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Objective: To determine the effect of electroacupuncture (EA) on β1-adrenergic receptor (β1-AR) and post-receptor protein kinase A (PKA) signaling pathway after acute myocardial ischemia (MI). Methods: An MI model was established by ligating the left anterior descending coronary artery of wild-type (WT) C57/BL and β1-AR+/– mice (heterozygous for β1-AR gene deletion). EA treatment was administered at HT5-HT7 or LU9-LU8. We evaluated cardiac function by measuring ST segment displacement, ischemic area and serum levels of creatine kinase (CK)-MB and lactate dehydrogenase (LDH). Pathological morphology/apoptosis of myocardial tissue were examined using hematoxylin–eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Norepinephrine (NE) levels in myocardial tissue were detected by ELISA. Levels of β1 and post-receptor PKA signaling components were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Results: EA stimulation at HT7-HT5 could better regulate the level of β1-AR in myocardial tissue than that at LU9-LU8. Following EA, the ST segment, serum CK-MB/ LDH and area of myocardial infarction were decreased in WT mice, and the degree of myocardial pathology/apoptosis and expression of cleaved caspase-3 were decreased. Myocardial levels of Gs protein (Gs), adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), phosphorylated protein kinase A (p-PKA), L-type voltage-gated calcium channel α1C (Cav1.2), serine phosphate 16-phospholamban (p-PLBs16) and sarcoplasmic reticulum Ca2+-adenosine triphosphate (ATP)ase 2a (SERCA2a) increased after EA. However, these effects of EA were not replicated in β1-AR+/– mice. Interestingly, myocardial NE content decreased after EA in WT and β1-AR+/– mice. Conclusion: EA may enhance cardiac function and reduced MI area/apoptosis by restoring the activity of β1-AR and post-receptor PKA signaling. [ABSTRACT FROM AUTHOR]

• Patients with acute coronary syndromes (ACS) without classic symptoms of chest pain may delay seeking medical care. • Acute ischemic changes were visible on a smartwatch single-lead electrocardiogram within minutes of symptoms onset. • Alerts from widely available wearable devices of possible ACS may prompt patients to seek immediate medical evaluation. [ABSTRACT FROM AUTHOR]

Persicae Semen is an edible Chinese herbal medicine that ameliorates myocardial ischemia. However, its pharmacodynamic properties and mechanisms of action remain unclear. This study aimed to investigate the ameliorative effect of Persicae Semen extract (PS) on acute myocardial ischemia (AMI) in rats and explore its mechanism of action. After the PS administration to rats, 12 compounds were identified in the plasma. PS can significantly improve cardiac function, regulate creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin (cTn I), α-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels in the serum, and ameliorate the pathological injury of AMI in rats. Metabolomics and network pharmacology of components absorbed in to plasma showed that PS may regulate the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism, then ameliorate myocardial ischemic injury. This study found that PS significantly improved cardiac function in rats with AMI, through the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism.

Background: The Danshen-Honghua herb pair (DHHP) is a common modern Chinese medicine pair for activating blood circulation and resolving blood stasis. It has been used for centuries to treat cardiovascular and cerebrovascular diseases and is often found in some herbal compounds for treating cardiovascular diseases. The aim of this study was to explore the effects of DHHP on the intestinal flora of rats with acute myocardial ischemia and its microbial transformation in vitro. Methods: In this study, we investigated the protective effect of DHHP on isoproterenol-induced acute myocardial ischemia in rats based on metagenomic sequencing technology, and further characterized the in vitro metabolic transformation products of DHHP, so as to investigate its anti-myocardial ischemic efficacy material basis. Results: Pharmacodynamic results demonstrated that DHHP significantly ameliorated pathological changes and improved abnormal cardiac enzyme levels in acute myocardial ischemia rats. In addition, metagenomic analysis showed the efficacy of DHHP in ameliorating the isoproterenol-induced modifications of the intestinal flora in rats. Specifically, DHHP promoted the growth of the intestinal potential probiotics such as Lactobacillus while suppressing the pathogenic bacteria, including Escherichia and Streptococcus. The in vitro metabolism results showed that the DHHP's active components underwent primarily phase I metabolism through hydroxylation, decarboxylation, and dehydration inversions in the isolated intestinal flora of acute myocardial ischemia rats and in phase II through sulfation esterification and methylation reactions. Conclusion: The results suggest that there may be a bidirectional regulatory effect between DHHP and intestinal flora, which is important to explain the pharmacological mechanism of DHHP. [ABSTRACT FROM AUTHOR]

Background: To explore the effect of electroacupuncture Wushu acupoints on angiogenesis and expressions of brain-derived neurotrophic factor (BDNF), as well as to explore the possible mechanism of electroacupuncture on acute myocardial ischemia (AMI). Methods: We randomly divided 42 Sprague Dawley rats into sham AMI group, AMI group, and the heart channel groups comprising Shaochong (HT9) acupoint, Shaofu (HT8) acupoint, Shenmen (HT7) acupoint, Lingdao (HT4) acupoint, and Shaohai (HT3) acupoint groups, with 6 rats in each group. The AMI model was fabricated via hypodesmus of the left anterior descending coronary artery. After modeling, the corresponding acupoints of each group underwent electroacupuncture treatment 30 min/time, once/day for 3 consecutive days. The cardiogram obtained before and after the intervention was compared, and the pathologic changes of the myocardial tissue were observed via hematoxylin & eosin staining. The amount of serum endothelin-1, prostacycline-2, thromboxane-2, and BDNF indicators were assayed using ELISA, the number of CD31-positive cells in myocardial tissue was calculated using immunohistochemistry, and the expression levels of BDNF and TrKB was measured using western blot. Result: Compared with the sham AMI group, the ST segment on the electrocardiogram was significantly elevated (P < 0.05); the myocardial angiogenesis marker CD31 was remarkably increased (P < 0.05); serum levels of endothelin-1, prostacycline-2 and prostacycline-2/thromboxane-2 were decreased (P < 0.05), whereas serum levels of thromboxane-2 levels were increased (P < 0.05); and those of serum BDNF was decreased (P < 0.05); the protein overexpression contents of BDNF and TrKB in the myocardial tissues of HT8 acpoint and Shenmen acpoint groups were reduced (P < 0.05) in the AMI group. Compared with the AMI group, in the heart channel groups, the ST segment of electrocardiogram was dramatically reduced (P < 0.05); CD31 was dramatically elevated (P < 0.05); the serum levels of endothelin-1, prostacycline-2, and prostacycline-2/thromboxane-2 were increased (P < 0.05), thromboxane-2 levels were reduced (P < 0.05); the serum BDNF level was increased (P < 0.05); the protein overexpression levels of BDNF and TrKB in myocardial tissue of HT8 group and Shenmen group was increased (P < 0.05). Conclusion: electroacupuncture of Wushu acupoints along the heart channel may enhance myocardial ischemia by promoting overexpression of serum BDNF and activating the BDNF/TrKB pathway to promote myocardial angiogenesis. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmia (VT/VF) can complicate acute myocardial ischemia (AMI). Regional instability of repolarization during AMI contributes to the substrate for VT/VF. Beat-to-beat variability of repolarization (BVR), a measure of repolarization lability increases during AMI. We hypothesized that its surge precedes VT/VF. We studied the spatial and temporal changes in BVR in relation to VT/VF during AMI. In 24 pigs, BVR was quantified on 12-lead electrocardiogram recorded at a sampling rate of 1 kHz. AMI was induced in 16 pigs by percutaneous coronary artery occlusion (MI), whereas 8 underwent sham operation (sham). Changes in BVR were assessed at 5 min after occlusion, 5 and 1 min pre-VF in animals that developed VF, and matched time points in pigs without VF. Serum troponin and ST deviation were measured. After 1 mo, magnetic resonance imaging and VT induction by programmed electrical stimulation were performed. During AMI, BVR increased significantly in inferior-lateral leads correlating with ST deviation and troponin increase. BVR was maximal 1 min pre-VF (3.78 ± 1.36 vs. 5 min pre-VF, 1.67 ± 1.56, P < 0.0001). After 1 mo, BVR was higher in MI than in sham and correlated with the infarct size (1.43 ± 0.50 vs. 0.57 ± 0.30, P = 0.009). VT was inducible in all MI animals and the ease of induction correlated with BVR. BVR increased during AMI and temporal BVR changes predicted imminent VT/VF, supporting a possible role in monitoring and early warning systems. BVR correlated to arrhythmia vulnerability suggesting utility in risk stratification post-AMI. NEW & NOTEWORTHY The key finding of this study is that BVR increases during AMI and surges before ventricular arrhythmia onset. This suggests that monitoring BVR may be useful for monitoring the risk of VF during and after AMI in the coronary care unit settings. Beyond this, monitoring BVR may have value in cardiac implantable devices or wearables. Ventricular arrhythmia (VT/VF) can complicate acute myocardial ischemia (AMI). Regional instability of repolarization during AMI contributes to the substrate for VT/VF. Beat-to-beat variability of repolarization (BVR), a measure of repolarization lability increases during AMI. We hypothesized that its surge precedes VT/VF. We studied the spatial and temporal changes in BVR in relation to VT/VF during AMI. In 24 pigs, BVR was quantified on 12-lead electrocardiogram recorded at a sampling rate of 1 kHz. AMI was induced in 16 pigs by percutaneous coronary artery occlusion (MI), whereas 8 underwent sham operation (sham). Changes in BVR were assessed at 5 min after occlusion, 5 and 1 min pre-VF in animals that developed VF, and matched time points in pigs without VF. Serum troponin and ST deviation were measured. After 1 mo, magnetic resonance imaging and VT induction by programmed electrical stimulation were performed. During AMI, BVR increased significantly in inferior-lateral leads correlating with ST deviation and troponin increase. BVR was maximal 1 min pre-VF (3.78 ± 1.36 vs. 5 min pre-VF, 1.67 ± 1.56, P < 0.0001). After 1 mo, BVR was higher in MI than in sham and correlated with the infarct size (1.43 ± 0.50 vs. 0.57 ± 0.30, P = 0.009). VT was inducible in all MI animals and the ease of induction correlated with BVR. BVR increased during AMI and temporal BVR changes predicted imminent VT/VF, supporting a possible role in monitoring and early warning systems. BVR correlated to arrhythmia vulnerability suggesting utility in risk stratification post-AMI. NEW & NOTEWORTHY The key finding of this study is that BVR increases during AMI and surges before ventricular arrhythmia onset. This suggests that monitoring BVR may be useful for monitoring the risk of VF during and after AMI in the coronary care unit settings. Beyond this, monitoring BVR may have value in cardiac implantable devices or wearables. [ABSTRACT FROM AUTHOR]

