Myocardial Enzyme Levels Research Articles

Protective effect of Di'ao Xinxuekang capsule against doxorubicin-induced chronic cardiotoxicity

Ethnopharmacological relevanceDi'ao Xinxuekang capsule (DXXK) extracted from Dioscorea nipponica Makino is a well-known traditional Chinese herbal medicinal product widely used in the treatment of cardiovascular disease, such as myocardial ischemia and arrhythmia. The active ingredients of DXXK were also traditionally utilized for treating cardiovascular disease in the former Soviet Union after the 1960s. As a specific type of cardiovascular disease, doxorubicin (DOX)-induced cardiotoxicity is characterized by arrhythmia, myocardial ischemia, and heart failure. Aim of the studyThis study aimed to investigate the potential protective effect of DXXK against chronic cardiotoxicity induced by DOX. Materials and methodsA mouse model of chronic cardiotoxicity induced by DOX and an in vitro model of DOX-induced myocardial damage were created to assess the protective effect of DXXK. Cardiac functional parameters, serum levels of CK-MB and LDH and cardiac histopathological indicators were determined in the mouse model. Moreover, cell viability was measured by the MTT method, and the effect of DXXK on the anticancer activity of DOX was also investigated by utilizing 4T1, HepG2, and H460 cell lines. Furthermore, the levels of markers of oxidative stress indexes (SOD, GSH, MDA) and inflammation (TNF-α, IL-1α) were measured using biochemical and Elisa kits, respectively. The level of ROS in H9c2 cardiomyocyte was determined by flow cytometry. The protein expression levels of HIF-1α and NF-κB p65 were measured by western blotting. Finally, molecular docking was performed to visualize the patterns of interactions between the effective molecule and targeted protein. ResultsDXXK alleviated DOX-induced chronic cardiotoxicity as shown by the reversal of changes in levels of myocardial enzymes and left ventricular function and structure. DXXK exhibits antioxidant and anti-inflammatory activities. We also observed that DXXK might increase the protein expression level of HIF-1α and decrease the protein expression level of NF-κB p65. Further results of in vitro experiments showed that DXXK could protect cardiomyocyte against DOX-induced production of ROS, but DXXK had no effect on the anticancer activity of DOX. The results of molecular docking showed that dioscin and pseudoprotodioscin were the top two compounds of DXXK, which had high affinity with HIF-1α and NF-κB p65. ConclusionsOur results indicated that DXXK could protect against cardiotoxicity induced by DOX and alleviate oxidative stress and inflammation in vivo and in vitro via the regulation of HIF-1α and down NF-κB p65.

Exosomal microRNA-98-5p from hypoxic bone marrow mesenchymal stem cells inhibits myocardial ischemia–reperfusion injury by reducing TLR4 and activating the PI3K/Akt signaling pathway

ObjectiveMicroRNAs (miRNAs) are essential biomarkers during development of human diseases. We aimed to explore the role of hypoxia-induced bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-98-5p in myocardial ischemia–reperfusion injury (MI/RI). MethodsBMSCs were isolated, cultured, stimulated by hypoxia and transfected with adenovirus expressing miR-98-5p. The exosomes were extracted from BMSCs and named as BMSC-exos. The rat MI/RI models were established by ligation of left anterior descending artery and were respectively injected. Then, hemodynamic indices, myocardial enzymes, oxidative stress factors, inflammatory factors, macrophage infiltration and infarct size in these rats were determined. Expression of miR-98-5p, toll-like receptor 4 (TLR4) and the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway-related proteins was assessed. The target relation between miR-98-5p and TLR4 was confirmed by bioinformatic method and dual luciferase report gene assay. ResultsMiR-98-5p was downregulated, TLR4 was upregulated and the PI3K/Akt signaling pathway was inactivated in MI/RI rat myocardial tissues. Exosomal miR-98-5p from hypoxic BMSCs promoted cardiac function and suppressed myocardial enzyme levels, oxidative stress, inflammation response, macrophage infiltration and infarct size in I/R myocardial tissues. Moreover, TRL4 was targeted by miR-98-5p and miR-98-5p activated PI3K/Akt signaling pathway. ConclusionHypoxia-induced BMSC-exos elevated miR-98-5p to protect against MI/RI. This study may be helpful for treatment of MI/RI.

Dynamic observation of 5-fluorouracil-induced myocardial injury and mitochondrial autophagy in aging rats.

