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Cardiovascular diseases remain the leading cause of death in the world, and that is why finding an effective and multi-functional treatment alternative to combat these diseases has become more important. Fibrates and thiazolidinediones, peroxisome proliferator-activated receptors alpha and gamma are the pharmacological therapies used to treat dyslipidemia and type 2 diabetes, respectively. New mechanisms of action of these drugs have been found, demonstrating their pleiotropic effects, which contribute to preserving the heart by reducing or even preventing myocardial damage. Here, we review the mechanisms underlying the cardioprotective effects of PPAR agonists and regulating morphological and physiological heart alterations (metabolic flexibility, mitochondrial damage, apoptosis, structural remodeling, and inflammation). Moreover, clinical evidence regarding the cardioprotective effect of PPAR agonists is also addressed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

Abstract Aims Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625). Methods and results We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired. Conclusion In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events. Graphical Abstract Reduced myocardial contractility in low-risk patients receiving anthracycline-based cancer therapy. This study included 59 otherwise healthy women with primary breast cancer undergoing anthracycline-based chemotherapy. CMR was performed at baseline, directly and 12 months after cancer therapy. A decline in left ventricular function was observed in every single patient accompanied by transient edema. More than 50% were diagnosed with cancer therapy related cardiovascular dysfunction. LVEF: left ventricular function, CTRCD: cancer therapy related cardiovascular dysfunction, GLS = Global longitudinal strain, hs-TnT = high sensitive Troponin T, NT-pro BNP = NT-pro brain natriuretic peptide

Myocardial strain is a dimensionless parameter reflecting the degree of deformation of the whole or local myocardium under stress, which can quantitatively detect myocardial injury and guide the early diagnosis, intervention and prognostic assessment of cardiac diseases. Cardiac ultrasound, cardiac CT and cardiac magnetic resonance can all be used for strain imaging and analysis, with two-dimensional speckle-tracking echocardiography being the most widely used means of myocardial strain detection today. However, due to inter-observer variations in manual analysis of myocardial strain and differences in the imaging systems and analysis software, the consistency and reproducibility of measured strain values among vendors are poor, limiting the clinical application of myocardial strain. Artificial intelligence (AI) can overcome the defects of strain measurement to a certain extent through automatic strain calculation and image quality assessment, which has a broad developmental prospect. This review focuses on the progress of AI-assisted measurement of myocardial strain in ultrasound, magnetic resonance, and other imaging modalities, as well as its application to disease diagnosis and patient prognosis assessment. This will improve the efficiency and consistency of strain measurement and promote the routine application of myocardial strain to clinical practice, which will play an incremental role in assessing myocardial injury and cardiac function. However, most of the current studies involve small sample sizes and lack external validation, and the reliability of their results needs to be further verified.

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. [ABSTRACT FROM AUTHOR]

Introduction: Atrial septal defects (ASD) are prevalent congenital heart anomalies found in the adult population. Percutaneous ASD closure has become a routine clinical practice. Elevation of postprocedural transient cardiac biomarkers and exacerbation of supraventricular arrhythmias have been reported in the subject literature. Aim: To explore the relationship between cardiac troponin I (cTnI) elevation and supraventricular ectopy (SVE) following percutaneous closure of secundum atrial septal defect (ASD) in adult patients. Material and methods: 600 consecutive patients who underwent successful transcatheter ASD secundum closure were analyzed. Serum levels of cTnI were measured before and within 72 h of device implantation. 24-hour Holter monitoring was performed before the procedure, at 1 month, and at 6 months of follow-up. Results: SVE burden increased 1 month after the procedure (median 1021.00; min.-max. 11.00-29 862.00) compared to baseline values (median 146.00; min.-max. 0-1865.00; p < 0.01). 61.7% of patients demonstrated a cTnI rise exceeding 50% of the upper reference limit within 24 h of the procedure. A statistically significant positive correlation between SVE burden 1 month after the procedure and periprocedural cTnI increase (p < 0.05, r = 0.41) was observed, while cTnI levels significantly correlated with procedure and fluoroscopy time (p < 0.001), device size (p < 0.001) and maximal ASD diameter (p < 0.001). Conclusions: A significant increase of cTnI is noted frequently after transcatheter ASD closure and seems to predict exacerbation in SVE burden on short-term follow up. The independent risk factors of cTnI rise are prolonged procedure duration and larger device sizes. [ABSTRACT FROM AUTHOR]

Aims Aortic stenosis (AS) is causing myocardial damage and replacement is mainly indicated based on symptoms. Non-invasive estimation of myocardial work (MW) provides a less afterload-dependent too for assessing myocardial function. We sought to look at the impact of transcatheter aortic valve implantation (TAVI) on the myocardium at long-term follow-up and according to current indications. Methods and results We conducted an observational, cross-sectional, single-centre study. Patients were selected based on the validated indication for a TAVI. Standardized echocardiographies were repeated. A total of 102 patients were included. The mean age was 85 years, 45% were female, 68% had high blood pressure, and 52% had a coronary disease. One-fifth was suffering from low-flow–low-gradient AS. A follow-up was performed at 22 ± 9.5 months after the TAVI. No TAVI dysfunction was observed. Left ventricular (LV) ejection fraction was stable (62 ± 8%), and global longitudinal strain had improved (−14.0 ± 3.7 vs. −16.0 ± 3.6%, P < 0.0001). No improvement of the MW parameters was noticed (LV global work index 2099 ± 692 vs. 2066 ± 706 mmHg%, P = 0.8, LV global constructive 2463 ± 736 vs. 2463 ± 676 mmHg%, P = 0.8). Global wasted work increased [214 (149; 357) vs. 247 (177; 394) mmHg%, P = 0.0008]. Conclusion In a population of severe symptomatic AS patients who had undergone a TAVI, the non-invasive myocardial indices that assess the LV performance at long-term follow-up did not improve. These results are questioning the timing of the intervention and the need for more attention in the pharmacological management of these AS patients. [ABSTRACT FROM AUTHOR]

Background and Aim: The high concentration of myocardial damage markers against the relatively low concentration in non-cardiac tissue preserves the characteristics of the heart. The aim of this study was to investigate the effect of eightweek of exercise training in hypoxia with blood flow restriction on myocardial damage markers in active men. Materials and Methods: thirty active men from Ardabil city (mean age 38.56 ± 3.46 years and body mass index 24.45 ± 1.77 kg/ m2) were randomly selected for a study. They were divided into three groups: a hypoxia aerobic training group (A-Hypo), a resistance training with blood flow restriction group (R-BFR), and a control group (Con) with 10 participants for all groups. Two exercise groups performed selected sport exercises under special conditions for eight weeks, three times a week. One group did hypoxic training (from 25 to 40 minutes) and the other group did exercise with blood flow restriction (from 50% to 85% of maximum repetitions). Plasma cardiac intracellular troponin T (cTnT), cardiac troponin I (cTnI), homocysteine (HCY) and LDL/HDL ratio were measured using standardized methods. Analysis of covariance, Benferroni, and paired t- tests were used to analyze the results at the level of p<0.05. Results: Exercise training in the hypoxia and blood flow restriction had a significant increase in cTnI, cTnT, HCY and LDL/HDL ratio in active men (p=0.001). Conclusion: Both interventions have been shown to improve the levels of myocardial damage factors such as cTnI, cTnT and HCY, which is associated with the prevalence of myocardial damage. As a result, these interventions may have adaptive effects on the myocardium of the heart. [ABSTRACT FROM AUTHOR]