Abstract Background Red ginseng (RG) was widely used as traditional Chinese medicine (TCM) or dietary supplement. However, few researches had been reported on the red ginseng polysaccharide (RGP). Methods In this study, a novel heteropolysaccharide named RGP1-1 was fractionated sequentially by DEAE-52 column and Sephadex G-100 gel column. The primary structure of RGP1-1, including glycosyl linkages, molecular weight, monosaccharide composition, morphology and physicochemical property were conducted by nuclear magnetic resonance (NMR), gas chromatography-mass spectrometer (GC–MS), atomic force microscope (AFM), scanning electron microscope (SEM), differential scanning calorimetry-thermogravimetric analysis (DSC-TG) and so on. The effect of RGP1-1 in preventing and treating myocardial ischemia was evaluated by an animal model isoprenaline (ISO) induced mice. Results RGP1-1, with a homogeneous molecular weight of 5655 Da, was composed of Glc and Gal in the ratio of 94.26:4.92. The methylation and NMR analysis indicated the backbone was composed of → 1)-Glcp-(4 → and → 1)-Galp-(4 →, branched partially at O-4 with α-D-Glcp-(1 → residue. Morphology and physicochemical property analysis revealed a triple-helical conformation, flaky and irregular spherical structure with molecule aggregations and stable thermal properties of RGP1-1. And it contained 6.82 mV zeta potential, 117.4 nm partical size and polymerization phenomenon. Furthermore, RGP1-1 possessed strong antioxidant activity in vitro and in vivo, RGP1-1 could decrease cardiomyocyte apoptosis and myocardium fibrosis of mice in histopathology and it could decrease significantly the serum levels of cardiac troponin (cTnI), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA). Western blot analysis showed that RGP1-1 can increase the expression of main protein Nuclear factor E2-related factor 2(Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1(HO-1) and kelch-like ECH-associated protein1(keap1) in oxidative stress injure progress, and therefore regulate the pathway of Nrf2/HO-1. Conclusion The above findings indicated that RGP1-1 had an improving effect on ISO-induced myocardial ischemia injury in mice, as novel natural antioxidant and heart-protecting drugs.

Yanqin Li,1,&ast; Xiaoqian Sun,1,&ast; Xiangning Liu,1,&ast; Junjun Li,2 Xuan Li,1 Gang Wang,1 Yizhou Liu,1 Xiangyu Lu,2 Lingwen Cui,2 Mingyan Shao,3 Yong Wang,1,3,4 Wei Wang,1,4,5 Chun Li2,4 1College of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2Modern Research Center for Traditional Chinese Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Beijing Key Laboratory of TCM Syndrome and Formula, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 5Guangzhou University of Chinese Medicine, Guangdong, 510006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wang, Guangzhou University of Chinese Medicine, Guangdong, 510006, People’s Republic of China, Tel +86 13910026960, Email wangwei26960@126.com Chun Li, Modern Research Center for Traditional Chinese Medicine, School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China, Tel +86 15810068615, Email lichun19850204@163.comBackground: Acute myocardial ischemia (AMI) is a common heart disease with increasing morbidity and mortality year by year. Persistent and sterile inflammatory infiltration of myocardial tissue is an important factor triggering of acute myocardial ischemia secondary to acute myocardial infarction, and NLRP3 inflammasome activation is an important part of sterile inflammatory response after acute myocardial ischemia. Previous studies have shown that Qishen granule (QSG) can significantly inhibit the inflammatory injury of myocardial tissue caused by ischemia, but its effect and specific mechanism of inhibiting the activation of NLRP3 inflammasome have not been reported. This study was to investigate the specific mechanism of QSG inhibiting inflammation after AMI, and to validate the possible targets.Methods: The myocardial ischemia model in mice was established by ligation of the left anterior descending coronary artery. Echocardiography was used to evaluate the cardiac function of the mice. Plasma CK-MB and cTnl were detected by ELISA to evaluate the degree of myocardial injury. The extent of myocardial tissue inflammation in mice was assessed by HE staining and immunohistochemistry of IL-18, IL-1β. The expressions of NLRP3, ASC, Caspase-1, and CD86 were detected by immunofluorescence; detection of key pathway proteins P2X7R, NEK7, NLRP3, ASC, Caspase-1, and effector proteins IL-18, IL-1β by Western blot. In vitro experiments, ATP+LPS was used to construct a RAW264.7 macrophage NLRP3 inflammasome activation model. Immunofluorescence and Western blot analysis were performed to detect the expression of NLRP3 pathway activator and effector proteins. Plasmid-transfected P2X7R overexpression and immunoprecipitation assays were used to evaluate the QSG-regulated NLRP3 inflammasome activation pathway.Results: QSG rescued cardiac function and further reduced inflammatory effects in mice by inhibiting NLRP3 inflammasome activation. In vitro, QSG inhibited LPS combined with ATP-induced NLRP3 inflammasome activation in RAW264.7 macrophages by downregulating the expression of NLRP3 inflammasome key pathway proteins. In addition, inhibition or overexpression of P2X7R in RAW264.7 macrophages and immunoprecipitated protein interactions further confirmed that QSG reduces macrophages inflammasome activation via the P2X7R-NEK7-NLRP3 pathway.Conclusion: P2X7R-NEK7-NLRP3 inflammasome activation is a novel therapeutic mechanism of QSG in the treatment of acute myocardial ischemia.Keywords: acute myocardial ischemia, inflammation, macrophages, P2X7R-NEK7, NLRP3 inflammasome, Qishen granule

Coronavirus disease 2019 (COVID‐19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has been shown that SARS‐CoV‐2 infection‐induced inflammatory and oxidative stress and associated endothelial dysfunction may lead to the development of acute coronary syndrome (ACS). Therefore, this review aimed to ascertain the link between severe SARS‐CoV‐2 infection and ACS. ACS is a spectrum of acute myocardial ischemia due to a sudden decrease in coronary blood flow, ranging from unstable angina to myocardial infarction (MI). Primary or type 1 MI (T1MI) is mainly caused by coronary plaque rupture and/or erosion with subsequent occlusive thrombosis. Secondary or type 2 MI (T2MI) is due to cardiac and systemic disorders without acute coronary atherothrombotic disruption. Acute SARS‐CoV‐2 infection is linked with the development of nonobstructive coronary disorders such as coronary vasospasm, dilated cardiomyopathy, myocardial fibrosis, and myocarditis. Furthermore, SARS‐CoV‐2 infection is associated with systemic inflammation that might affect coronary atherosclerotic plaque stability through augmentation of cardiac preload and afterload. Nevertheless, major coronary vessels with atherosclerotic plaques develop minor inflammation during COVID‐19 since coronary arteries are not initially and primarily targeted by SARS‐CoV‐2 due to low expression of angiotensin‐converting enzyme 2 in coronary vessels. In conclusion, SARS‐CoV‐2 infection through hypercytokinemia, direct cardiomyocyte injury, and dysregulation of the renin‐angiotensin system may aggravate underlying ACS or cause new‐onset T2MI. As well, arrhythmias induced by anti‐COVID‐19 medications could worsen underlying ACS. [ABSTRACT FROM AUTHOR]