Patients treated with 5-fluorouracil (5-FU) can develop rare but potentially severe cardiac effects, including cardiomyopathy, angina pectoris, heart failure and cardiogenic shock. The specific pathologies and underlying mechanisms are yet to be fully understood. The results of previous studies have indicated that mitochondrial autophagy is widely detected in many angiocardiopathies. In the present study, the dynamic changes in the homeostasis of mitochondrial injury and autophagy were observed in rats treated with 5-FU for different durations. A corresponding control group and a 5-FU model group were established in groups of Sprague-Dawley rats aged 2 and 18 months, and the myocardial enzyme levels were determined at different time points. At 2 weeks post-model establishment, cardiac ultrasound and myocardial histological staining were performed, cardiomyocyte apoptosis and myocardial mitochondrial function were assessed, and mitochondrial ultrastructure was examined. In addition, the expression levels of autophagy-related proteins were evaluated in the 18-month-old rats on days 7 and 14 of 5-FU administration. The experimental results demonstrated that 5-FU induced an elevation in the levels of myocardial enzymes, as well as changes in the cardiac structure and function, and that these changes were more prominent over longer drug durations. In addition, 5-FU decreased the levels of myocardial mitochondrial ATP and mitochondrial membrane potential, and aggravated myocardial fibrosis and cardiomyocyte apoptosis compared with those observed in the untreated control group, treated with the same volume of saline as 5-FU in the 5-FU group. These injuries were particularly evident in aging rats. Notably, 5-FU increased the expression levels of myocardial mitochondrial autophagy-related proteins, and electron microscopy revealed a more severe autophagic state in the model groups compared with that in the control groups. In conclusion, 5-FU induced myocardial mitochondrial damage, the degree of which was more severe in aging rats compared with that in young rats. The mitochondrial autophagy induced by 5-FU was excessive, and the degree of autophagy was aggravated with increased 5-FU administration time.

Mechanisms of Paeoniflorin against myocardial ischemia reperfusion injury based on network pharmacology

Ischemic heart disease (IHD) is the primary reason of death of cardiovascular diseases. Paeoniflorin (PF), a monoterpene glycoside extracted from Radix Paeoniae Rubra or Paeoniae Radix Alba, can ameliorate myocardial ischemia/reperfusion injury (MIRI), but its mechanism is not still defined. In this study, network pharmacology was utilized, the protein interaction network between PF and MIRI targets were screened for bioenrichment analysis. Moreover, the anti-MIRI effects of PF (30, 60 and 120 mg/kg) were investigated in vivo on rats for verification. The myocardial infarction area was assessed by TTC/Evans blue staining and morphological changes of tissues were evaluated using hematoxylin and eosin staining. The contents of myocardial enzymes and oxidation resistance were measured. The cell apoptosis was evaluated using TUNEL staining and the expression of proteins was estimated using Western Blot. In the results, the relevant targets and the biological processes of PF against MIRI were screened out, indicating its anti-MIRI potential pharmacological effects of PF. 120 mg/kg PF can shrink infarction area after ischemia/reperfusion, ameliorate pathological morphology in myocardial tissue, lower the levels of myocardial enzymes, and attenuate oxidative stress. Furthermore, PF could reduce the positive rate of TUNEL staining caused by MIRI. Moreover, 120 mg/kg PF could depress the protein levels of Bax, Caspase-3, Beclin-1 and Cathepsin B and increase the protein level of Bcl-2 on rats after reperfusion. In conclusion, Paeoniflorin has an anti-MIRI effect in rats via coordinate regulation of anti-oxidative stress, anti-apoptosis and inhibition of autophagy.

Radioprotective Effect of Thymoquinone in X-irradiated Rats.

Background:Thymoquinone, has anti-inflammatory, anti-oxidant, and cardio protection properties. This study aimed to evaluate the radioprotective effect of thymoquinone in whole body X-irradiated rats. Methods:This study conducted on 40 male adult Wistar albino rats randomized into the following groups: Group I: Control rats did not receive thymoquinone or ionizing radiation. Group II: Whole-body irradiated rats with 6 Gy of X-ray. Group III: Rats orally intubated with thymoquinone (10 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone for another 7 days. Group IV: Rats orally intubated with thymoquinone (20 mg/kg/day) for 7 days then subjected to whole-body irradiation with 6 Gy then supplemented with thymoquinone (20 mg/kg/day) for another 7 days. LDH, CK-MB, ALT, AST, MDA, TAC, Catalase activity, GPX, GSR and GSH were measured. Results:Lipid peroxidation biomarker in the blood of X-irradiated rats significantly increased and accompanied by decrease in the levels of GSH, GSR, GPX, catalase as well as TAC. Moreover, exposure to IR significantly increases cardiac and liver enzymes. However, administration of TQ to X-irradiated rats with either 10 mg/kg or 20 mg/kg have the same reform effects and significantly protects rats against adverse effects of IR. Conclusion:Exposure to X-ray leads to significant changes in cellular biochemical and morphological conditions. Administration of TQ before radiation treatment significantly decreases the adverse effects of IR. TQ can improve cardiac function, decrease myocardial enzyme levels and inhibit oxidative stress.