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Ischemia-reperfusion (IR) injury remains a pivotal contributor to myocardial damage following acute coronary events and revascularization procedures. Phosphoinositide 3-kinase (PI3K), a key mediator of cell survival signaling, plays a central role in regulating inflammatory responses and cell death mechanisms. Trans-chalcone (Tch), a natural compound known for its anti-inflammatory activities, has shown promise in various disease models. The aim of the current study was to investigate the potential protective effects of Tch against myocardial injury induced by ischemia and reperfusion challenges by targeting the PI3K-inflammasome interaction. Experimental models utilizing male rats subjected to an in vivo model of IR injury and myocardial infarction were employed. Administration of Tch (100 μg/kg, intraperitoneally) significantly reduced myocardial injury, as indicated by limited infarct size and decreased levels of the myocardial enzyme troponin. Mechanistically, Tch upregulated PI3K expression, thereby inhibiting the activity of the NOD-like receptor protein 3 inflammasome followed by the activation of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Moreover, it mitigated oxidative stress and suppressed vascular-intercellular adhesion molecules, contributing to its cardioprotective effects. The PI3K/Akt pathway inhibitor LY294002 considerably attenuated the beneficial effects of Tch. These findings highlight the therapeutic potential of Tch in ameliorating myocardial injury associated with IR insults through its modulation of the PI3K/Akt-inflammasome axis. The multifaceted mechanisms underlying its protective effects signify Tch as a promising candidate for further exploration in developing targeted therapies aimed at mitigating ischemic heart injury and improving clinical outcomes in cardiovascular diseases characterized by IR injury.

Abstract Objective Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). Methods We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. Results A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non‐epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. Significance The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. Plain Language Summary This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non‐epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non‐epilepsy group.

Objective To investigate the effect of moxibustion on Neiguan acupoint in preventing myocardial damage caused by anthracycline-based chemotherapy in breast cancer patients, and to explore the feasibility of moxibustion on Neiguan acupoint in reducing cardiotoxicity induced by chemotherapy. Methods A total of 80 breast cancer patients who underwent adjuvant chemotherapy with EC-T (pirarubicin + cyclophosphamide followed by docetaxel) regimen after surgery in the Department of Breast Cancer, Shaanxi Provincial Cancer Hospital from May 2020 to May 2021 were selected and divided into control group (n=40) and experimental group (n=40) randomly. During the first four cycles of chemotherapy, both groups received dexrazoxane on the same day as pirarubicin. The experimental group received moxibustion on Neiguan acupoint for three consecutive days starting one day before chemotherapy. The electrocardiograms, cardiac function, levels of cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), and Karnofsky Performance Status (KPS) score were observed before and after four cycles of chemotherapy. Results After four cycles of chemotherapy, the incidences of arrhythmia ［22.5%(9/40) vs 50.0%(20/40), χ2=6.545, P=0.011］ and QRS wave voltage decrease［27.5%(11/40) vs 55.0%(22/40), χ2=6.241, P=0.012］ in the experimental group were lower than those in the control group. The cardiac function classification in the experimental group was better than that in the control group ( Z=2.388，P＜0.017). After four cycles of chemotherapy, left ventricular ejection fraction (LVEF) decreased and left ventricular end-diastolic diameter (LVEDD) increased in the control group, while LVEF and LVEDD changes were not significant in the experimental group. The cTnI levels, NT-proBNP levels, and KPS scores increased in both groups, and LVEF, LVEDD, cTnI, NT-proBNP levels, and KPS scores were better in the experimental group than those in the control group (P＜0.05). Conclusion Moxibustion on Neiguan acupoint has a significant protective effect on myocardial damage caused by chemotherapy in breast cancer patients, and can further improve myocardial function on the basis of dexrazoxane.

Objective To investigate the effect of remimazolam on myocardial injury in rats with acute myocardial infarction (AMI) by regulating exchange proteins directly activated by cAMP (EPAC1)/RAS-related protein 1 (RAP1) signaling pathway. Methods Rats were divided into the sham operation group, the model group, the remazolam group and the remazolam+8-CPT (EPAC1 agonist) group according to random number table method, with 20 rats in each group. Except for the sham operation group, AMI rat model was constructed by ligation of left anterior descending branch in the other groups. Ultrasonic apparatus for small animals was applied to detect cardiac function indicators. HE staining was applied to detect the pathological condition of myocardial tissue. Chemical colorimetry was applied to detect levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue of rats. JC-1 staining method was applied to detect the mitochondrial membrane potential of rat cardiomyocytes. TUNEL staining was used to detect the TUNEL positive rate of myocardial cells. Western blot assay was applied to detect expression levels of EPAC1, RAP1 and Caspase-3 proteins in myocardial tissue. Results Compared with the sham operation group, the myocardial tissue structure of rats in the model group was severely damaged and infiltrated with a large number of inflammatory cells. Cardiac function indicators left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), myocardial tissue MDA level, myocardial cell TUNEL positive rate, and myocardial tissue EPAC1, RAP1 and Caspase-3 protein expression levels were obviously increased, and the left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), myocardial tissue SOD level, cardiomyocytes mitochondrial membrane potential were obviously decreased (P＜0.05). Compared with the model group, the myocardial tissue structure of rats in the ramazolam group was obviously restored, and inflammatory cell infiltration was reduced. The cardiac function indicators LVEDD, LVESD, myocardial tissue MDA level, myocardial cell TUNEL positive rate, and myocardial tissue EPAC1, RAP1 and Caspase-3 protein expression levels were obviously decreased, and LVEF, LVFS, myocardial tissue SOD level, cardiomyocytes mitochondrial membrane potential were obviously increased (P＜0.05). Agonists of EPAC1 attenuated the mitigating effect of remazolam on myocardial injury in AMI rats. Conclusion Remimazolam may inhibit the EPAC1/RAP1 signaling pathway, inhibit myocardial cell apoptosis and alleviate myocardial injury in AMI rats. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury remains a pivotal contributor to myocardial damage following acute coronary events and revascularization procedures. Phosphoinositide 3-kinase (PI3K), a key mediator of cell survival signaling, plays a central role in regulating inflammatory responses and cell death mechanisms. Trans-chalcone (Tch), a natural compound known for its anti-inflammatory activities, has shown promise in various disease models. The aim of the current study was to investigate the potential protective effects of Tch against myocardial injury induced by ischemia and reperfusion challenges by targeting the PI3K-inflammasome interaction. Experimental models utilizing male rats subjected to an in vivo model of IR injury and myocardial infarction were employed. Administration of Tch (100 μg/kg, intraperitoneally) significantly reduced myocardial injury, as indicated by limited infarct size and decreased levels of the myocardial enzyme troponin. Mechanistically, Tch upregulated PI3K expression, thereby inhibiting the activity of the NOD-like receptor protein 3 inflammasome followed by the activation of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Moreover, it mitigated oxidative stress and suppressed vascular-intercellular adhesion molecules, contributing to its cardioprotective effects. The PI3K/Akt pathway inhibitor LY294002 considerably attenuated the beneficial effects of Tch. These findings highlight the therapeutic potential of Tch in ameliorating myocardial injury associated with IR insults through its modulation of the PI3K/Akt-inflammasome axis. The multifaceted mechanisms underlying its protective effects signify Tch as a promising candidate for further exploration in developing targeted therapies aimed at mitigating ischemic heart injury and improving clinical outcomes in cardiovascular diseases characterized by IR injury. [ABSTRACT FROM AUTHOR]