BACKGROUND: With the increasing prevalence and mortality of ischemic heart disease, it is very important to study the pathophysiological mechanism, diagnosis and treatment of myocardial ischemia. By constructing animal models, researchers can deeply understand the pathophysiological mechanisms, therapeutic effects and drug safety of myocardial ischemia. OBJECTIVE: To summarize myocardial ischemia model methods so as to reveal the present situation and progress of myocardial ischemia animal models and to compare the advantages and disadvantages of various establishing methods, thereby providing reference for relevant clinical studies. METHODS: The databases of CNKI, WanFang Data Knowledge Service Platform, PubMed and GeenMedical were searched by computer from January 2000 to December 2021 using the keywords of “myocardial ischemia; animal models; miniature pigs.” Finally, 52 articles were included for review analysis according to inclusion and exclusion criteria. RESULTS AND CONCLUSION: At present, the clinical models of myocardial ischemia mainly include large animal species (dogs and pigs), rabbits, and rodents (rats and mice). Miniature pigs are the most ideal animal model donors for ischemic heart disease and have been widely used to prepare myocardial ischemia models. Among various methods for establishing acute myocardial ischemia models, open heart surgery and microcurrent stimulation have the characteristics of accurate positioning. Compared with the open thoracic surgery, closed thoracic surgery, drugs and microcurrent stimulation are simpler and more suitable for the clinical pathological process of acute myocardial ischemia. Moreover, the closed thoracic surgery that is minimally invasive and of high repeatability has become the preferred method. The main methods to construct the model of chronic myocardial ischemia include intima proliferation method, external chronic contraction method, microcirculation embolization method, high-fat diet method and subtotal ligation method. Microcirculation embolization can be used to explore the pathological mechanism of chronic myocardial ischemia caused by microcirculation disorders by blocking microvessels. In principle, both chronic extravascular contraction and subtotal ligation lead to chronic myocardial ischemia through extravascular mechanical compression, but subtotal ligation has a more controllable stenosis range and less damage to the natural structure of the vascular wall than chronic contraction. Intimal proliferation combined with high-fat diet is the most commonly used method to construct chronic myocardial ischemia model, as this combined method is closer to the clinical pathological mechanism of chronic coronary artery stenosis caused by atherosclerotic plaque. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiac damage is common in patients with acute brain injury; however, little is known regarding cardiac-induced neurological symptoms. In the International Classification of Headache, Third Edition (ICHD-III), cardiac cephalalgia is classified as a headache caused by impaired homeostasis. Methods This report presents four patients with acute myocardial infarction (AMI) who presented with headache that fulfilled the ICHD-III diagnostic criteria for cardiac cephalalgia. A systematic review of cardiac cephalalgia using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines is also presented. Results Case 1: A 69-year-old man with a history of percutaneous coronary intervention (PCI) developed sudden severe occipital pain, nausea, and cold sweating. Coronary angiography (CAG) revealed occlusion of the right coronary artery (RCA). Case 2: A 66-year-old woman complained of increasing occipitalgia and chest discomfort while riding a bicycle. CAG demonstrated 99% stenosis of the left anterior descending artery. Case 3: A 54-year-old man presented with faintness, cold sweating, and occipitalgia after eating lunch. CAG detected occlusion of the RCA. Case 4: A 72-year-old man went into shock after complaining of a sudden severe headache and nausea. Vasopressors were initiated and emergency CAG was performed, which detected three-vessel disease. In all four, electrocardiography (ECG) showed ST segment elevation or depression and echocardiography revealed a left ventricular wall motion abnormality. All patients underwent PCI, which resulted in headache resolution after successful coronary reperfusion. A total of 59 cases of cardiac cephalalgia were reviewed, including the four reported here. Although the typical manifestation of cardiac cephalalgia is migraine-like pain on exertion, it may present with thunderclap headache without a trigger or chest symptoms, mimicking subarachnoid hemorrhage. ECG may not always show an abnormality. Headaches resolve after successful coronary reperfusion. Conclusions Cardiac cephalalgia resulting from AMI can present with or without chest discomfort and even mimic the classic thunderclap headache associated with SAH. It should be recognized as a neurological emergency and treated without delay.

The investigation purpose was to study the effect of fabomotizole on blood microcirculation in intact and ischemic myocardium in conditions of acute ischemia of the heart muscle. The experiments were carried out on anesthetized (urethane, 1300 mg/kg, i.p.) white mongrel male rats weighing 220–250 g. Acute myocardial ischemia was caused by occlusion of the left coronary artery. Blood microcirculation was evaluated by laser Doppler flowmetry using a computerized laser analyzer "LAKK-OP2". It was found that fabomotizole (15 mg/kg, i.v.) in an intact heart does not affect blood microcirculation. Immediately after coronary artery ligation in the myocardial ischemia zone, microcirculation decreases sharply (by about 30 %, p = 0.0106) and practically does not change in the conditionally intact myocardium. Fabomotizole, administered 5 minutes before occlusion of the coronary artery, prevented a decrease in microcirculation in the ischemiс zone of the myocardium. The ability of fabomotizole in conditions of acute myocardial ischemia to prevent a decrease in the level of microcirculation in the ischemic zone may contribute to the anti-ischemic activity of the drug.

• The postmortem diagnosis of acute myocardial ischemia is challenging. • Immunohistochemical and gene expression studies are promising fields. • HIF-1α may represent an appropriate biomarker of acute myocardial infarction. • mRNA-210 may represent a useful biomarker of acute myocardial infarction. The postmortem diagnosis of acute myocardial ischemia (AMI) represents a challenging issue in forensic practice. Immunohistochemical studies and gene expression studies are becoming a promising field of research in forensic pathology. The present study aims to evaluate HIF-1α expression through immunohistochemistry (IHC), and mRNA-210 level using real-time polymerase chain reaction (RT-PCR), in order to define if HIF-1α and mRNA-210 in post-mortem myocardium could be adopted in the diagnosis of AMI. Thirty-five deceased individuals, who underwent forensic autopsy at the Legal Medicine Service of the University of Parma, between 2010 and 2018, were investigated. The cohort was divided into two groups according to the cause of death (sudden deaths caused by AMI vs control cases). Cardiac specimens were collected during autopsy, then samples were processed for morphological evaluation using haematoxylin–eosin staining, for IHC, and for RT-PCR. HIF-1α expression and mRNA-210 levels were investigated. Statistical evaluation demonstrated statistically significant differences in terms of number of IHC positive vessels, leukocytes, and cardiomyocytes between the two groups. Moreover, in the majority of cases, immunostaining positivity was observed only in myocardial and subendocardial samples. With reference to mRNA-210, the difference between the two groups proved to be statistically significant. The present study indicates that HIF-1α and mRNA-210 in post-mortem cardiac specimens could represent appropriate biomarkers in the diagnosis of AMI. The current study was primarily limited by the scarcity of the cohort, so further research is required to confirm these preliminary observations. [ABSTRACT FROM AUTHOR]

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

Allium fistulosum (Welsh onion) is a perennial onion species that originates in eastern Asia. It is an important cooking ingredient in eastern countries, such as China, Japan, and Korea. In western countries, it is primarily used as a scallion or salad onion. According to the dictionary of Chinese drugs, the seeds of A. fistulosum, a traditional Chinese medicine, are used as tonic and aphrodisiac. The purpose of this study was to evaluate the protective effect of the seeds of A. fistulosum extract (SAFE) against acute myocardial ischemia. Rat and dog acute myocardial ischemia models were used, the model of acute myocardial ischemia in rats were divided into six groups: control group (saline, 10 mL·kg−1), model group (saline, 10 mL·kg−1), SAFE low, medium and high dose groups（50, 150, 300 mg·kg−1）and the positive control group (Xingling granule, 900 mg·kg−1), and the model of acute myocardial ischemia in dogs were also divided into the control group （saline, 2 mL·kg−1）, SAFE low, medium and high dose groups（15, 45, 90 mg·kg−1）and the positive control group (Xingling granule, 300 mg·kg−1). Myocardial ischemia degree was measured by epicardium electrocardiogram, the range of myocardial infarction was determined by quantitative histology （N-BT staining), and serum creatine kinase (CK）and lactate dehydrogenase（LDH) content were detected by biochemical assay. Compared with the control group, the results showed that SAFE could reduce the degree of myocardial ischemia, infarcted area, and elevation of serum CK and LDH levels in rats and dogs after coronary ligation. In conclusion, SAFE can improve acute myocardial ischemia and reduce myocardial infarction in rats and dogs, and which suggests that it can achieve prevention effects of myocardial ischemia.