Clemastine Fumarate Attenuates Myocardial Ischemia Reperfusion Injury Through Inhibition of Mast Cell Degranulation.

Mast cell (MC) activation is associated with myocardial ischemia reperfusion injury (MIRI). Suppression of MC degranulation might be a target of anti-MIRI. This study aimed to determine whether clemastine fumarate (CLE) could attenuate MIRI by inhibiting MC degranulation. A rat ischemia and reperfusion (I/R) model was established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Compound 48/80 (C48/80) was used to promote MC degranulation. The protective effect of CLE by inhibiting MC degranulation on I/R injury was detected by cardiac function, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, arrhythmia, and myocardial enzyme detection. Inflammatory factor mRNA levels, such as TNF-α, interleukin (IL)-1β, and IL-6, were detected. Cultured RBL-2H3 mast cells were pretreated with CLE and subjected to C48/80 treatment to determine whether CLE suppressed MC degranulation. Degranulation of MCs was visualized using tryptase release, Cell Counting Kit-8 (CCK-8), and cell toluidine blue (TB) staining. RBL cells were conditionally cultured with H9C2 cells to explore whether CLE could reverse the apoptosis of cardiomyocytes induced by MC degranulation. Apoptosis of H9C2 cells was detected by CCK-8, the LDH Cytotoxicity Assay Kit (LDH), TUNEL staining, and protein expression of BAX and Bcl-2. We found that CLE pretreatment further inhibited cardiac injury manifested by decreased infarct size, histopathological changes, arrhythmias, MC degranulation, and myocardial enzyme levels, improving cardiac function compared with that in the I/R group. C48/80 combined with I/R exacerbated these changes. However, pretreatment with CLE for C48/80 combined with I/R significantly reversed these injuries. In addition, CLE pretreatment improved the vitality of RBL cells and reduced tryptase release in vitro. Similarly, the supernatant of RBL cells pretreated with CLE decreased the cytotoxicity, TUNEL-positive cell rate, and BAX expression of conditioned H9C2 cells and increased the cell vitality and expression of Bcl-2. These results suggested that pretreatment with CLE confers protection against I/R injury by inhibiting MC degranulation.

A Single-Center (Sibiu, Romania), Retrospective Study (March-November 2020) of COVID-19 Clinical and Epidemiological Features in Children.

The aim of this study was to describe and analyze epidemiological and clinical features of children screened for COVID-19 at Sibiu Pediatric Clinical Hospital during the first 9 months (March–November) of coronavirus disease pandemic in Romania. A total of 203 pediatric patients with a confirmed diagnosis of COVID-19 were included in the study. The median age of the patients was 121 (IQR 18–181) months and 52.22% had mild clinical type with pneumonia, 35.47% were moderate cases, 3.94% severe cases, 0.99% critically ill cases and 7.39% were asymptomatic. The most common symptoms were fever (n = 130, 64.03%), nasal congestion (n = 138, 67.98%), cough (n = 128, 63.05%) followed by sore throat (n = 64, 31.52%), rhinorrhea (n = 63, 31.03%), fatigue (n = 57, 28.07%), headache (n = 47, 23.15%), diarrhea (n = 39, 19.21%), vomiting (n = 32, 15.76%), myalgia (n = 24, 11.82%), abdominal pain (n = 22, 10.83%). A higher proportion of infants with severe or critical disease was encountered with lymphopenia (n = 9, 90%), neutrophilia (n = 5, 50%), leukocytosis (n = 5, 50%) compared with asymptomatic infants (n = 10, 66.67%, n = 1, 6.67%, n = 3, 20%) or mild (n = 53, 50%, n = 19, 17.92%, n = 15, 14.15%) and moderate (n = 37, 51.39%, n = 9, 12.50%, n = 6, 8.33%) cases (p = 0.095, p = 0.042, p = 0.034). Pediatric patients generally had mild or moderate type of COVID-19, and the critically ill cases were rare. In our study, frequent symptoms were observed in both the systemic and respiratory systems, ear, nose and throat system, and less from gastrointestinal system, central nervous system or ocular system. Additionally, there is an increase in liver and myocardial enzyme levels with an increase in disease severity. Understanding the clinical and laboratory characteristics of pediatric patients is important for diagnosis, management and effective control of the disease.