Objective: Patients with epilepsy have high risk of experiencing uncommon causes of death. This study aimed to evaluate patients who underwent unusual deaths related to epilepsy and identify factors that may contribute to these deaths and may also include sudden unexpected death in epilepsy (SUDEP). Methods: We analyzed 5291 cases in which a postmortem imaging (PMI) study was performed using plane CT, because of an unexplained death. A rapid troponin T assay was performed using peripheral blood samples. Clinical information including the cause of death suspected by the attending physician, body position, place of death, medical history, and antiseizure medications was evaluated. Results: A total of 132 (2.6%) patients had an obvious history of epilepsy, while 5159 individuals had no history of epilepsy (97.4%). Cerebrovascular disease was the cause of death in 1.6% of patients in the group with epilepsy, and this was significantly lower than that in the non‐epilepsy group. However, drowning was significantly higher (9.1% vs. 4.4%). Unspecified cause of death was significantly more frequent in the epilepsy group (78.0% vs. 57.8%). Furthermore, the proportion of patients who demonstrated elevation of troponin T levels without prior cardiac disease was significantly higher in the epilepsy group (37.9% vs. 31.1%). At discovery of death, prone position was dominant (30.3%), with deaths occurring most commonly in the bedroom (49.2%). No antiseizure medication had been prescribed in 12% of cases, while 29.5% of patients were taking multiple antiseizure medications. Significance: The prevalence of epilepsy in individuals experiencing unusual death was higher than in the general population. Despite PMI studies, no definitive cause of death was identified in a significant proportion of cases. The high troponin T levels may be explained by long intervals between death and examination or by higher incidence of myocardial damage at the time of death. Plain Language Summary: This study investigated unusual deaths in epilepsy patients, analyzing 5291 postmortem imaging cases. The results showed that 132 cases (2.6%) had a clear history of epilepsy. In these cases, only 22% cases were explained after postmortem examination, which is less than in non‐epilepsy group (42.2%). Cerebrovascular disease was less common in the epilepsy group, while drowning was more common. Elevated troponin T levels, which suggest possibility of myocardial damage or long intervals between death and examination, were also more frequent in the epilepsy group compared to non‐epilepsy group. [ABSTRACT FROM AUTHOR]

Introduction: Significant attention has been paid to myocardial damage mediated by the single-stranded RNA virus. Qingfei Paidu decoction (QFPDD) has been proved to protect the damage caused by the influenza virus A/PR/8/1934 (PR8), but its specific mechanism is unclear. Methods: Molecular biological methods, together with network pharmacology, were used to analyze the effects and underlying mechanism of QFPDD treatment on PR8-induced myocardial damage to obtain insights into the treatment of COVID-19-mediated myocardial damage. Results: Increased apoptosis and subcellular damage were observed in myocardial cells of mice infected by PR8. QFPDD treatment significantly inhibited the apoptosis and subcellular damage induced by the PR8 virus. The inflammatory factors IFN-β, TNF-α, and IL-18 were statistically increased in the myocardia of the mice infected by PR8, and the increase in inflammatory factors was prevented by QFPDD treatment. Furthermore, the expression levels or phosphorylation of necroptosis-related proteins RIPK1, RIPK3, and MLKL were abnormally elevated in the group of infected mice, while QFPDD restored the levels or phosphorylation of these proteins. Our study demonstrated that HIF-1α is a key target of QFPDD in the treatment of influenza virus-mediated injury. The HIF-α level was significantly increased by PR8 infection. Both the knockdown of HIF-1α and treatment of the myocardial cell with QFPDD significantly reversed the increased inflammatory factors during infection. Overexpression of HIF-1α reversed the inhibition effects of QFPDD on cytokine expression. Meanwhile, seven compounds from QFPDD may target HIF-1α. Conclusion: QFPDD can ameliorate influenza virus-mediated myocardial damage by reducing the degree of cell necroptosis and apoptosis, inhibiting inflammatory response and the expression of HIF-1α. Thus, our results provide new insights into the treatment of respiratory virus-mediated myocardial damage. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases remain the leading cause of death in the world, and that is why finding an effective and multi-functional treatment alternative to combat these diseases has become more important. Fibrates and thiazolidinediones, peroxisome proliferator-activated receptors alpha and gamma are the pharmacological therapies used to treat dyslipidemia and type 2 diabetes, respectively. New mechanisms of action of these drugs have been found, demonstrating their pleiotropic effects, which contribute to preserving the heart by reducing or even preventing myocardial damage. Here, we review the mechanisms underlying the cardioprotective effects of PPAR agonists and regulating morphological and physiological heart alterations (metabolic flexibility, mitochondrial damage, apoptosis, structural remodeling, and inflammation). Moreover, clinical evidence regarding the cardioprotective effect of PPAR agonists is also addressed.