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is one of the major leading causes of death in humans globally. Recently, increased levels of recruited macrophages and AGE-albumin were observed in the hearts of humans and animals with acute myocardial infarction. Thus, the purposes of this study were to investigate whether the elevated levels of AGE-albumin from activated macrophage cells are implicated in ischemia-induced cardiomyocyte death and to develop therapeutic strategies for AMI based on its underlying molecular mechanisms with respect to AGEs. The present study demonstrated that activated macrophages and AGE-albumin were observed in heart tissues obtained from humans and rats with AMI incidences. In the cellular model of AMI, it was found that increased expression of AGE-albumin was shown to be co-localized with macrophages, and the presence of AGE-albumin led to increased expression of RAGE through the mitogen-activated protein kinase pathway. After revealing cardiomyocyte apoptosis induced by toxicity of the AGE-RAGE system, sRAGE-secreting MSCs were generated using the CRISPR/Cas9 platform to investigate the therapeutic effects of sRAGE-MSCs in an AMI rat model. Gene-edited sRAGE-MSCs showed greater therapeutic effects against AMI pathogenesis in rat models compared to mock MSCs, and promising results of the functional improvement of stem cells could result in significant improvements in the clinical management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of electroacupuncture (EA) on β 1 -adrenergic receptor (β 1 -AR) and post-receptor protein kinase A (PKA) signaling pathway after acute myocardial ischemia (MI)., Methods: An MI model was established by ligating the left anterior descending coronary artery of wild-type (WT) C57/BL and β 1 -AR +/- mice (heterozygous for β 1 -AR gene deletion). EA treatment was administered at HT5-HT7 or LU9-LU8. We evaluated cardiac function by measuring ST segment displacement, ischemic area and serum levels of creatine kinase (CK)-MB and lactate dehydrogenase (LDH). Pathological morphology/apoptosis of myocardial tissue were examined using hematoxylin-eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Norepinephrine (NE) levels in myocardial tissue were detected by ELISA. Levels of β 1 and post-receptor PKA signaling components were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting., Results: EA stimulation at HT7-HT5 could better regulate the level of β 1 -AR in myocardial tissue than that at LU9-LU8. Following EA, the ST segment, serum CK-MB/ LDH and area of myocardial infarction were decreased in WT mice, and the degree of myocardial pathology/apoptosis and expression of cleaved caspase-3 were decreased. Myocardial levels of Gs protein (Gs), adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), phosphorylated protein kinase A (p-PKA), L-type voltage-gated calcium channel α1C (Cav1.2), serine phosphate 16-phospholamban (p-PLB s16 ) and sarcoplasmic reticulum Ca 2+ -adenosine triphosphate (ATP)ase 2a (SERCA2a) increased after EA. However, these effects of EA were not replicated in β 1 -AR +/- mice. Interestingly, myocardial NE content decreased after EA in WT and β 1 -AR +/- mice., Conclusion: EA may enhance cardiac function and reduced MI area/apoptosis by restoring the activity of β 1 -AR and post-receptor PKA signaling., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Red ginseng (RG) was widely used as traditional Chinese medicine (TCM) or dietary supplement. However, few researches had been reported on the red ginseng polysaccharide (RGP). Methods: In this study, a novel heteropolysaccharide named RGP1-1 was fractionated sequentially by DEAE-52 column and Sephadex G-100 gel column. The primary structure of RGP1-1, including glycosyl linkages, molecular weight, monosaccharide composition, morphology and physicochemical property were conducted by nuclear magnetic resonance (NMR), gas chromatography-mass spectrometer (GC–MS), atomic force microscope (AFM), scanning electron microscope (SEM), differential scanning calorimetry-thermogravimetric analysis (DSC-TG) and so on. The effect of RGP1-1 in preventing and treating myocardial ischemia was evaluated by an animal model isoprenaline (ISO) induced mice. Results: RGP1-1, with a homogeneous molecular weight of 5655 Da, was composed of Glc and Gal in the ratio of 94.26:4.92. The methylation and NMR analysis indicated the backbone was composed of → 1)-Glcp-(4 → and → 1)-Galp-(4 →, branched partially at O-4 with α-D-Glcp-(1 → residue. Morphology and physicochemical property analysis revealed a triple-helical conformation, flaky and irregular spherical structure with molecule aggregations and stable thermal properties of RGP1-1. And it contained 6.82 mV zeta potential, 117.4 nm partical size and polymerization phenomenon. Furthermore, RGP1-1 possessed strong antioxidant activity in vitro and in vivo, RGP1-1 could decrease cardiomyocyte apoptosis and myocardium fibrosis of mice in histopathology and it could decrease significantly the serum levels of cardiac troponin (cTnI), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malondialdehyde (MDA). Western blot analysis showed that RGP1-1 can increase the expression of main protein Nuclear factor E2-related factor 2(Nrf2), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase-1(HO-1) and kelch-like ECH-associated protein1(keap1) in oxidative stress injure progress, and therefore regulate the pathway of Nrf2/HO-1. Conclusion: The above findings indicated that RGP1-1 had an improving effect on ISO-induced myocardial ischemia injury in mice, as novel natural antioxidant and heart-protecting drugs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical characteristics of cardiac cephalalgia and determine whether there is a more suitable alternative criterion. Method: Patients with cardiac cephalalgia diagnosed and treated from May 2019 to April 2021 in the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) were prospectively and consecutively collected, their clinical manifestations were analyzed, and compared with the 2018 diagnostic criteria. Results: A total of 30 patients were collected, including 16 males and 14 females. The onset age ranged from 31 to 84 years old, with a mean of 64.6 ± 11.9 years. Headache was more common in unilateral or bilateral frontotemporal, and the nature of pain includes pulsating, dull, stuffy pain, throbbing and so on. 80.0% were moderate to severe, 70% lasted less than half an hour, 76.6% had chest pain, 70% had chest tightness, 63.3% had sweating, and 36.6% had nausea. After treatment with drugs or coronary angiogenesis, except for one death, headache was fully or partially relieved in 29 patients. Conclusion: Cardiac cephalalgia is generally located in frontotemporal region, of moderate or severe intensity, with a pulsating or throbbing sensation, abating within 30 minutes, and has a good prognosis. Accompanying chest pain, chest tightness, and sweating should be included in the diagnostic criteria. [ABSTRACT FROM AUTHOR]

BackgroundLeonurus japonicus Houtt has an obvious efficacy on cardiovascular diseases. As the most representative component in the herb, leonurine has attracted increasing attention for its potential in myocardial ischemia. However, its protective mechanism against myocardial ischemia remains incompletely elucidated.ObjectivesThe present study aimed to reveal the potential mechanism of leonurine in acute myocardial ischemia using a strategy combining metabolomics and network pharmacology.MethodsFirst, a metabolomics method was proposed to identify the differential metabolites of plasma in rats. Then, network pharmacology was performed to screen candidate targets of leonurine against acute myocardial ischemia. A compound-reaction-enzyme-gene network was thus constructed with the differential metabolites and targets. Finally, molecular docking was carried out to predict the binding capability of leonurine with key targets.ResultsA total of 32 differential metabolites were identified in rat plasma, and 16 hub genes were detected through network pharmacology. According to the results of compound-reaction-enzyme-gene network and molecular docking, what was screened included six key targets (GSR, CYP2C9, BCHE, GSTP1, TGM2, and PLA2G2A) and seven differential metabolites (glycerylphosphorylcholine, lysophosphatidylcholine, choline phosphate, linoleic acid, 13-HpODE, tryptophan and glutamate) with four important metabolic pathways involved: glycerophospholopid metabolism, linoleic acid metabolism, tryptophan metabolism and glutamate metabolism. Among them, glycerophospholipid and tryptophan metabolism were shown to be important, since the regulation of leonurine on these two pathways was also observed in our previous metabolomics study conducted on clinical hyperlipidemia patients.ConclusionThis is the first study of its kind to reveal the underlying mechanism of leonurine against acute myocardial ischemia through a strategy combining metabolomics and network pharmacology, which provides a valuable reference for the research on its future application.