Naringin attenuates rat myocardial ischemia/reperfusion injury via PI3K/Akt pathway-mediated inhibition of apoptosis, oxidative stress and autophagy.

Naringin (NRG) has been reported to exert cardioprotective effects against multiple cardiovascular diseases, including lipopolysaccharide-induced and hyperglycemia-induced myocardial injury. However, the role of NRG in myocardial ischemia/reperfusion (I/R) injury remains unclear. In the present study, the PI3K/Akt pathway was investigated to evaluate the possible mechanisms underlying the roles of NRG in myocardial ischemia/reperfusion (I/R) injury. The levels of cardiac enzymes were measured by ELISA to evaluate the optimal dosage of NRG that could protect against myocardial I/R injury. Rats were administered 100 mg/kg of NRG and activities of myocardial enzymes, the level of cardiac apoptosis and inflammation, oxidant response, autophagy indicators and echocardiography were evaluated. The level of corresponding proteins was measured using western blotting. The results indicated that NRG elicited the best cardioprotective effects at a dose of 100 mg/kg by significantly reducing the levels of myocardial enzymes, apoptosis, inflammation, oxidative response and infarct size. Furthermore, NRG alleviated contractile dysfunction by increasing the left ventricular ejection fraction and fractional shortening. In addition, NRG markedly promoted the phosphorylation of Akt, while decreasing the level of autophagy indicator beclin-1 and the microtubule-associated protein 1B-light chain 3 (LC3B) II/ LC3BI ratio. However, PI3K/Akt inhibitor (LY294002) partially reduced the NRG induced phosphorylation of Akt and the reduction in beclin-1, along with the LC3BII/LC3BI ratio. The results of the present study demonstrated that NRG could attenuate myocardial I/R injury.

Guan Xin Dan Shen formulation protects db/db mice against diabetic cardiomyopathy via activation of Nrf2 signaling.

Guan Xin Dan Shen formulation (GXDSF) is a widely used treatment for the management of coronary heart disease in China and is composed of three primary components: Dalbergiae odoriferae Lignum, Salviae miltiorrhizae Radix et Rhizoma and Panax notoginseng Radix et Rhizoma. However, the potential use of GXDSF for the management of diabetic cardiomyopathy (DCM) has not been previously assessed. The present study aimed to assess the effects of GXDSF on DCM, as well as the underlying mechanism. In the present study, db/db mice were used. Following treatment with GXDSF for 10 weeks, fasting blood glucose, insulin sensitivity, serum lipid levels and cardiac enzyme levels were detected. Cardiac pathological alterations and cardiac function were assessed by performing hematoxylin and eosin staining and echocardiograms, respectively. TUNEL assays were conducted to assess cardiomyocyte apoptosis. Additionally, reverse transcription-quantitative PCR and western blotting were performed to evaluate the expression of apoptosis-associated genes and proteins, respectively. In the model group, the db/db mice displayed obesity, hyperlipidemia and hyperglycemia, accompanied by noticeable myocardial hypertrophy and diastolic dysfunction. Following treatment with GXDSF for 10 weeks, serum triglyceride levels were lower and insulin sensitivity was enhanced in db/db mice compared with the model group, which indicated improvement in condition. Cardiac hypertrophy and dysfunction were also improved in db/db mice following treatment with GXDSF, resulting in significantly increased left ventricular ejection fraction and fractional shortening compared with the model group. Following treatment with metformin or GXDSF, model-induced increases in levels of myocardial enzymes were decreased in the moderate and high dose groups. Moreover, the results indicated that, compared with the model group, GXDSF significantly inhibited cardiomyocyte apoptosis in diabetic heart tissues by increasing Bcl-2 expression and decreasing the expression levels of Bax, cleaved caspase-3 and cleaved caspase-9. Mechanistically, GXDSF enhanced Akt phosphorylation, which upregulated antioxidant enzymes mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Collectively, the results of the present study indicated that GXDSF attenuated cardiac dysfunction and inhibited cardiomyocyte apoptosis in diabetic mice via activation of Akt/Nrf2 signaling. Therefore, GXDSF may serve as a potential therapeutic agent for the management of DCM.