Objective To observe the inhibitory effects of baicalin on lipopolysaccharide(LPS)-induced pyroptosis and inflammation of cardiomyocytes and to analyze their mechanism. Methods The rat cardiomyocytes H9C2 were cultivated in vitro and we divided cells in the logarithmic growth phase into the control group, LPS group, and baicalin group. The control group did not receive intervention. In the LPS group, H9C2 cells were stimulated by LPS to construct the cell injury models in vitro. In the baicalin group, cells were induced by LPS and then were added with 10, 20, 40, and 80 µmol/L baicalin, respectively. The cell viability in each group was detected by CCK-8. The concentration of baicalin with the highest cell viability was selected as the optimal concentration for subsequent experiments. Then, H9C2 cells in the logarithmic phase were divided into the control group, LPS group, baicalin group, inhibitor group, baicalin+inhibitor group, and baicalin+activator group. Except the control group without intervention, LPS stimulation was conducted to construct the cell injury models in the other groups; on this basis, the baicalin group was treated with baicalin, while the inhibitor group was treated with phosphatidylinositol 3-kinase(PI3K)/serine protein kinase(AKT) pathway inhibitor LY294002, the baicalin+inhibitor group was treated with baicalin and LY294002, and the baicalin+activator group was treated with baicalin and PI3K/AKT pathway activator insulin-like growth factor 1(IGF-1). The inflammatory cytokines interleukin(IL)-1β and IL-6 in the cell supernatant were detected by ELISA. Western blotting was used to detect the relative expression levels of pyroptosis-related proteins pyroporin D(GSDMD), nucleotide oligomeric domain-like receptor protein 3(NLRP3), Caspase-1, and PI3K/AKT pathway-related proteins PI3K, AKT, phosphorylation(p-) PI3K, and pAKT. Results Compared with the control group, the expression levels of inflammatory cytokines IL-6, IL-1β, pyroptosis-related proteins GSDMD, NLRP3, Caspase-1, p-PI3K and p-AKT increased in the LPS group. Compared with the LPS group, the expression levels of IL-6, IL-1β, GSDMD, NLRP3, Caspase-1, p-PI3K and p-AKT decreased in the baicalin group and inhibitor group. Compared with the baicalin group, the expression levels of IL-6, IL-1β, GSDMD, NLRP3, Caspase-1, p-PI3K and p-AKT decreased in the baicalin + inhibitor group, while the trend was opposite in the baicalin + activator group(all P<0. 05). Conclusion Baicalin could inhibit the inflammatory response and pyroptosis of rat cardiomyocytes in vitro induced by LPS, and the mechanism may be related to inhibiting the activation of PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) is not used routinely as a diagnostic biomarker in newborns. The high precision of hs-cTnT assays increases the ability to determine small differences in cTnT over time and to detect troponin T elevation; thus, we believe that hs-cTnT assays might improve clinical care. We explored the plausible association between hs-cTnT levels (ng/L) in healthy newborns and prolonged second stage of labor, neonatal, and maternal factors. Methods: A prospective study was performed among healthy newborns in the Obstetrics and Gynecology Department at Hillel Yaffe Medical Center in Israel in January–June 2021. The sociodemographic characteristics of the participants, maternal age, gravidity, parity, Pitocin use, epidural analgesia, and neonatal anemia were obtained from the electronic medical records. Gestational age was determined by ultrasound biometric measurements. We classified second-stage labor as normal or prolonged using the WHO guidelines. Samples from umbilical cord blood were drawn using syringes rinsed with anticoagulant by a specialist in pediatrics. The remaining blood was used to determine hs-cTnT levels (ng/L), which was defined as a continuous quantitative variable with the median value and the 25th–75th percentiles. Results: Overall, 184 cord blood samples were performed from healthy newborns (60.6% males) with a median hs-cTnT of 39.03 (25th–75th percentiles = 30.53–54.09) ng/L. A multivariable linear regression model showed no significant association between neonatal anemia and hs-cTnT levels (ng/L) (p = 0.8). Gestational age (B coefficient −4.24, p < 0.001) and gravidity (B coefficient −2.41, p = 0.03) were negatively associated with hs-cTnT levels (ng/L), while Pitocin use (B coefficient 6.91, p = 0.04) and prolonged second stage of labor (B coefficient 18.07, p = 0.02) were positively associated with hs-cTnT levels (ng/L). Conclusions: High hs-cTnT levels (ng/L) were documented in the cord blood of healthy newborns. Hs-cTnT levels were positively correlated with a prolonged second stage of labor and Pitocin use and negatively correlated with longer gestational age and higher gravidity. Hs-cTnT may signify labor-related fetal distress. A larger surveillance study is mandatory to establish this correlation and assess for possible prognostic significance of elevated hs-cTnT in this context. [ABSTRACT FROM AUTHOR]

To study the effect of restrictive fluid resuscitation on coagulation function, myocardial damage indicators, and prognosis in patients with multiple fractures combined with traumatic hemorrhagic shock. 90 in patients with multiple fractures combined with traumatic hemorrhagic shock who received treatment in our hospital from June 2020 to May 2022 were selected for this study, according to random number table method, they were divided into study group (n=47) and control group (n=43), the control group received routine liquid resuscitation treatment, on the basis of the control group, the research group used restrictive fluid resuscitation therapy. Compare the infusion volume, blood loss, transfusion volume, coagulation function indicators (PT, APTT, TT) levels before and 1 hour after resuscitation, myocardial damage indicators (CK, CK-MB, CTnT) levels, and incidence of complications between the two groups. The infusion volume, blood loss, and transfusion volume of the research group were significantly lower than those of the control group [(2106.87± 135.62) mL vs (2950.39± 139.57) mL, (1049.31± 160.07) mL vs (1390.18 ± 135.89) mL, (1465.02± 191.78) mL vs(1860.23± 198.59)mL] (P＜0.05). The levels of PT, APTT, and TT in the study group were significantly higher than those in the control group [(19.06± 1.80) s vs (15.82± 1.26) s, (42.03± 3.85) s vs (37.02± 3.19) s, (21.03± 3.86) s vs (15.80± 3.27) s] (P＜ 0.05). The levels of CK, CK-MB, and CTnT in the study group were significantly lower than those in the control group [(20.85± 2.72) U/L vs (32.97± 3.69)U/L, (23.06± 3.28)U/L vs (35.97± 3.70)U/L, (2.07± 0.36) ng/mL vs (2.90± 0.38) ng/mL] (P＜0.05). The incidence of complications in the study group was significantly lower than that in the control group [10.64%(5/47) vs 27.91％(12/43)] (P＜ 0.05). Restrictive fluid resuscitation can effectively improve the coagulation function, protect myocardial cells and improve the prognosis of patients with multiple fractures and traumatic hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Objective To explore the diagnostic value of ECG changes in children with mycoplasma pneumonia complicated by myocardial damage. Methods A total of 296 children with mycoplasma pneumonia were selected. According to the absence or presence of ECG abnomalities, they were divided into normal ECG group (82 cases) and abnormal ECG group (214 cases). One hundred health children were selected as control group. Basic conditions and difference of myocardial damage were comparatively analyzed among the three groups. The correlation between ECG abnormalities and myocardial damage, and the proportion of each type of ECG abnormalities were also analyzed. Results There is no significant difference in age or sex ratio among groups (P> 0. 05). The myocardial enzyme indexes in the abnormal ECG group are significantly higher than those of the normal ECG group and the control group. Only each myocardial enzyme index of the control group is within the normal reference range. And the difference of each index is statistically significant among the three groups (P < 0. 01). Among the children with mycoplasma pneumonia, ECG abnormalities are significantly correlated with myocardial damage (χ² = 8. 248,P<0. 05), that is, the probability of complicated myocardial damage significantly increases in child patients with ECG abnormalities. In the child patients with mycoplasma pneumonia, various types of ECG abnormalities are found, including arrhythmias and ST-T changes, among which sinus tachycardia, ST-T changes and sinus arrhythmia are more common, accounting for 44. 86%, 34. 11% and 12. 15%, respectively. Conclusion ECG abnormalities have important diagnostic value in child patients with mycoplasma pneumonia complicated by myocardial damage, which help to make early diagnosis and treatment, and improve the prognosis. [ABSTRACT FROM AUTHOR]