Objectives This feasibility study was conducted to inform the design and power evaluation of CODE-MI, a pan-Canadian trial evaluating the impact of using the female-specific 99th-percentile threshold for high-sensitivity cardiac troponin (hs-cTn) on the diagnosis, treatment and outcomes of women presenting to the emergency department with symptoms suggestive for myocardial ischemia. Approach CODE-MI is a multi-center, stepped-wedge cluster randomized trial. The cohort and outcomes will be obtained from routinely collected administrative data. Using linked administrative data from 11 hospitals in Ontario from 2014/10 to 2017/09, this feasibility study obtained the following estimates: number of eligible patients, i.e., women presenting to the emergency department with symptoms suggestive of myocardial ischemia and a 24-hour peak hs-cTn value within the female-specific and overall thresholds (i.e. primary cohort); the rate of the 1-year composite outcome of all-cause mortality, re-admission for non-fatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization. Study power was evaluated via simulations. Results Overall, 2,073,849 emergency department visits were assessed. Among women, chest pain (with or without cardiac features) and shortness of breath were the most common complaints associated with a diagnosis of acute coronary syndrome. An estimated 7.7% of women with these complaints are eligible for inclusion in the primary cohort. The rate of the 1-year outcome in the primary cohort varied significantly across hospitals with a median rate of 12.2% (95%CI: 7.9%-17.7%). With 30 hospitals, randomized at 5-month intervals in 5 steps, approximately 19,600 women are expected to be included in CODE-MI, resulting in >82% power to detect a 20% decrease in the odds of the primary outcome at a 0.05 significance level. Conclusion Routinely collected administrative health data serve as a rich and essential resource for conducting pragmatic trials assessing process change, such as CODE-MI. We demonstrated the strength of using linked administrative health data to guide the design of pragmatic clinical trials and accurately evaluate the study power.

The aim of our study was to determine a correlation between decrease of levels of atmospheric pollution (as determined by air levels of Particulate Matters with a diameter equal or less to 2.5 microns) and reduced number of hospital admissions and operations for patients with common cardiovascular diseases in Italy. We correlated number of hospital admissions and cardiovascular operations and atmospheric levels of PM.2.5 from 2015 to 2019 in Italy. This time interval was chosen because the possibility to analyze data about other established cardiovascular risk factors as reported by the European Union Eurostat. A statistically significant decrease of hospital admissions for cardiovascular and pulmonary emergencies was registered in Italy from 2015 to 2019 (p<0.01). The number also of cardiovascular operations showed a trend towards reduction with improved 30-days results, without reaching a statistically significant correlation (p =0.10). In the period 2015-2019, there was a steady decrease of atmospheric levels of pM2.5, either in urban or rural areas (p<0.01). The decrease of atmospheric levels of PMs2.5 started in 2010 and continued with a steady trend until the year 2019. In the period 2015-2019 exposure of the Italian population to established risk factors for cardiovascular diseases showed a small increase. The number of admissions and operations for non- cardiovascular and non-pulmonary diseases remained unchanged in the period 2015-2019. The findings of our study underline the possibility that decrease of atmospheric pollution may determine almost immediate decrease of cardiovascular and pulmonary diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • 12 components of Persicae semen (PS) were absorbed into plasma after administration, and PS could significantly improve the cardiac function of acute myocardial ischemia (AMI) rats. • The mechanism of PS was studied by means of systems biology (plasma component network pharmacology combined with metabolomics). • PS ameliorated AMI is associated with PI3K/Akt/NF-κB pathway and arachidonic acid metabolic. Persicae Semen is an edible Chinese herbal medicine that ameliorates myocardial ischemia. However, its pharmacodynamic properties and mechanisms of action remain unclear. This study aimed to investigate the ameliorative effect of Persicae Semen extract (PS) on acute myocardial ischemia (AMI) in rats and explore its mechanism of action. After the PS administration to rats, 12 compounds were identified in the plasma. PS can significantly improve cardiac function, regulate creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin (cTn I), α-hydroxybutyrate dehydrogenase (HBDH), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels in the serum, and ameliorate the pathological injury of AMI in rats. Metabolomics and network pharmacology of components absorbed in to plasma showed that PS may regulate the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism, then ameliorate myocardial ischemic injury. This study found that PS significantly improved cardiac function in rats with AMI, through the PI3K/Akt/NF-κB pathway and arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]

Background: Cardiac damage is common in patients with acute brain injury; however, little is known regarding cardiac-induced neurological symptoms. In the International Classification of Headache, Third Edition (ICHD-III), cardiac cephalalgia is classified as a headache caused by impaired homeostasis. Methods: This report presents four patients with acute myocardial infarction (AMI) who presented with headache that fulfilled the ICHD-III diagnostic criteria for cardiac cephalalgia. A systematic review of cardiac cephalalgia using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines is also presented. Results: Case 1: A 69-year-old man with a history of percutaneous coronary intervention (PCI) developed sudden severe occipital pain, nausea, and cold sweating. Coronary angiography (CAG) revealed occlusion of the right coronary artery (RCA). Case 2: A 66-year-old woman complained of increasing occipitalgia and chest discomfort while riding a bicycle. CAG demonstrated 99% stenosis of the left anterior descending artery. Case 3: A 54-year-old man presented with faintness, cold sweating, and occipitalgia after eating lunch. CAG detected occlusion of the RCA. Case 4: A 72-year-old man went into shock after complaining of a sudden severe headache and nausea. Vasopressors were initiated and emergency CAG was performed, which detected three-vessel disease. In all four, electrocardiography (ECG) showed ST segment elevation or depression and echocardiography revealed a left ventricular wall motion abnormality. All patients underwent PCI, which resulted in headache resolution after successful coronary reperfusion. A total of 59 cases of cardiac cephalalgia were reviewed, including the four reported here. Although the typical manifestation of cardiac cephalalgia is migraine-like pain on exertion, it may present with thunderclap headache without a trigger or chest symptoms, mimicking subarachnoid hemorrhage. ECG may not always show an abnormality. Headaches resolve after successful coronary reperfusion. Conclusions: Cardiac cephalalgia resulting from AMI can present with or without chest discomfort and even mimic the classic thunderclap headache associated with SAH. It should be recognized as a neurological emergency and treated without delay. [ABSTRACT FROM AUTHOR]

Uncoupling protein 1 (UCP1) was found exclusively in the inner membranes of the mitochondria of brown adipose tissue (BAT). We found that UCP1 was also expressed in heart tissue and significantly upregulated in isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model. The present study is to determine the underlying mechanism involved in the UCP1 upregulation in ISO-induced AMI rat model. The Ucp1−/− rats were generated by CRISPR-Cas9 system and presented decreased BAT volume. 2-months old Sprague Dawley (SD) wild-type (WT) and Ucp1−/− rats were treated with ISO intraperitoneally 30 mg/kg once a day for 3 consecutive days to establish AMI model. In saline group, the echocardiographic parameters, serum markers of myocardial injury cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), oxidant malondialdehyde (MDA), antioxidant superoxide dismutase (SOD) or fibrosis were comparable between WT and Ucp1−/− rats. ISO treatment induced worse left ventricle (LV) hypertrophy, myocardial fibrosis, increased higher cTnI, CK-MB and MDA and decreased lower SOD level in Ucp1−/− rats compared with that of WT rats. Ucp1−/− rats also presented lower myocardial phosphocreatine (PCr)/ATP-ratio, which demonstrated worse cardiac energy regulation defect. ISO treatment induced the phosphorylation of AMP-activated protein kinase (AMPK) activation, subsequently the phosphorylation of mammalian target of rapamycin (mTOR) inhibition and peroxisome proliferators-activated receptor α (PPARα) activation in WT rats, whereas activation of AMPK/mTOR/PPARα pathways significantly inhibited in Ucp1−/− rats. To sum up, UCP1 knockout aggravated ISO-induced AMI by inhibiting AMPK/mTOR/PPARα pathways in rats. Increasing UCP1 expression in heart tissue may be a cytoprotective therapeutic strategy for AMI. [ABSTRACT FROM AUTHOR]

In the recent years, a growing number of studies have shown that the occurrence of myocardial ischemia (MI) is closely related to the gut microbiota (GM). The Danshen-Honghua herb pair (DHHP), a classic combination in traditional Chinese herbal formulas, has been widely applied throughout history to cure cardiovascular disease, exhibiting remarkable clinical efficacy to treat ischemic heart disease (IHD). However, the intrinsic regulation mechanism of DHHP in treating MI remains unclear. This study aims to investigate the possible protective mechanism of DHHP in rats with acute myocardial ischemia (AMI) induced by isoproterenol (ISO) through 16S rRNA gene sequencing technique. Pharmacodynamic results showed that DHHP significantly ameliorated the pathological changes and improved the abnormal cardiac enzymes levels in the AMI rats. In addition, GM analysis demonstrated that DHHP effectively ameliorated the ISO-induced dysbiosis of the GM community, mainly by enhancing the GM diversity and increasing the relative abundance of Bacteroides, Roseburia , unclassified_f__Lachnospiraceae, and Lachnospiraceae_NK4A136_group, the abundance ratio of Bacteroidetes to Firmicutes , and decreasing the relative abundance of Escherichia-Shigella and Enterococcus. In summary, this study revealed that DHHP could improve ischemic myocardial injury in rats, and that its regulation mechanism is associated with significantly ameliorating the composition of GM, thus contributing to further our understanding of the anti-MI mechanisms of DHHP. [ABSTRACT FROM AUTHOR]