Dexmedetomidine alleviates myocardial ischemia/reperfusion-induced injury and Ca2+ overload via the microRNA-346-3p/CaMKIId axis

Myocardial ischemia/reperfusion (MI/R) may impair cardiac functions. Dexmedetomidine (DEX) is protective in various clinical cases. Therefore, this study investigated the role and mechanism of DEX in MI/R. The myocardial infarct size, apoptosis, and levels of myocardial enzymes, SOD, ROS, Ca2+, and inflammatory factors in DEX-treated MI/R rats were measured. Differentially expressed microRNAs (miRs) in DEX-treated MI/R rats were detected. miR-346-3p was intervened to assess the effects of DEX on MI/R rats. The targeted binding relationship between miR-346-3p and CaMKIId was predicted and verified. DEX effect on hypoxia/reoxygenation (H/R)-induced cell model was evaluated. The role of CaMKIId in DEX protection was assessed after CaMKIId overexpression in H/R cells. NF-κB pathway and NLRP3 inflammasome-related protein levels were detected. DEX alleviated the myocardial injury and Ca2+ overload in MI/R rats, as evidenced by reduced infarct size, apoptosis and levels of myocardial enzymes, ROS, Ca2+, and inflammatory factors. DEX promoted miR-346-3p expression in MI/R rats, and miR-346-3p knockdown reversed DEX protection on MI/R rats. miR-346-3p targeted CaMKIId. DEX improved H/R-induced cell injury and Ca2+ overload and inhibited NF-κB/NLRP3 inflammasome-related protein levels, which were all reversed by CaMKIId overexpression. DEX alleviated injury and Ca2+ overload in MI/R via regulating the miR-346-3p/CaMKIId axis and inhibiting the NF-κB/NLRP3 inflammasome pathway.

Tetrandrine Ameliorates Myocardial Ischemia Reperfusion Injury through miR-202-5p/TRPV2.

Objective This study is aimed at investigating the therapeutic effects of tetrandrine (Tet) on myocardial ischemia reperfusion (I/R) injury and probe into underlying molecular mechanism. Methods H9C2 cells were divided into hypoxia/oxygenation (H/R) group, H/R+Tet group, H/R+Tet+negative control (NC) group, and H/R+Tet+miR-202-5p inhibitor group. RT-qPCR was utilized to monitor miR-202-5p and TRPV2 expression, and TRPV2 protein expression was detected via western blot and immunohistochemistry in H9C2 cells. Cardiomyocyte apoptosis was evaluated through detection of apoptosis-related markers and flow cytometry. Furthermore, myocardial enzyme levels were detected by ELISA. Rats were randomly separated into sham operation group, I/R group, I/R+Tet group (50 mg/kg), I/R+Tet+NC group, and I/R+Tet+miR-202-5p inhibitor group. miR-202-5p and TRPV2 mRNA expression was assessed by RT-qPCR. TRPV2 protein expression was detected through western blot and immunohistochemistry in myocardial tissues. Apoptotic levels were assessed via apoptosis-related proteins and TUNEL. Pathological changes were observed by H&E staining. Myocardial infarction size was examined by Evans blue-TCC staining. Results Abnormally expressed miR-202-5p as well as TRPV2 was found in H/R H9C2 cells and myocardial tissues of I/R rats, which was ameliorated following Tet treatment. Tet treatment significantly suppressed H/R- or I/R-induced cardiomyocyte apoptosis. ELISA results showed that CK-MB and LDH levels were lowered by Tet treatment in H/R H9C2 cells and serum of I/R rats. H&E staining indicated that Tet reduced myocardial injury in I/R rats. Also, myocardial infarction size was lowered by Tet treatment. The treatment effects of Tet were altered following cotreatment with miR-202-5p inhibitor. Conclusion Our findings revealed that Tet may ameliorate myocardial I/R damage via targeting the miR-202-5p/TRPV2 axis.

Clinical features of cardiac lymphoma: an analysis of 37 cases.

