paraquat poisoning patients. Methods: In January 2022, The clinical data of paraquat poisoning patients were retrospectively analyzed in the First Affiliated Hospital of Wenzhou Medical University from January 1, 2016 to December 31, 2021. The patients' basic information (age, sex, underlying disease, and occupation) and the ECG within 24 hours were collected, and the data were statistically analyzed by SPSS 22.0. One variable analysis and multivariable logistic regression analysis were used to analyze the risk factors related to prognosis determine in their ECG. The receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of ECG indexes in patients with paraquat poisoning. Results: A total of 145 patients with paraquat poisoning were finally enrolled in this study, there were 84 patients survived and 60 patients died. One variable analysis revealed that heart rate (P=0.000) , QTc changes (P=0.000) , and ST-T changes (P=0.007) of ECG had statistically significant differences in the prognosis of paraquat poisoning patients between the survival group and the death group. Multifactorial logistic results showed that heart rate (OR=1.059, 95%CI: 1.033~1.086) and QTc (OR=1.015, 95%CI: 1.000~1.029) were independent risk factors for death diagnosis of patients with paraquat poisoning (P<0.05) . ROC curve analysis revealed that the area under the cure (AUC) of the prediction model constructed based on heart rate and QTc was 0.832 (95%CI: 0.765~0.899) , with the best diagnostic efficacy. Conclusion: Heart rate, QTc and the prediction model constructed based on both can be used as prognostic indicators for the diagnosis of patients with paraquat poisoning, and which have reference value for clinical prognosis diagnosis.

Differences in the microcirculation disturbance in the right and left ventricles of neonatal rats with hypoxic pulmonary hypertension.

Microcirculation disturbance is a crucial pathological basis of heart damage; however, microcirculation alterations induced by hypoxic pulmonary hypertension (HPH) remain unknown, and the left ventricle (LV) in HPH is conventionally ignored. Herein, we investigated the changes in the cardiac structure, function and microcirculation after HPH and further compared the differences between the right ventricle (RV) and LV. Using a neonatal rat model of HPH, we found RV myocardial hypertrophy, dysfunction and poor myocardial perfusion in HPH rats. Additionally, RV microcirculation disturbance manifested as the abnormal expression of endothelin-1/eNOS and increased expression of intercellular cell adhesion molecule-1 (ICAM-1) or E-selectin 3 days after hypoxia, followed by vascular inflammation, coronary arterial remodeling and microvascular sparseness. Impairment in LV vasodilation was detected in rats after 3 days of hypoxia; however, no obvious microvascular rarefaction or inflammatory reaction was observed in the LV. In conclusion, our results suggest that HPH mainly triggers RV microcirculation disturbances, causing low myocardial perfusion damage and cardiac dysfunction. Despite the differences in the RV and LV, their impaired microvascular function, mediated by endothelial cells, occurs almost simultaneously after HPH, earlier than cardiac functional or structural abnormalities.

Cardiac serum marker alterations after intraoperative radiotherapy with low-energy x-rays in early breast cancer as an indicator of possible cardiac toxicity.

PURPOSE: To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x­rays for early breast cancer. METHODS: We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x­rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated. RESULTS: There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N­terminal fragment of B­type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279). CONCLUSION: Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity may be therapeutically targeted by natural and chemical compounds: A review.

Doxorubicin (DOX) is a chemotherapeutic agent with marked, dose-dependent cardiotoxicity that leads to tachycardia, atrial and ventricular arrhythmia, and irreversible heart failure. Induction of the endoplasmic reticulum (ER) which plays a major role in protein folding and calcium homeostasis was reported as a key contributor to cardiac complications of DOX. This article reviews several chemical compounds that have been shown to regulate DOX-induced inflammation, apoptosis, and autophagy via inhibition of ER stress signaling pathways, such as the IRE1α/ASK1/JNK, IRE1α/JNK/Beclin-1, and CHOP pathways.