Objective: To observe the influence of acupuncture on microcirculation perfusion of the pericardium meridian and heart in acute myocardial ischemia (AMI) rats and evaluate whether acupuncture can simultaneously affect the meridians and corresponding viscera. Additionally, acupoints at different meridians were compared and whether they exert the same effects was discussed. Methods: Totally 32 Sprague-Dawley rats were subjected to left anterior descending (LAD) ligation to develop an AMI model. Rats were divided into 4 groups, including AMI, acupuncture Neiguan (PC 6), Lieque (LU 7) and Qiansanli (LI 10) groups (n=8). Eight rats received only thoracotomy (sham-operated group). The rats in the acupuncture groups received manual acupuncture at PC 6, LU 7 and LI 10 acupoints for 15 min, respectively. The microcirculation perfusion of pericardium meridian and heart was monitored by laser speckle perfusion imager (LSPI) before, during and after acupuncture manipulation for 15 min. Subsequently, the perfusion unit (PU) was calculated and analyzed by PSI System. Results: After LAD, compared to pre-acupuncture stage, the heart microcirculation perfusion (HMP) in the AMI group decreased continuously at during-acupuncture (P>0.05) and post-acupuncture stages (P<0.05), and the pericardium meridian microcirculation perfusion (PMP) showed no significant differences at 3 stages (P>0.05). Compared to pre-acupuncture stage, the PMP and HMP in PC 6 group significantly increased during acupuncture manipulation (both P<0.05), and PMP decreased obviously after acupuncture (P<0.05). The PMP in the LU 7 and LI 10 groups were slightly elevated (both P>0.05); however, they were significantly reduced after acupuncture manipulation (both P<0.05). Additionally, HMP of LI 10 group was decreased significantly during acupuncture, especially compared to pre-acupuncture stage (P<0.05). Conclusions: Acupuncture at PC 6 obviously increased the PMP and HMP in AMI rats, and the effects were superior to at LU 7 and LI 10 acupoints. It was further confirmed that acupuncture promoted qi and blood circulation, indicating that acupoint specificity exists and features a meridian-propagated effect. [ABSTRACT FROM AUTHOR]

The unexpected virulence of the COVID19 pandemic brought to significant changes of generally accepted therapeutic approaches. The consequences of these changes were difficult to define during the pandemic period. We analyzed the National Registries including 97% of hospital admissions in Italy, regarding data describing number of operations for aortic valve implantation or repair, carotid and coronary revascularization, AAA repair, and lower limb arterial reconstruction performed in the period 2015 to 2019 and in the pandemic years 2020, 2021, and 2022. Primary outcomes were number and type of surgical procedures, 30-days operative mortality. During the three years of the pandemic there was a statistically significant increase of the number of all-causes deaths in comparison with the mean of the previous five years (2015-2019). In Italy there was a total increase of all causes-deaths of 251.911 (+105900 in 2020; +66929 in 2021; and +79082 in 2022), and 73% of the excess of deaths was related with COVID19 infection and 27% occurred in COVID 19 negative patients. During the first year of the pandemic, worse clinical outcomes for hospitalized patients with CVD were registered. The medical system responded adequately and in the following two pandemic years clinical outcomes for hospitalized patients were similar with those of the pre-pandemic period. The unexpected virulence of COVID19 pandemic determined worse clinical outcomes for patients with CVD during the first year. The adopted preventive measures allowed in the following two pandemic years improved clinical outcomes, similar with those of the pre-pandemic period. [ABSTRACT FROM AUTHOR]

In traditional medicine, both Scutellaria baicalensis Georgi (SBG) and the traditional formulas composed of it have been used to treat a wide range of diseases, including cancer and cardiovascular. Wogonoside (Wog) is the biologically active flavonoid compound extracted from the root of SBG, with potential cardiovascular protective effects. However, the mechanisms underlying the protective effect of Wog on acute myocardial ischemia (AMI) have not yet been clearly elucidated. To explore the protective mechanism of Wog on AMI rats by comprehensively integrating traditional pharmacodynamics, metabolomics, and network pharmacology. The rat was pretreatment with Wog at a dose of 20 mg/kg/d and 40 mg/kg/d once daily for 10 days and then ligated the left anterior descending coronary artery of rats to establish the AMI rat model. Electrocardiogram (ECG), cardiac enzyme levels, heart weight index (HWI), Triphenyltetrazolium chloride (TTC) staining, and histopathological analyses were adopted to evaluate the protective effect of Wog on AMI rats. Moreover, a serum metabolomic-based UHPLC-Q-Orbitrap MS approach was performed to find metabolic biomarkers and metabolic pathways, and network pharmacology analysis was applied to predict targets and pathways of Wog in treating AMI. Then, the network pharmacology and metabolomic results were integrated to elucidate the mechanism of Wog in treating AMI. Finally, RT- PCR was used to detect the mRNA expression levels of PTGS1, PTGS2, ALOX5, and ALOX15 to validate the result of integrated metabolomics and network analysis. Pharmacodynamic studies suggest that Wog could effectively prevent the ST-segment of electrocardiogram elevation, reduce the myocardial infarct size, heart weight index, and cardiac enzyme levels, and alleviate cardiac histological damage in AMI rats. Metabolomics analysis showed that the disturbances of metabolic profile in AMI rats were partly corrected by Wog and the cardio-protection effects on AMI rats involved 32 differential metabolic biomarkers and 4 metabolic pathways. In addition, the integrated analysis of network pharmacology and metabolomics showed that 7 metabolic biomarkers, 6 targets, and 6 crucial pathways were the main mechanism for the therapeutic application of Wog for AMI. Moreover, the results of RT-PCR showed that PTGS1, PTGS2, ALOX5, and ALOX15 mRNA expression levels were reduced after treatment with Wog. Wog exerts cardio-protection effects on AMI rats via the regulation of multiple metabolic biomarkers, multiple targets, and multiple pathways, our current study will provide strong scientific evidence supporting the therapeutic application of Wog for AMI. [Display omitted] • An integrated strategy combining pharmacodynamics, metabolomics, and network pharmacology. • The AMI induced- metabolic disorders were partially corrected by Wog. • The cardio-protection effects of Wog on AMI involved multiple targets and multiple pathways. [ABSTRACT FROM AUTHOR]

Hypertension represents a major contributor to the development of coronary artery disease. The pathophysiological mechanisms underlying the link between hypertension and CAD are complex and include overactivation of neurohormones, accelerated development of the atherosclerotic plaque, endothelial dysfunction, altered intramyocardial coronary circulation, hypertension-mediated cardiac and vascular damage and the relationship between arterial stiffness and coronary perfusion. Blood pressure (BP) reduction is associated with a significant decrease of the risk of coronary events. Therapeutic interventions targeted to reduce BP and to improve endothelial function and coronary microvascular dysfunction, as well as to prevent left ventricular hypertrophy and dysfunction, contribute to reduce the burden of coronary disease and its acute ischemic manifestations. [Display omitted] [ABSTRACT FROM AUTHOR]

Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). In suspected ACS patients, EDICA (E arly D etection of Myocardial I schemia in Suspected Acute C oronary Syndromes by A poJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46–90] vs. 73 [56–95] μg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting. • ApoJ-Glyc detects reversible myocardial ischemia and the restoration of perfusion. • ApoJ-Glyc is a dynamic marker of transient/reversible myocardial ischemia. • ApoJ-Glyc might complement the diagnostic role of hs-Tn in the Emergency Department. [ABSTRACT FROM AUTHOR]

Objectives . Acute myocardial ischemia in the setting of acute coronary syndrome (ACS) may lead to myocardial infarction. Therefore, timely decisions, already in the pre-hospital phase, are crucial to preserving cardiac function as much as possible. Serial electrocardiography, a comparison of the acute electrocardiogram with a previously recorded (reference) ECG of the same patient, aids in identifying ischemia-induced electrocardiographic changes by correcting for interindividual ECG variability. Recently, the combination of deep learning and serial electrocardiography provided promising results in detecting emerging cardiac diseases; thus, the aim of our current study is the application of our novel Advanced Repeated Structuring and Learning Procedure (AdvRS&LP), specifically designed for acute myocardial ischemia detection in the pre-hospital phase by using serial ECG features. Approach . Data belong to the SUBTRACT study, which includes 1425 ECG pairs, 194 (14%) ACS patients, and 1035 (73%) controls. Each ECG pair was characterized by 28 serial features that, with sex and age, constituted the inputs of the AdvRS&LP, an automatic constructive procedure for creating supervised neural networks (NN). We created 100 NNs to compensate for statistical fluctuations due to random data divisions of a limited dataset. We compared the performance of the obtained NNs to a logistic regression (LR) procedure and the Glasgow program (Uni-G) in terms of area-under-the-curve (AUC) of the receiver-operating-characteristic curve, sensitivity (SE), and specificity (SP). Main Results . NNs (median AUC = 83%, median SE = 77%, and median SP = 89%) presented a statistically ( P value lower than 0.05) higher testing performance than those presented by LR (median AUC = 80%, median SE = 67%, and median SP = 81%) and by the Uni-G algorithm (median SE = 72% and median SP = 82%). Significance . In conclusion, the positive results underscore the value of serial ECG comparison in ischemia detection, and NNs created by AdvRS&LP seem to be reliable tools in terms of generalization and clinical applicability., (Creative Commons Attribution license.)