ObjectiveTo summarize the clinical and pathological features of patients with cardiac lymphoma.MethodsThe general conditions, clinical features, pathological types, and prognostic indices of 37 patients with cardiac lymphoma treated in our hospital were analyzed.ResultsAmong the 37 patients, only one had primary cardiac lymphoma, and the other 36 patients had secondary cardiac lymphoma. The cardiac manifestations were mainly chest tightness, shortness of breath, increased heart rates, and electrocardiographic abnormality caused by pericardial effusion, but myocardial enzyme levels were normal in all patients. Only three patients displayed solid heart-occupying manifestations. These lesions were mainly located in the right atrium, and the masses were all larger than 5 cm. The pathological type was diffuse large B cell lymphoma that did not arise from the germinal center in all three patients.ConclusionsCardiac lymphoma was mostly secondary, and pericardial effusion was the primary objective sign. Moreover, cardiac lymphoma was characterized by a high international prognostic index, late stage, and high rates of T and NK cell lymphoma. Most cases were accompanied by serous cavity effusion, extranodal involvement of important organs, elevated lactate dehydrogenase levels, hypoalbuminemia, and normal myocardial enzyme levels.

Protective effect of sevoflurane on vascular endothelial glycocalyx in patients undergoing heart valve surgery: A randomised controlled trial.

The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. Randomised controlled study. Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. Fifty-one patients. After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

Comparison between Different Tricuspid Valve Procedures through Postoperative Inflammation and Myocardial Enzymes.

IntroductionThe thoracoscopic procedure for tricuspid valve (TV) diseases is a minimally invasive method of treatment. This study focuses on comparing the changes in postoperative inflammatory reaction and myocardial injury markers after thoracoscopic and sternotomy/thoracotomy TV procedures.MethodsWe retrospectively analyzed 88 patients (53 males, aged 50.9±16.2 years) with TV diseases (single-valve disease) (72 cases of TV plasty) between January 2018 and April 2019. A total of 56 patients underwent thoracoscopic procedure (50 cases of TV plasty). The leukocyte and C-reactive protein (CRP) levels were monitored as indicators of systemic inflammatory reaction. The lactate dehydrogenase, creatine kinase, creatine kinase myocardial band, aspartate aminotransferase, and troponin-T levels were recorded as markers of myocardial injury.ResultsThe CRP and white blood cells levels of patients in the sternotomy approach group were continuously higher than those in patients in the thoracoscopic approach group. And the levels of myocardial enzymes in patients in the thoracoscopic approach group were significantly lower than those in patients in the sternotomy approach group.ConclusionCompared with sternotomy/thoracotomy procedures on TV, the thoracoscopic procedure can reduce postoperative myocardial injury significantly and systemic inflammatory reaction to a certain extent. It is technically feasible, safe, effective, and worthy of widespread adoption in clinical practice.

The Effect of Amlodipine Combined with Atorvastatin on the Levels of HMGB-1 and YKL-40 in Patients with Coronary Heart Disease and Carotid Atherosclerosis

To observe the incidence of adverse reactions of amlodipine combined with atorvastatin in patients with coronary heart disease complicated with carotid atherosclerosis and the effect on the levels of high-mobility group box protein 1 and human cartilage glycoprotein 39. Retrospective analyses of patients with coronary heart disease combined with carotid atherosclerosis in our hospital are divided into two groups according to different treatment methods. The control group was given atorvastatin and the observation group was given amlodipine on this basis. The differences in blood lipid levels, myocardial enzyme levels, intima-media thickness levels, high-mobility group box protein 1 and human cartilage glycoprotein 39 changes before and after treatment were compared between the two groups. During the treatment period, there was no difference in the incidence of complications between the two groups. There was no difference in blood lipid levels between the two groups before treatment. After treatment, the levels of low-density lipoprotein cholesterol, triglycerides and total cholesterol in the observation group were lower than those in the control group and the levels of high-density lipoprotein cholesterol were higher than those in the control group. There was no difference in intima-media thickness before treatment between the two groups. At 4 and 8 w after treatment, the intima-media thickness value of the observation group was lower than that of the control group (p<0.05). There was no difference in the levels of high-mobility group box protein 1 and human cartilage glycoprotein 39 between the two groups before treatment. After treatment, the levels of high-mobility group box protein 1 and human cartilage glycoprotein 39 in the observation group were lower than those in the control group (p<0.001). There was no difference in myocardial enzyme indexes between the two groups before treatment. After treatment, the levels of lactate dehydrogenase and creatine kinase myocardial band of the two groups were lower than before treatment and the observation group was lower than the control group, the difference was statistically significant (p<0.001). Amlodipine combined with atorvastatin has a good therapeutic effect on patients with coronary heart disease complicated with carotid atherosclerosis and has good application value.