• CB2 receptors activation alleviates myocardial inflammation and damage in mice with sepsis. • Pyroptosis is inhibited during CB2 receptors activation in myocardium of septic mice. • Pyroptosis is an important signal pathway in the anti-inflammatory effect of CB2 receptors. It has been reported that cannabinoid receptors 2 (CB2 receptors) play an important role in the pathophysiological process of sepsis, which may also be associated with the regulation of pyroptosis, an inflammatory programmed cell death. The present study aimed to investigate the protective effect of CB2 receptors on myocardial damage in a model of septic mice by inhibiting pyroptosis. The C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce sepsis. All mice were randomly divided into the sham, CLP, or CLP+HU308 group. Blood and heart tissue samples were collected 12 h after surgery. Hematoxylin and eosin staining was used for analyzing histopathological results. Creatine kinase isoenzymes (CK-MB) and IL-1β were measured using ELISA, while lactate dehydrogenase (LDH) level was determined using photoelectric colorimetry. The expression levels of CB2 receptors and pyroptosis-associated proteins (NLRP3, caspase-1, and GSDMD) were measured using western blotting. The location and distribution of CB2 receptors and caspase-1 in myocardial tissues were assessed by immunofluorescence. TUNEL staining was used to quantify the number of dead cells in myocardial tissues. The CLP procedure increased CB2 receptor expression in mice. CB2 receptors were located in myocardial macrophages. Activating CB2 receptors decreased the levels of myocardial damage mediator LDH, CK-MB, and inflammatory cytokine IL-1β. The results also showed that CLP increased the pyroptosis in myocardial tissues, while CB2 agonist HU308 inhibited pyroptosis by decreasing the level of NLRP3 and activating caspase-1 and GSDMD. CB2 receptor activation has a protective effect on the myocardium of mice with sepsis by inhibiting pyroptosis. [ABSTRACT FROM AUTHOR]

Heart failure is a continuously developing syndrome of cardiac insufficiency caused by diseases, which becomes a major disease endangering human health as well as one of the main causes of death in patients with cardiovascular diseases. The occurrence of heart failure is related to hemodynamic abnormalities, neuroendocrine hormones, myocardial damage, myocardial remodeling etc, lead to the clinical manifestations including dyspnea, fatigue and fluid retention with complex pathophysiological mechanisms. Currently available drugs such as cardiac glycoside, diuretic, angiotensin-converting enzyme inhibitor, vasodilator and β receptor blocker etc are widely used for the treatment of heart failure. In particular, natural products and related active ingredients have the characteristics of mild efficacy, low toxicity, multi-target comprehensive efficacy, and have obvious advantages in restoring cardiac function, reducing energy disorder and improving quality of life. In this review, we mainly focus on the recent advance including mechanisms and active ingredients of natural products for the treatment of heart failure, which will provide the inspiration for the development of more potent clinical drugs against heart failure.

We aimed to investigate the potential benefits of two doses of ivabradine (IVA)-an If sodium channel blocker against isoproterenol (ISO)-induced myocardial damage in rats.The rats were randomly divided into 4 groups: Control group (n=8); Saline was administered, ISO group (n=12); 150 mg/kg ISO was administered for 2 days, ISO+IVA (1 mg/kg) group (n=12); 1 mg/kg IVA was administered for 4 days in addition to ISO. ISO+IVA (10 mg/kg) group (n=12): 10 mg/kg IVA was administered for 4 days in addition to ISO. Thereafter, hemodynamic, histopathological, and biochemical studies were performed. In the ISO+IVA (1 mg/kg) and ISO+IVA (10 mg/kg) groups, ISO-induced myocardial changes including an increase in density of granulation tissue and degenerated cardiomyocyte were equally decreased. HR was mildly reduced, and arterial blood pressures were slightly increased in the IVA-treated groups versus the ISO group. In the hearts of IVA-treated groups, malondialdehyde (MDA) levels were significantly reduced and glutathione (GSH) level and catalase (CAT) activity were mildly increased compared to the ISO group. Elevation of GSH and CAT activity were more pronounced in the ISO+IVA (10 mg/kg) group. Our results indicate that both 1 mg/kg and 10 mg/kg doses of IVA are effective against heart damage induced by ISO via its negative chronotropic, anti-oxidant (dose-dependent), anti-inflammatory and anti-degenerative properties. [Med-Science 2023; 12(3.000): 667-73]

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.

Antioxidant protection is one of the key reactions of cardiomyocytes (CMCs) in response to myocardial damage of various origins. The thioredoxin interacting protein (TXNIP) is an inhibitor of thioredoxin (TXN). Over the recent few years, TXNIP has received significant attention due to its wide range of functions in energy metabolism. In the present work, we studied the features of the redox-thiol systems, in particular, the amount of TXNIP and glutathione synthetase (GS) as markers of oxidative damage to CMCs and antioxidant protection, respectively. This study was carried out on 38-week-old Wistar-Kyoto rats with insulin-dependent diabetes mellitus (DM) induced by streptozotocin, on 38- and 57-week-old hypertensive SHR rats and on a model of combined hypertension and DM (38-week-old SHR rats with DM). It was found that the amount of TXNIP increased in 57-week-old SHR rats, in diabetic rats and in SHR rats with DM. In 38-week-old SHR rats, the expression of TXNIP significantly decreased. The expression of GS was significantly higher compared with the controls in 57-week-old SHR rats, in DM rats and in the case of the combination of hypertension and DM. The obtained data show that myocardial damage caused by DM and hypertension are accompanied by the activation of oxidative stress and antioxidant protection.

