This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

This study employed a mouse model of coronary artery ligation to assess the effect and mechanism of Jiming Powder on mitochondrial autophagy in mice with myocardial infarction. The mouse model of heart failure post-myocardial infarction was established by ligating the left anterior descending coronary artery. The pharmacological efficacy of Jiming Powder was evaluated through echocardiographic imaging, hematoxylin-eosin(HE) staining, and Masson staining. The levels of malondialdehyde(MDA), Fe~(2+), reduced glutathione(GSH), and superoxide dismutase(SOD) in heart tissues, as well as MDA immunofluorescence of heart tissues, were measured to assess lipid peroxidation and Fe~(2+) levels in the hearts of mice in different groups. Ferroptosis levels in the groups were evaluated using scanning electron microscopy and Prussian blue staining. Western blot analysis was conducted to detect the levels of key ferroptosis-related proteins, including nuclear factor erythroid 2-related factor 2(NRF2), ferritin heavy chain(FTH), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), heme oxygenase 1(HO-1), and Kelch-like ECH-associated protein 1(KEAP1). The results showed that compared with the model group, both the high-and low-dose Jiming Powder groups exhibited significantly reduced left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd), while the left ventricular ejection fraction(EF) and left ventricular fractional shortening(FS) were significantly improved, effectively enhancing cardiac function in mice post-myocardial infarction. HE staining revealed that Jiming Powder attenuated myocardial inflammatory cell infiltration post-infarction, and Masson staining indicated that Jiming Powder effectively reduced fibrosis in the infarct margin area. Treatment with Jiming Powder reduced the levels of MDA and Fe~(2+), indicators of lipid peroxidation post-myocardial infarction, while increasing GSH and SOD levels, thus protecting ischemic myocardium. Western blot results demonstrated that Jiming Powder reduced KEAP1 protein accumulation, activated the NRF2/HO-1/GPX4 pathway, and up-regulated the protein expression of FTH and SLC7A11, exerting an inhibitory effect on ferroptosis. This study reveals that Jiming Powder exerts a therapeutic effect on myocardial infarction by inhibiting ferroptosis through the NRF2/HO-1/GPX4 pathway, providing a foundation for subsequent research on the pharmacological effects of Jiming Powder.
Animals ; Ferroptosis/drug effects* ; Myocardial Infarction/physiopathology* ; NF-E2-Related Factor 2/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Heme Oxygenase-1/genetics* ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Humans ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Disease Models, Animal

OBJECTIVE: To study incident and clinical characteristics of the coronary microcirculation dysfunction (CMD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and to explore the predictive value of CMD for in-hospital acute heart failure event. METHODS: One hundred and forty five patients with AMI who had received PCI and completed MCE during hospitalization in Peking University People' s Hospital from November 2015 to July 2021 were enrolled in our study. The patients were divided into CMD group and normal group according to the coronary microcirculation status detected by MCE. Clinical data and MCE data of the two groups were collected and analyzed. The acute heart failure event during hospitalization was described. A multivariate Logistic regression model was built to analyze the risk of acute heart failure in patients with CMD. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of CMD in predicting acute heart failure event. RESULTS: CMD detected by MCE occurred in 87 patients (60%). Compared with normal group, patients with CMD had higher troponin I (TnI) peak level [52.8 (8.1, 84.0) μg/L vs. 18.9 (5.7, 56.1) μg/L, P=0.005], poorer Killip grade on admission (P=0.030), different culprit vessel (P < 0.001) and more patients had thrombolysis in myocardial infarction (TIMI) flow pre-PCI less than grade 3 in culprit vessel (65.1% vs. 43.1%, P=0.025). Meanwhile, patients with CMD had poorer left ventricular ejection fraction (LVEF) [52% (43%, 58%) vs. 61% (54%, 66%)], poorer global longitudinal strain (GLS) [-11.2% (-8.7%, -14.0%) vs.-13.9% (-10.8%, -17.0%)] and worse wall motion score index (WMSI) (1.58±0.36 vs. 1.25± 0.24) (P all < 0.001). Acute left heart failure happened in 13.8% of the CMD patients, which were significant higher than that in the patients with normal coronary microcirculation perfusion (1.7%, P=0.013). After correcting for the culprit vessel, the TIMI flow pre-PCI in the culprit vessel and the peak TnI value, the risk of acute left heart failure in the patients with CMD was still high (OR=9.120, 95%CI: 1.152-72.192, P=0.036). The area under ROC curve (AUC) was 0.677 (95%CI: 0.551-0.804, P=0.035). CONCLUSION The incidence of CMD detected by MCE in patients with AMI post-PCI was 60%. Patients with CMD have a higher risk of acute left heart failure during hospitalization.
Humans ; Heart Failure/physiopathology* ; Microcirculation ; Percutaneous Coronary Intervention/adverse effects* ; Myocardial Infarction/complications* ; Male ; Female ; Hospitalization ; Middle Aged ; Aged ; Echocardiography ; Coronary Circulation ; Predictive Value of Tests ; Troponin I/blood*