Hydroxysafflor Yellow A Ameliorates Myocardial Ischemia/Reperfusion Injury by Suppressing Calcium Overload and Apoptosis.

Myocardial ischemia/reperfusion injury (MI/RI) is an urgent problem with a great impact on health globally. However, its pathological mechanisms have not been fully elucidated. Hydroxysafflor yellow A (HSYA) has a protective effect against MI/RI. This study is aimed at further clarifying the relationship between HSYA cardioprotection and calcium overload as well as the underlying mechanisms. We verified the protective effect of HSYA on neonatal rat primary cardiomyocytes (NPCMs) and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from hypoxia-reoxygenation (HR) injury. To explore the cardioprotective mechanism of HSYA, we employed calcium fluorescence, TUNEL assay, JC-1 staining, and western blotting. Finally, cardio-ECR and patch-clamp experiments were used to explain the regulation of L-type calcium channels (LTCC) in cardioprotection mediated by HSYA. The results showed that HSYA reduced the levels of myocardial enzymes and protected NPCMs from HR injury. HSYA also restored the contractile function of hiPSC-CMs and field potential signal abnormalities caused by HR and exerted a protective effect on cardiac function. Further, we demonstrated that HSYA protects cardiomyocytes from HR injury by decreasing mitochondrial membrane potential and inhibiting apoptosis and calcium overload. Patch-clamp results revealed that MI/RI caused a sharp increase in calcium currents, which was inhibited by pretreatment with HSYA. Furthermore, we found that HSYA restored contraction amplitude, beat rate, and field potential duration of hiPSC-CMs, which were disrupted by the LTCC agonist Bay-K8644. Patch-clamp experiments also showed that HSYA inhibits Bay-K8644-induced calcium current, with an effect similar to that of the LTCC inhibitor nisoldipine. Therefore, our data suggest that HSYA targets LTCC to inhibit calcium overload and apoptosis of cardiomyocytes, thereby exerting a cardioprotective effect and reducing MI/RI injury.

Kuanxiong aerosol inhibits apoptosis and attenuates isoproterenol-induced myocardial injury through the mitogen-activated protein kinase pathway

Ethnopharmacological relevanceKuanxiong aerosol (KXA) is a common clinical drug based on Fangxiang Wentong (FXWT) therapy in the treatment of angina pectoris. However, the pharmacological mechanism of KXA in the prevention and treatment of myocardial injury (MI) is not clear. Aim of the studyThe purpose of this study was to explore the protective effect of KXA on isoproterenol (ISO)-induced MI in rats. Materials and methodsThe study included male Wistar Kyoto rats (age: 6 weeks). The rats were randomly divided into the following 5 groups (n = 6 per group): control group, ISO group, isosorbide mononitrate (ISMN) group (5 mg/kg), KXA-L group (0.1 mL/kg), and KXA-H group (0.3 mL/kg). The rats in the last three groups were given intragastric administration for 14 days, and rats in control group and ISO group were given the same amount of normal saline daily. ISO (120 mg/kg) was used to induce MI on the 13th and 14th days. We assessed electrocardiograms (ECGs), myocardial specific enzymes, histopathological changes, and apoptosis. ResultsWe found that KXA reduced the increase in the ST-segment amplitude (elevation or depression) and the levels of myocardial marker enzymes induced by ISO in MI rats, improved the pathological changes in myocardial tissue, and reduced cardiomyocyte apoptosis. At the same time, KXA significantly inhibited the up-regulation of caspase-3 and Bax expression and down-regulation of Bcl-2 expression induced by ISO. RNA sequencing showed that 90 up-regulated genes induced by ISO were down-regulated after KXA treatment, whereas 27 down-regulated genes induced by ISO were up-regulated after KXA treatment. In addition, KEGG pathway enrichment analysis showed that the mitogen-activated protein kinase (MAPK) signaling pathway may be an important target of KXA in the treatment of ISO-induced MI in rats. The results of RNA sequencing verified by Western blot analysis showed that KXA significantly inhibited the activation of the ISO-induced MAPK pathway. ConclusionsKXA improves cardiac function in MI rats by inhibiting apoptosis mediated by the MAPK signaling pathway.

Predictors of mechanical ventilation for COVID-19: combined data from three designated hospitals.