Myocardial damage is the most serious pathological consequence of cardiovascular diseases and an important reason for their high mortality. In recent years, because of the high prevalence of systemic energy metabolism disorders (e.g., obesity, diabetes mellitus, and metabolic syndrome), complications of myocardial damage caused by these disorders have attracted widespread attention. Energy metabolism disorders are independent of traditional injury-related risk factors, such as ischemia, hypoxia, trauma, and infection. An imbalance of myocardial metabolic flexibility and myocardial energy depletion are usually the initial changes of myocardial injury caused by energy metabolism disorders, and abnormal morphology and functional destruction of the mitochondria are their important features. Specifically, mitochondria are the centers of energy metabolism, and recent evidence has shown that decreased mitochondrial function, caused by an imbalance in mitochondrial quality control, may play a key role in myocardial injury caused by energy metabolism disorders. Under chronic energy stress, mitochondria undergo pathological fission, while mitophagy, mitochondrial fusion, and biogenesis are inhibited, and mitochondrial protein balance and transfer are disturbed, resulting in the accumulation of nonfunctional and damaged mitochondria. Consequently, damaged mitochondria lead to myocardial energy depletion and the accumulation of large amounts of reactive oxygen species, further aggravating the imbalance in mitochondrial quality control and forming a vicious cycle. In addition, impaired mitochondria coordinate calcium homeostasis imbalance, and epigenetic alterations participate in the pathogenesis of myocardial damage. These pathological changes induce rapid progression of myocardial damage, eventually leading to heart failure or sudden cardiac death. To intervene more specifically in the myocardial damage caused by metabolic disorders, we need to understand the specific role of mitochondria in this context in detail. Accordingly, promising therapeutic strategies have been proposed. We also summarize the existing therapeutic strategies to provide a reference for clinical treatment and developing new therapies. [Display omitted] Myocardial damage caused by energy metabolism disorders has become a serious threat to human health. Abnormal mitochondrial behaviors play a key role in myocardial damage caused by energy metabolism disorders. Mitochondrial transfer can rescue myocardial injury and has strong therapeutic potential. Disruption of redox homeostasis affects mitochondrial behaviors and exacerbates myocardial injury. Sirtuins and coupling between mitochondrial behaviors are interesting research directions. [ABSTRACT FROM AUTHOR]

Pneumonia is a common clinical disease in the neonatal period and poses a serious risk to infant health. Therefore, the understanding of molecular mechanisms is of great importance for the development of methods for the rapid and accurate identification, classification and staging, and even disease diagnosis and therapy of pneumonia. In this study, a nontargeted metabonomic method was developed and applied for the analysis of serum samples collected from 20 cases in the pneumonia control group (PN) and 20 and 10 cases of pneumonia patients with metabolic acidosis (MA) and myocardial damage (MD), respectively, with the help of ultrahigh-performance liquid chromatography–high-resolution mass spectrometry (UPLC–HRMS). The results showed that compared with the pneumonia group, 23 and 21 differential metabolites were identified in pneumonia with two complications. They showed high sensitivity and specificity, with the area under the curve (ROC) of the receiver operating characteristic curve (ROC) larger than 0.7 for each differential molecule. There were 14 metabolites and three metabolic pathways of sphingolipid metabolism, porphyrin and chlorophyll metabolism, and glycerophospholipid metabolism existing in both groups of PN and MA, and PN and MD, all involving significant changes in pathways closely related to amino acid metabolism disorders, abnormal cell apoptosis, and inflammatory responses. These findings of molecular mechanisms should help a lot to fully understand and even treat the complications of pneumonia in infants. [ABSTRACT FROM AUTHOR]

Anomalous origin of right coronary artery (RCA) from pulmonary artery (ARCAPA) with atrial septal defect (ASD) and patent ductus arteriosus (PDA) is a rare presentation. Anatomic abnormalities of coronary arteries may be subtle, and echocardiographic evaluation is difficult in many cases especially in absence of significant myocardial damage. We report a case of a four years old boy who was admitted for ostium secondum ASD closure and was incidentally detected to have ARCAPA intra-operatively. The right coronary artery was re-implanted to the aorta with closure of ASD and PDA ligation. The association of ARCAPA with ostium secondum ASD and PDA is relatively rare. The presence of left to right shunt affects the pathophysiology of ARCAPA and makes the preoperative diagnosis difficult. Surgical correction is mandatory to prevent further myocardial dysfunction. [ABSTRACT FROM AUTHOR]

We aimed to investigate the potential benefits of two doses of ivabradine (IVA)-an If sodium channel blocker against isoproterenol (ISO)-induced myocardial damage in rats. The rats were randomly divided into 4 groups: Control group (n=8); Saline was administered, ISO group (n=12); 150 mg/kg ISO was administered for 2 days, ISO+IVA (1 mg/kg) group (n=12); 1 mg/kg IVA was administered for 4 days in addition to ISO. ISO+IVA (10 mg/kg) group (n=12): 10 mg/kg IVA was administered for 4 days in addition to ISO. Thereafter, hemodynamic, histopathological, and biochemical studies were performed. In the ISO+IVA (1 mg/kg) and ISO+IVA (10 mg/kg) groups, ISO-induced myocardial changes including an increase in density of granulation tissue and degenerated cardiomyocyte were equally decreased. HR was mildly reduced, and arterial blood pressures were slightly increased in the IVA-treated groups versus the ISO group. In the hearts of IVA-treated groups, malondialdehyde (MDA) levels were significantly reduced and glutathione (GSH) level and catalase (CAT) activity were mildly increased compared to the ISO group. Elevation of GSH and CAT activity were more pronounced in the ISO+IVA (10 mg/kg) group. Our results indicate that both 1 mg/kg and 10 mg/kg doses of IVA are effective against heart damage induced by ISO via its negative chronotropic, anti-oxidant (dose-dependent), anti-inflammatory and anti-degenerative properties. [ABSTRACT FROM AUTHOR]

Abstract 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.

IntroductionExtracorporeal cardiopulmonary resuscitation (ECPR) is an emerging strategy in highly selected patients with refractory cardiac arrest (CA). Animal models can help to identify new therapeutic strategies to improve neurological outcome and cardiac function after global ischemia in CA. Aim of the study was to establish a reproducible ECPR rat model of ventricular fibrillation CA (VFCA) that leads to consistent neuronal damage with acceptable long-term survival rates, which can be used for future research.Materials and methodsMale Sprague Dawley rats were resuscitated with ECPR from 6 min (n = 15) and 8 min (n = 16) VFCA. Animals surviving for 14 days after return of spontaneous resuscitation (ROSC) were compared with sham operated animals (n = 10); neurological outcome was assessed daily until day 14. In the hippocampal cornu ammonis 1 region viable neurons were counted. Microglia and astrocyte reaction was assessed by Iba1 and GFAP immunohistochemistry, and collagen fibers in the myocardium were detected in Azan staining. QuPath was applied for quantification.ResultsOf the 15 rats included in the 6 min CA group, all achieved ROSC (100%) and 10 (67%) survived to 14 days; in the 8 min CA group, 15 (94%) achieved ROSC and 5 (31%) reached the endpoint. All sham animals (n = 10) survived 2 weeks. The quantity of viable neurons was significantly decreased, while the area displaying Iba1 and GFAP positive pixels was significantly increased in the hippocampus across both groups that experienced CA. Interestingly, there was no difference between the two CA groups regarding these changes. The myocardium in the 8 min CA group exhibited significantly more collagen fibers compared to the sham animals, without differences between 6- and 8-min CA groups. However, this significant increase was not observed in the 6 min CA group.ConclusionOur findings indicate a uniform occurrence of neuronal damage in the hippocampus across both CA groups. However, there was a decrease in survival following an 8-min CA. Consequently, a 6-min duration of CA resulted in predictable neurological damage without significant cardiac damage and ensured adequate survival rates up to 14 days. This appears to offer a reliable model for investigating neuroprotective therapies.