[Display omitted] • The seeds of Allium fistulosum extract (SAFE) can reduce the myocardial ischemia degree in dogs after coronary ligation. • The seeds of Allium fistulosum extract (SAFE) can decrease the infarcted area in rats and dogs after coronary ligation. • The seeds of Allium fistulosum extract (SAFE) can inhibit the elevation of serum CK and LDH in rats and dogs after coronary ligation. • The protective effect of saponins isolated from the seeds of Allium fistulosum extract on hypoxia/reoxygenation (H/R)-induced human umbilical vein endothelial cell (HUVEC) injury. Allium fistulosum (Welsh onion) is a perennial onion species that originates in eastern Asia. It is an important cooking ingredient in eastern countries, such as China, Japan, and Korea. In western countries, it is primarily used as a scallion or salad onion. According to the dictionary of Chinese drugs, the seeds of A. fistulosum , a traditional Chinese medicine, are used as tonic and aphrodisiac. The purpose of this study was to evaluate the protective effect of the seeds of A. fistulosum extract (SAFE) against acute myocardial ischemia. Rat and dog acute myocardial ischemia models were used, the model of acute myocardial ischemia in rats were divided into six groups: control group (saline, 10 mL·kg−1), model group (saline, 10 mL·kg−1), SAFE low, medium and high dose groups（50, 150, 300 mg·kg−1）and the positive control group (Xingling granule, 900 mg·kg−1), and the model of acute myocardial ischemia in dogs were also divided into the control group （saline, 2 mL·kg−1）, SAFE low, medium and high dose groups（15, 45, 90 mg·kg−1）and the positive control group (Xingling granule, 300 mg·kg−1). Myocardial ischemia degree was measured by epicardium electrocardiogram, the range of myocardial infarction was determined by quantitative histology （ N -BT staining), and serum creatine kinase (CK）and lactate dehydrogenase（LDH) content were detected by biochemical assay. Compared with the control group, the results showed that SAFE could reduce the degree of myocardial ischemia, infarcted area, and elevation of serum CK and LDH levels in rats and dogs after coronary ligation. In conclusion, SAFE can improve acute myocardial ischemia and reduce myocardial infarction in rats and dogs, and which suggests that it can achieve prevention effects of myocardial ischemia. [ABSTRACT FROM AUTHOR]

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Nociceptin/orphanin FQ (N/OFQ) and adrenergic activations play roles in promoting cardiac arrhythmia in acute myocardial ischemia but whether N/OFQ and β1-adrenergic activities interact and how they interact in the arrhythmogenesis are still unknown. We designed this study to investigate the potential interaction of N/OFQ and β1-adrenergic activities and the underlying mechanism in arrhythmogenesis in acute myocardial ischemia. Ventricular arrhythmia was evaluated in anaesthetized rats following permanent coronary artery occlusion (CAO), in presence and absence of UFP-101 (a selective antagonist of N/OFQ receptor). The changes of β1-adrenergic receptor (β1-AR) in plasma membrane of cardiomyocytes were quantitatively evaluated and the relations with the alterations of phosphorylated Raf kinase inhibitor protein (p-RKIP) and phosphorylated connexin 43 (p-Cx43) were investigated. The ventricular arrhythmia was 59% less in the animals pre-treated with UFP-101 than the placebo-treated control (difference of means = −2.41; 95% confidence interval (CI) −2.84 to −1.99; P < 0.001). Meanwhile, p-RKIP and membrane β1-AR in the myocardium were downregulated by 59% and 24%, respectively (p-RKIP: difference of means = −6.91; 95% CI -8.38 to −5.45; P < 0.001; membrane β1-AR difference of means = −27.06; 95% CI -29.89 to −24.23; P < 0.001). Artificial upregulation of RKIP by didymin significant increased β1-AR in plasma membrane of the cardiomyocytes in the animals prone to ventricular arrhythmia. The findings may suggest that activation of N/OFQ receptor in acute myocardial ischemia induces upregulation of p-RKIP, externalization of β1-adrenergic receptor and downregulation of p-Cx43 in the cardiomyocytes, which promotes ventricular arrhythmia. The mechanisms of anti-arrhythmic effect induced by antagonism of N/OFQ in acute myocardial ischemia. Acute myocardial ischemia caused significant increases of ventricular arrhythmias, p-RKIP, β1-adrenergic receptor in the plasma membrane of the cardiomyocytes but decrease of p-Cx43. Antagonism of N/OFQ receptor, by UFP-101 significantly reduces p-RKIP and β1-adrenergic receptor in the plasma membrane of the cardiomyocytes and preserve the p-Cx43, and inhibits the ventricular arrhythmias. The function of this complex is regulated in the cascade of pathway. Activation of N/OFQ receptor, in acute myocardial ischemia, induces upregulation of p-RKIP, externalization of β1-adrenergic receptor and downregulation of p-Cx43 in the cardiomyocytes, which promotes the increase of ventricular arrhythmias. Antagonism of the activation of N/OFQ, using UFP-101, extinguish the cascade of reactions and the increase of ventricular arrhythmias. "" indicating activation; "" indicating inhibition. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To explore the effects of electroacupuncture(EA) on metabolic patterns of the prefrontal cortex in rats with acute myocardial ischemia., Methods: Eighteen SD rats were randomly divided into sham group, model group and EA group, with 6 rats in each group. Rats in the model and EA groups were subject to acute myocardial ischemia by ligation of the left anterior descending coronary artery. For the EA group, EA stimulation (1 mA, 2 Hz/15 Hz, 30 min) was applied to "Shenmen"(HT7) -"Tongli"(HT5) once a day for 3 consecutive days. The histopathological changes of myocardial tissue and levels of ischemia modified albumin (IMA) in serum were determined by HE staining and ELISA, respectively. The LC-MS/MS technique was used to characterize the metabolic profiling of the prefrontal cortex. The differentially expressed metabolites were screened by principal component analysis(PCA) and partial least squares-linear discriminant analysis (PLS-LDA), and subsequently Kyoto encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis was performed., Results: Compared with the sham group, the myocardial fibers were disordered and fractured, and content of serum IMA was significantly increased in the model group ( P <0.01), which, however, were significantly decreased in the EA group ( P <0.01). With PCA and PLS-LDA, there were 18 differential metabolites between the model and sham groups. Forty-eight differential metabolites were emerged between the EA and model groups. Three metabolites associated to the sphingolipid metabolism were reversed by EA stimulation, as indicated by KEGG., Conclusion: The molecular mechanism of EA against myocardial ischemia is partially mediated by regulating sphingolipid-related metabolites in the prefrontal cortex.