OBJECTIVE: To assess the cardioprotective effect and impact of Qishen Granules (QSG) on different ischemic areas of the myocardium in heart failure (HF) rats by evaluating its metabolic pattern, substrate utilization, and mechanistic modulation. METHODS: In vivo, echocardiography and histology were used to assess rat cardiac function; positron emission tomography was performed to assess the abundance of glucose metabolism in the ischemic border and remote areas of the heart; fatty acid metabolism and ATP production levels were assessed by hematologic and biochemical analyses. The above experiments evaluated the cardioprotective effect of QSG on left anterior descending ligation-induced HF in rats and the mode of energy metabolism modulation. In vitro, a hypoxia-induced H9C2 model was established, mitochondrial damage was evaluated by flow cytometry, and nuclear translocation of hypoxia-inducible factor-1 α (HIF-1 α) was observed by immunofluorescence to assess the mechanism of energy metabolism regulation by QSG in hypoxic and normoxia conditions. RESULTS: QSG regulated the pattern of glucose and fatty acid metabolism in the border and remote areas of the heart via the HIF-1 α pathway, and improved cardiac function in HF rats. Specifically, QSG promoted HIF-1 α expression and entry into the nucleus at high levels of hypoxia (P<0.05), thereby promoting increased compensatory glucose metabolism; while reducing nuclear accumulation of HIF-1 α at relatively low levels of hypoxia (P<0.05), promoting the increased lipid metabolism. CONCLUSIONS QSG regulates the protein stability of HIF-1 α, thereby coordinating energy supply balance between the ischemic border and remote areas of the myocardium. This alleviates the energy metabolism disorder caused by ischemic injury.
Animals ; Myocardial Infarction/physiopathology* ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Rats, Sprague-Dawley ; Glucose/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Energy Metabolism/drug effects* ; Rats ; Fatty Acids/metabolism* ; Myocardium/pathology*

The autonomic nervous system imbalance caused by the overactivation of the sympathetic nerve and the weakened activity of the parasympathetic nerve is closely related to the occurrence and development of myocardial infarction.Autonomic nerve regulation is a new therapeutic approach aiming at inhibiting sympathetic activity and increasing parasympathetic activity.It encompasses magnetic nerve stimulation,optogenetic neuromodulation,and microinjection of botulinum toxin,which could promote the rebalance of the autonomic nervous system,thereby curbing the deterioration of the cardiac function and reducing the occurrence of ventricular arrhythmias after myocardial infarction.This paper reviews the anatomical basis,mechanisms of action,and research advances in intervention strategies of the autonomic nervous system in myocardial infarction.
Humans ; Myocardial Infarction/physiopathology* ; Autonomic Nervous System/physiopathology* ; Autonomic Pathways

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network. The protein-protein interaction(PPI) network analysis was performed on STRING. R language was used for Gene Ontology(GO) and Kyoto Encycloperfia of Genes and Genomes(KEGG) enrichment analyses. Molecular docking was adopted to validate the core targets. The mouse model of MI-induced CHF was established by surgical ligation of the left anterior descending coronary artery. The modeled mice were assigned into the sham, model, low-, medium-, and high-dose(2.34, 4.68, and 9.36 g·kg~(-1), respectively) LGZGD, and captopril(3.25 mg·kg~(-1)) groups. After continuous administration for 6 weeks, a Doppler ultrasound imaging system was used to examine the heart function indicators: left ventricular ejection fraction(LVEF), left ventricular fractional shortening(LVFS), left ventricular end-systolic dimension(LVIDs), and left ventricular end-diastolic dimension(LVIDd). The myocardial tissue was stained with hematoxylin-eosin for the observation of morphological changes. The mRNA levels of microtubule-associated protein 1 light chain 3 beta(LC3B), Beclin1, p62, HIF-1α, and HO-1 in the myocardial tissue were determined by RT-qPCR. The protein levels of LC3B, beclin1, p62, autophagy-related protein 5(ATG5), HIF-1α, and HO-1 were determined by Western blot. The results showed that 103 active components of LGZGD, corresponding to 224 targets, were obtained. A total of 3 485 and 6 165 targets related to MI and CHF, respectively, were retrieved. The GSE16499 dataset obtained 3 263 differentially expressed genes. There were 31 common targets. The top 3 core active components were quercetin, naringenin, and 1-methoxyphaseollidin. The topology analysis results showed that the core targets were MAPK3, HMOX1(HO-1), MYC, ADRB2, PPARD, and HIF1A(HIF-1α). The molecular docking results showed strong binding between the core targets and the main active components of LGZGD. LGZGD significantly improved the heart function and alleviated the pathological changes in the myocardial tissue of mice. Western blot and RT-qPCR results showed that the HIF-1α/HO-1 signaling pathway and autophagy were activated in the model group. LGZGD up-regulated the levels of LC3B, Beclin1, ATG5, HIF-1α, and HO-1 while down-regulating the mRNA and protein levels of p62. In summary, LGZGD can enhance autophagy and improve the heart function in the mouse model of CHF after MI by upregulating the HIF-1α/HO-1 signaling pathway.
Animals ; Drugs, Chinese Herbal/chemistry* ; Myocardial Infarction/drug therapy* ; Heart Failure/physiopathology* ; Mice ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Signal Transduction/drug effects* ; Male ; Computational Biology ; Heme Oxygenase-1/genetics* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Mice, Inbred C57BL ; Humans ; Chronic Disease ; Disease Models, Animal