Non-alcoholic fatty liver disease (NAFLD) can lead to myocardial damage and is a risk factor for cardiac insufficiency. Myocardial strain (MS) detection is a new technique that has been rapidly developed in recent years and has become a common tool for quantifying myocardial deformation and diagnosing and predicting subclinical myocardial injury. MS can not only accurately assess local and global myocardial injury, but also detect changes of cardiac function in NAFLD patients with normal ejection fraction. Understanding myocardial injury caused by NAFLD, timely detection, diagnosis and prediction of cardiac dysfunction in patients with NAFLD by MS detection technique are of great clinical significance in preventing the progression of irreversible heart failure. This article reviews the pathophysiological mechanisms of myocardial injury caused by NAFLD, MS detection techniques and the use of MS detection techniques in atria and ventricle in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Aging process is associated with higher inflammatory and cardiovascular risk factors. Remote ischemic preconditioning and high-intensity interval training have been known as useful strategies for health problem prevention and management. The aim of this study was to investigate the influence of remote ischemic preconditioning and high-intensity interval training on cardiac troponin I, creatine kinase-MB, IL10, and C-reactive protein in middle-aged male Wistar rats. Twenty-four male Wistar rats (12-month-old) were randomly assigned to four groups: high-intensity interval training (HIIT), remote ischemic preconditioning + high-intensity interval training (RIPC + HIIT), sham-high-intensity interval training (Sham HIIT), and sham-remote ischemic preconditioning + high-intensity interval training (Sham RIPC + HIIT). The rats in the experimental groups were administered to the selected protocols of 3 days a week for 21 days. Then, animals were sacrificed 48 h following the last session, and blood samples were collected and analyzed with ELISA method for the cardiac troponin I, creatine kinase-MB, IL10, and C-reactive protein. Both of the selected protocols led to a significant decrease in CKMB and IL10; however, the cTnI elevated meaningfully in RIPC + HIIT compared to the sham groups, and CRP was not significantly different between the groups (P < 0.05). This study demonstrated that 3 weeks of HIIT did not significantly alter cTnI and CRP and caused a reduction in CK-MB as a myocardial injury biomarkers in middle-aged male Wistar rats. On the other hand, applying RIPC caused a significant elevation in cTnI. Therefore, these physiological adaptations can improve ischemic tolerance and inhibit myocardial infarction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Antioxidant protection is one of the key reactions of cardiomyocytes (CMCs) in response to myocardial damage of various origins. The thioredoxin interacting protein (TXNIP) is an inhibitor of thioredoxin (TXN). Over the recent few years, TXNIP has received significant attention due to its wide range of functions in energy metabolism. In the present work, we studied the features of the redox-thiol systems, in particular, the amount of TXNIP and glutathione synthetase (GS) as markers of oxidative damage to CMCs and antioxidant protection, respectively. This study was carried out on 38-week-old Wistar-Kyoto rats with insulin-dependent diabetes mellitus (DM) induced by streptozotocin, on 38- and 57-week-old hypertensive SHR rats and on a model of combined hypertension and DM (38-week-old SHR rats with DM). It was found that the amount of TXNIP increased in 57-week-old SHR rats, in diabetic rats and in SHR rats with DM. In 38-week-old SHR rats, the expression of TXNIP significantly decreased. The expression of GS was significantly higher compared with the controls in 57-week-old SHR rats, in DM rats and in the case of the combination of hypertension and DM. The obtained data show that myocardial damage caused by DM and hypertension are accompanied by the activation of oxidative stress and antioxidant protection. [ABSTRACT FROM AUTHOR]

For today the exact mechanisms of myocardial infarction and ischemia/reperfusion injury are still not fully understood. ER stress and integrated stress response pathways are thought to play an essential role in myocardial damage. This includes activation of endoplasmic reticulum kinase (PERK), induction of activating transcription factor 4 (ATF4), expression of pro-apoptotic transcription factor (CHOP) and P53 up-regulated modulator of apoptosis (PUMA) involved in apoptosis control. We used a rat model of isoproterenol-induced myocardial damage to elucidate the possible cardioprotective effect of Ginger through the influence on ER stress-induced apoptotic pathway. We also compared its effect with Captopril, inhibitor of angiotensin-converting enzyme. Male albino Wistar rats received 1.0 or 2.0 ml of Zingiber officinale (Ginger) powder suspension (200 mg/ml) daily by intra-gastric intubation for 28 days. Isoproterenol at a dose of 85 mg/kg was IP injected on the 27th and 28th days. Serum aspartate transaminase (AST) level was measured using kinetic kit. Heart tissue was used for RNA extraction, evaluation of gene expression by Q-RT-PCR, immuno-histochemical determination of caspase-3 expression and histopathological studies. Our results showed that Isoproterenol administration increased CHOP-mRNA expression 4 folds in cardiac muscle tissue compared to normal control. Ginger pretreatment significantly decreased both CHOP and ATF4, and PUMA mRNA expression compared to Isoproterenol-treated groups. A significant reduction in ATF4 mRNA expression in a group pretreated with Captopril and Ginger compared to normal control group was observed. The results showed that Ginger reduced AST serum levels which correlated with results of histopathological studies of heart tissue. Our findings suggest that the protective effects of Ginger against myocardium damage induced by Isoproterenol may be mediated by reducing­ the endoplasmic reticulum stress by affecting the ATF4-CHOP-PUMA pathway.