Whether patients with COVID-19 require invasive mechanical ventilation (MV) is not yet clear. This article summarizes the clinical treatment process and clinical data of patients with COVID-19 and analyzes the predictive factors for mechanical ventilation for these patients. A retrospective study was carried out from January 5, 2020, to March 23, 2020, including 98 patients with COVID-19 treated at three designated hospitals in Huangshi City, Hubei Province. Data collection included demographics, previous underlying diseases, clinical manifestations, laboratory examinations, imaging examination results, diagnosis, and prognosis. This study presents a summary of the patients' overall clinical characteristics and clarifies the predictive factors for MV in patients with COVID-19. There were 56 males and 42 females included in this study. The mortality rate was 26.53% (26/98). Fever, cough, and chest tightness were the most common symptoms (64.3%, 37.8%, and 12.2%, respectively). Thirty cases required MV, 30.61% of the total cases, and the mortality rate was 73.33%. The univariate comparison showed that dyspnea, acute physiologic assessment, chronic health evaluation (APACHE II) score, and the ratio between arterial blood oxygen partial pressure (PaO2) and oxygen concentration (FiO2) (P/F) were statistically different between the MV group and the non-MV group (p < 0.05). Results showed the following: dyspnea; increased white blood cell count; decreased platelets; lowered albumin levels; increased urea nitrogen; increased levels of myocardial enzymes Creatine Kinase (CK), Creatine Kinase, MB Form (CKMB) and lactate dehydrogenase (LDH); increased lactate, and lowered blood calcium tests. These findings may indicate that the patients have an increased probability of needing MV support. A cutoff value for the initial APACHE II score of >11.5 and the initial PaO2/FiO2 ratio of <122.17 mmHg should be considered for MV support for patients with COVID-19.

Acute Myocarditis Related to COVID-19: Comparison to SARS and MERS.

Myocardial involvement has been described during previous SARS and MERS outbreaks. Infection by SARS-CoV-2 (COVID-19) can range from asymptomatic to life-threatening multi-system disease. Heart involvement most commonly occurs during severe COVID-19 infection. Myocardial injury, based on elevated levels of myocardial enzymes, has been noted in up to 30% of patients with COVID-19 infection and could be a marker for worse prognosis. A few cases of possible myocarditis due to SARS-CoV-2 have been described, providing variable degree of evidence of direct myocardial involvement. We reviewed in detail those cases in comparison to relevant literature on SARS and MERS and attempted to draw initial conclusions in regard to clinical presentation, treatment and prognosis.

Calenduloside E suppresses calcium overload by promoting the interaction between L-type calcium channels and Bcl2-associated athanogene 3 to alleviate myocardial ischemia/reperfusion injury

IntroductionIntracellular calcium overload is an important contributor to myocardial ischemia/reperfusion (MI/R) injury. Total saponins of the traditional Chinese medicinal plant Aralia elata (Miq.) Seem. (AS) are beneficial for treating MI/R injury, and Calenduloside E (CE) is the main active ingredient of AS. ObjectivesThis study aimed to investigate the effects of CE on MI/R injury and determine its specific regulatory mechanisms. MethodsTo verify whether CE mediated cardiac protection in vivo and in vitro, we performed MI/R surgery in SD rats and subjected neonatal rat ventricular myocytes (NRVMs) to hypoxia-reoxygenation (HR). CE’s cardioprotective against MI/R injury was detected by Evans blue/TTC staining, echocardiography, HE staining, myocardial enzyme levels. Impedance and field potential recording, and patch-clamp techniques of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to detect the function of L-type calcium channels (LTCC). The mechanisms underlying between CE and LTCC was studied through western blot, immunofluorescence, and immunohistochemistry. Drug affinity responsive target stability (DARTS) and co-immunoprecipitation (co-IP) used to further clarify the effect of CE on LTCC and BAG3. ResultsWe found that CE protected against MI/R injury by inhibiting calcium overload. Furthermore, CE improved contraction and field potential signals of hiPSC-CMs and restored sarcomere contraction and calcium transient of adult rat ventricular myocytes (ARVMs). Moreover, patch-clamp data showed that CE suppressed increased L-type calcium current (ICa,L) caused by LTCC agonist, proving that CE could regulate calcium homeostasis through LTCC. Importantly, we found that CE promoted the interaction between LTCC and Bcl2-associated athanogene 3 (BAG3) by co-IP and DARTS. ConclusionOur results demonstrate that CE enhanced LTCC-BAG3 interaction to reduce MI/R induced-calcium overload, exerting a cardioprotective effect.