BACKGROUND: Approximately 70% patients with acute myocardial infarction (AMI) presented without ST-segment elevation on electrocardiogram. Patients with non-ST segment elevation myocardial infarction (NSTEMI) often presented with atypical symptoms, which may be related to pre-hospital delay and increased risk of mortality. However, up to date few studies reported detailed symptomatology of NSTEMI, particularly among Asian patients. The objective of this study was to describe and compare symptoms and presenting characteristics of NSTEMI vs. STEMI patients. METHODS: We enrolled 21,994 patients diagnosed with AMI from China Acute Myocardial Infarction (CAMI) Registry between January 2013 and September 2014. Patients were divided into 2 groups according to ST-segment elevation: ST-segment elevation (STEMI) group and NSTEMI group. We extracted data on patients' characteristics and detailed symptomatology and compared these variables between two groups. RESULTS: Compared with patients with STEMI (N = 16,315), those with NSTEMI (N = 5679) were older, more often females and more often have comorbidities. Patients with NSTEMI were less likely to present with persistent chest pain (54.3% vs. 71.4%), diaphoresis (48.6% vs. 70.0%), radiation pain (26.4% vs. 33.8%), and more likely to have chest distress (42.4% vs. 38.3%) than STEMI patients (all P < 0.0001). Patients with NSTEMI were also had longer time to hospital. In multivariable analysis, NSTEMI was independent predictor of presentation without chest pain (odds ratio: 1.974, 95% confidence interval: 1.849-2.107). CONCLUSIONS: Patients with NSTEMI were more likely to present with chest distress and pre-hospital patient delay compared with patients with STEMI. It is necessary for both clinicians and patients to learn more about atypical symptoms of NSTEMI in order to rapidly recognize myocardial infarction. TRIAL REGISTRATION www.clinicaltrials.gov (No. NCT01874691).
Aged ; Arrhythmias, Cardiac ; pathology ; physiopathology ; China ; Electrocardiography ; methods ; Female ; Hospital Mortality ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; pathology ; physiopathology ; Odds Ratio ; Registries ; Risk Factors ; ST Elevation Myocardial Infarction ; pathology ; physiopathology

We described two patients who were successfully resuscitated from out-of-hospital cardiac arrest. Their ECGs showed ST elevations in V1 and aVR, as well as diffuse ST depression. Their ST elevation in V1 was noted to be greater than in aVR. While one patient was found to have an occlusion of the right ventricular (RV) branch of the right coronary artery, the other was found to have an occlusion of a proximal non-dominant right coronary artery supplying the RV branch. Successful primary percutaneous coronary intervention was performed for each patient with angioplasty and implantation of a drug-eluting stent. Both patients made good physical and neurological recovery.
Adult ; Angioplasty ; Angioplasty, Balloon, Coronary ; Cardiopulmonary Resuscitation ; Coronary Vessels ; physiopathology ; Defibrillators ; Drug-Eluting Stents ; Electrocardiography ; Heart Ventricles ; physiopathology ; Hepatitis B ; complications ; Humans ; Male ; Myocardial Infarction ; diagnosis ; physiopathology ; Out-of-Hospital Cardiac Arrest ; therapy ; Percutaneous Coronary Intervention ; Resuscitation ; Singapore