Cardiorenal interaction in acute heart failure (AHF) is becoming an increasingly recognized factor to consider in the management of cardiac surgical patients. Achieving adequate control of water balance and simultaneously preserving kidney function is the goal of the optimal management strategy for patients with AHF. The majority of preoperative hospitalizations to intensive care units in patients with infective endocarditis (IE) are associated with the development of AHF. The term “cardiorenal syndrome” (CRS) is used to define kidney dysfunction on the background of AHF. Due to the lack of clear clinical manifestations of CRS in IE, the diagnosis and treatment of this pathology may be delayed and contribute to the increase in the number of postoperative complications. Recent data, both in basic science and in clinical research, have changed our understanding of CRS. To date, several types of impaired interaction between the kidneys and the heart have been identified. The aim. To study the peculiarities of CRS in patients with IE complicated by AHF. Materials and methods. The basis of this study was the clinical data of 41 patients with active IE who were treated at the National Amosov Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine from 1/1/2020 to 8/31/2020. In order to study the features of clinical manifestation and the course of CRS, a comparative analysis was conducted based on the history and results of laboratory and instrumental research for the group of patients with IE complicated by preoperative AHF, and patients without clinical manifestations of AHF at the time of hospitalization. For an in-depth study of myocardial damage in heart failure, troponin, NT-proBNP, lactate levels were analyzed; dysfunction of the urinary system was assessed by the level of urea and serum creatinine, the volume of diuresis. Results. A reliable relationship between the levels of NT-proBNP and serum creatinine at the preoperative stage was revealed (p˂0.001), as an indicator of the presence of CRS in patients with IE. In the early postoperative period, signs of CRS persisted in patients with IE complicated by preoperative AHF (serum creatinine 157.0±8.5 μmol/l [p

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. [ABSTRACT FROM AUTHOR]

Background Cardiac troponins (cTn) are markers of myocardial injury with well established diagnostic value in adults. However, the benefits of using troponins in neonates with critical duct-dependent congenital cardiac diseases (cDD-CHDs) is questionable. Aim The study aimed to investigate the diagnostic role of cTnI in cDD-CHDs as a marker of myocardial injury and to explore its role in patient's outcome. Methods A case-control study, conducted over 80 neonates; Group I: Forty neonates with cDD-CHDs and Group II: Forty healthy neonates. CBC, CRP, electrolytes, liver and kidney functions, cTnI and echocardiography were done for both groups in first week of life. Then serum level of cTnI were re-evaluated after 3 weeks from initial sampling. Results The mean value of serum cTnI was significantly higher among cases when compared to controls (0.91±1.88 ng/ml versus 0.003±0.006 ng/ml, P<0.001*). The diagnostic performance of cTn I for cardiac injury was at cut-off 0.03 ng/ml with sensitivity 65% and specificity 97.5%. However, the prognostic role of cTnI in predicting death was at serum level of 0.7 ng/ml with 61% sensitivity and 81% specificity. cTn I in cDD-CHD was positively correlated to the severity of heart failure (HF) based on Modified Ross Score. The mean value of survival of the cDD-CHDs neonates was 28.11 days when cTnI is >0.6 ng/ml. Conclusion Initial serum levels of cTnI of cDD-CHD neonates in first week of life might be a useful marker in predicting the 40-days-survival and outcome. [ABSTRACT FROM AUTHOR]

Asprosin is a newly discovered protein hormone that promotes appetite, regulates glucose homeostasis, increases insulin resistance and has potential myocardial protection. Myocardium is vulnerable to oxidative stress injury caused by factors such as high glucose, anti‑tumor drugs, ischemia reperfusion and so on, and currently there is a lack of effective preventive measures. It has been reported in the literature that Asprosin has a unique protective effect on myocardium, but the protective mechanism of Asprosin is not clear. In this paper, the general situation and functions of Asprosin, as well as the protective mechanism of Asprosin on myocardium were reviewed, in order to provide reference for the application of Asprosin in the treatment of cardio‑related diseases. [ABSTRACT FROM AUTHOR]

Chloroacetyl chloride is a potent acylation agent that decomposes violently in water to produce chloroacetic acid and irritant hydrogen chloride. It and its decomposition products are corrosive to the eyes, skin, and respiratory system and can cause multiple organ failure. Herein, we report cases of poisoning by chloroacetyl chloride and its decomposition products in the skin and respiratory system. After exposure, one patient developed vomiting, irritability, coma, hypoxemia, hypotension, acidosis, and hypokalemia. Another patient developed bronchiolitis, pneumonia, and decreased vision. One patient died and two recovered. Chloroacetyl chloride and its decomposition products are corrosive and can damage multiple organs after absorption through the skin and respiratory tract, leading to severe heart failure. Cardiogenic shock may be the primary cause of early mortality.

Sepsis is defined as “a life-threatening organ dysfunction caused by a dysregulated host response to infection”. Although the treatment of sepsis has evolved rapidly in the last few years, the morbidity and mortality of sepsis in clinical treatment are still climbing. Sirtuins (SIRTs) are a highly conserved family of histone deacetylation involved in energy metabolism. There are many mechanisms of sepsis-induced myocardial damage, and more and more evidence show that SIRTs play a vital role in the occurrence and development of sepsis-induced myocardial damage, including the regulation of sepsis inflammation, oxidative stress and metabolic signals. This review describes our understanding of the molecular mechanisms and pathophysiology of sepsis-induced myocardial damage, with a focus on disrupted SIRTs regulation. In addition, this review also describes the research status of related therapeutic drugs, so as to provide reference for the treatment of sepsis.

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. [ABSTRACT FROM AUTHOR]

The use of cardiopulmonary bypass (CPB) is thought to cause delayed cardiac damage. DNA methylation-based liquid biopsies are novel biomarkers for monitoring acute cardiac cell death. We assessed cell-free DNA molecules as markers for cardiac damage after open-heart surgery. Novel cardiomyocyte-specific DNA methylation markers were applied to measure cardiac cfDNA in the plasma of 42 infants who underwent open-heart surgery. Cardiac cfDNA was elevated following surgery, reflecting direct surgery-related tissue damage, and declined thereafter in most patients. The concentration of cardiac cfDNA post-surgery correlated with the duration of CPB and aortic cross clamping. Strikingly, cardiac cfDNA at 6 h predicted duration of mechanical ventilation and maximal vasoactive-inotropic score better than did maximal troponin levels. Cardiac cfDNA reveals heart damage associated with CPB, and can be used to monitor cardiac cell death, to predict clinical outcome of surgery and to assess performance of cardioprotective interventions. [ABSTRACT FROM AUTHOR]

Isoproterenol (ISO) is widely used to treat bronchial asthma, cardiogenic or septic shock, complete atrioventricular block, and cardiac arrest. However, it can also cause myocardial damage owing to infarct-like necrosis. Curdione, an extract of the Chinese herb Rhizoma Curcumae, has a variety of pharmacological activities, including cardioprotective effects. In this study, we investigated the protective effects of curdione and its underlying mechanisms in an ISO-induced myocardial injury model. Our results showed that curdione attenuated ISO-induced H9c2 cell proliferation inhibition and lactic dehydrogenase (LDH) release. Curdione ameliorated morphological damage and reduced the ISO-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB) and LDH. Furthermore, curdione inhibited ISO-induced cell apoptosis, modulated the expression of Bcl-2 and Bax proteins, repealed the accumulation of ISO-induced reactive oxygen species (ROS), prevented mitochondrial dysfunction, and activated the Nrf2/SOD1/HO-1 signaling pathway. The above results show that curdione exerts a protective effect against ISO-induced myocardial damage by inhibiting apoptosis and oxidative stress, suggesting that curdione is a potential therapeutic strategy to prevent ISO-induced myocardial damage. [ABSTRACT FROM AUTHOR]