Objectives: Bradyarrhythmias and Electrical conduction defects are common sequelae of acute myocardial ischemia (AMI). Many of these arrhythmias are symptomless and do not require urgent intervention while others are life threatening. Of all other potential causes myocardial ischemia is the commonest and important causative agent of acute and potentially dangerous conduction defect. This study will upgrade various aspects of patients' care with Acute MI who need TPM which will improve outcome and make the cause of death along with long term sequelae clear in such patients in our local population. To determine the in hospital outcomes of patients requiring temporary transvenous pacemaker after ST elevation MI. Methodology: This cross-sectional descriptive study was conducted at cardiology Department, MTI-KTH, Peshawar from 25 Jan, 2020 to 25 Jun, 2020. All temporary pacemakers were implanted in our Coronary Care Unit procedures and were done in an exploration room. All procedures performed by consultant cardiologists and trainee registrars. Pacemaker malfunction was described as capture failure, failure to sense, or both. Death secondary to cardiac tamponade, a systole or ventricular arrhythmias as well as improvement and need for permanent pacing was also be documented as mentioned above in operational definitions. Data was obtained after performing the procedure and during stay of patient in the coronary care unit, as determined by set protocol. The electrocatheter used was 110 cm bipolardevices of caliber 6F. Cardiac catheterization was generally via the right subclavian or internal jugular by the Seldinger's wire technique, with insertion in the apical region of the right ventricle under aseptic measures. A sensing threshold values for pacing of 0.5=2 mV were set. Pacing was initially deployed at values double the threshold voltages, using the TPM in WI mode. Results: As per in-hospital outcomes, death occurred in 14 (9.7%) died, 49 (34.0%) patients had malfunction, 10 (6.9%) patients had hematoma, 26 (18.1%) patients had fever, 27 (18.8%) patients experienced improvement while 18 (12.5%) required permanent pacing. Conclusion: In-hospital adverse outcomes were observed in a significant number of patients. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of electroacupuncture (EA) on the cardiac function, lymphatic markers, macrophage and inflammatory cytokines in acute myocardial ischemia (AMI) mice, so as to explore its mechanism in improving AMI., Methods: Male C57BL/6 mice were randomly divided into sham operation, model, EA, inhibitor and inhibitor+EA groups, with 10 mice in each group. AMI model was established by occlusion of left anterior descending coronary artery. For mice in the EA group and inhibitor+EA group, EA (1 mA, 2 Hz/15 Hz) was applied to bilateral "Shenmen"(HT7) and "Tongli"(HT5) for 30 min, once daily for consecutive 3 days. Mice in the inhibitor+EA group were given intraperitoneal injection of vascular endothelial growth factor receptor-3 (VEGFR-3) inhibitor SAR131675 30 min before the EA, while mice in the inhibitor group were given intraperitoneal injection of SAR131675 only. The electrocardiogram (ECG) of the neck-thoracic lead was recorded and analyzed by BL-420F biological function experiment system. Histopathologic changes of myocardial tissue were observed after H.E. staining. The contents of lactate dehydrogenase (LDH), cardiac troponin I (cTnI) in serum and interleukin-18 (IL-18) and interleukin-6 (IL-6) in ischemic myocardium were determined by ELISA. The expressions of hyaluronic acid receptor-1 (LYVE-1) and macrophage mar-ker CD68 (CD68) in the myocardial tissue were detected by immunofluorescence assay. The protein expression levels of vascular endothelial growth factor C (VEGF-C) and VEGFR-3 were detected by Western blot., Results: Compared with the sham operation group, the ECG-ST level, the contents of serum LDH and cTnI, and the contents of IL-18 and IL-6 in the myocardial tissue were significantly increased ( P <0.01), the expression of LYVE-1 and the protein expression levels of VEGF-C and VEGFR-3 in the myocardial tissue were significantly decreased ( P <0.01), while the number of CD68 positive cells was significantly increased ( P <0.01) in the model group. Compared with the model, inhibitor and inhibitor+EA groups, the ECG-ST level, the contents of serum LDH and cTnI, and the contents of IL-18 and IL-6 in the myocardial tissue were decreased ( P <0.01), the expression of LYVE-1 and the expression level of VEGFR-3 protein were increased ( P <0.01), while the number of CD68 positive cells was significantly decreased ( P <0.01) in the EA group. Compared with the model and inhibitor groups, the expression level of VEGF-C was increased ( P <0.01) in the EA group. Outcomes of H.E. staining showed that the myocardial fibers were disordered with a large number of inflammatory cell infiltration in the model group, which was milder in the EA group., Conclusion: Acupuncture can improve the inflammatory injury of AMI mice, which may be related to activate VEGF-C/VEGFR-3 pathway to promote lymphangiogenesis, reduce macrophage infiltration and inflammatory factors.

This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue ( P < 0.05 or P < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.

Objectives: The purpose of the study was to describe the ischemic changes occurring during percutaneous transluminal coronary angioplasty (PTCA) using a new method based on Precordial Bipolar Leads (PBL) and Precordial Unipolar Leads (PUL).Background: Ischemic ECG changes have been attributed to both systolic and diastolic injury currents. The relation between ST-segment shift and QRS changes is unclear and there is a discussion about its significance.Methods: Twelve-lead electrocardiograms (ECGs) were performed in 16 patients before PTCA balloon inflation and immediately after balloon deflation in the proximal left anterior descending coronary artery (LAD). Also, ECG data was used to generate V2-V1 PBL, average V1+V2 lead, and the correspondent loop to explore ECG and spatial vector changes.Results: (1) The V2-V1 Vs Average V1+V2 loop rotation changed from counterclockwise (CCW) to clockwise (CW) in 14 of 15 patients (93%). (2) In 12 of 16 patients (75%), there was an abrupt change of QRS vector direction, producing a "folding" of the loop. In 10 of these cases, the change occurred between 32 and 49 milliseconds after the QRS initiation. (3) In 3/16 patients the final part of the loop was "transported", without folding, to the turning point. (4) The "folding" of the loop changed the direction of the final QRS forces and the J point and ST-segment were displaced to the left and forward. (5) For this reason, repolarization began from an abnormal anterior location.Conclusions: (1) Ischemic changes in the QRS loop have a cornerstone point in which the whole loop changes. (2) Once the loop has changed its direction, there are no major modifications in the loop development, but the forces do not aim anymore to the isoelectric point. (3) Alterations of myocardial activation appear to be responsible for ST elevation in hyperacute ischemia. [ABSTRACT FROM AUTHOR]

Mitochondrial malfunction leads to the remodeling of myocardial energy metabolism during myocardial ischemia (MI). However, the alterations to the mitochondrial proteome profile during this period has not yet been clarified. An acute MI model was established by high position ligation of the left anterior descending artery in 8-week-old C57BL/6N mice. After 15 min of ligation, the animals were euthanized, and their hearts were collected. The myocardial ultrastructure was observed using transmission electron microscopy (TEM). The cardiac mitochondrial proteome profile was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses. TEM showed that the outer membrane of the mitochondria was dissolved, and the inner membrane (cristae) was corrupted and broken down extensively in the MI group. The mitochondrial membrane potential was decreased. More than 1,700 mitochondrial proteins were identified by LC-MS/MS analysis, and 119 were differentially expressed. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that endopeptidase activity regulation, the mitochondrial inner membrane, oxidative phosphorylation, the hypoxia-inducible factor-1 signaling pathway, the pentose phosphate pathway and the peroxisome proliferator-activated receptor signaling pathway were involved in the pathophysiological process in the early stage of acute MI. Extensive and substantial changes in the mitochondrial proteins as well as mitochondrial microstructural damage occur in the early stages of acute MI. In the present study, the series of proteins crucially involved in the pathways of mitochondrial dysfunction and metabolism were identified. Further studies are needed to clarify the roles of these proteins in myocardial metabolism remodeling during acute MI injury. [ABSTRACT FROM AUTHOR]

Cardiac remodeling is the primary pathological feature of chronic heart failure. Prompt inhibition of remodeling in acute coronary syndrome has been a standard procedure, but the morbidity and mortality are still high. Exploring the characteristics of ischemia in much earlier stages and identifying its biomarkers are essential for introducing novel mechanisms and therapeutic strategies. Metabolic and structural remodeling of mitochondrion is identified to play key roles in ischemic heart disease. The mitochondrial metabolic features in early ischemia have not previously been described. In the present study, we established a mouse heart in early ischemia and explored the mitochondrial metabolic profile using metabolomics analysis. We also discussed the role of mitochondrion in the global cardiac metabolism. Transmission electron microscopy revealed that mitochondrial structural injury was invoked at 8 minutes post-coronary occlusion. In total, 75 metabolites in myocardium and 26 in mitochondria were screened out. About 23% of the differentiated metabolites in mitochondria overlapped with the differentiated metabolites in myocardium; Total 81% of the perturbed metabolic pathway in mitochondria overlapped with the perturbed pathway in myocardium, and these pathways accounted for 50% of the perturbed pathway in myocardium. Purine metabolism was striking and mechanically important. In conclusion, in the early ischemia, myocardium exacerbated metabolic remodeling. Mitochondrion was a contributor to the myocardial metabolic disorder. Purine metabolism may be a potential biomarker for early ischemia diagnosis. Our study introduced a perspective for prompt identification of ischemia.

Objective: To observe the effect of electroacupuncture (EA) on the expression of myocardial protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in acute myocardial ischemia (AMI) rats., Methods: Thirty male SD rats were randomly divided into control, model and EA groups ( n =10 in each group). The AMI model was established by occlusion of the descending anterior branch (DAB) of the left coronary artery. EA (2 Hz, 1-2 mA) was applied to bilateral "Shenmen" (HT7) and "Tongli" (HT5) for 20 min, once daily for consecutive 7 days. The electrocardiogram (ECG) of nape-xiphoid lead was recorded for assessing changes of myocardial ischemia. Histopathologic changes of the ischemic myocardial tissue were observed after H.E. staining and ultra-microstructural changes of cardiomyocytes observed by transmission electron microscopy (TEM). The expression levels of Akt, phosphorylated-Akt (p-Akt), mTOR and phosphorylated-mTOR (p-mTOR) in the myocardium were detected by Western blot, followed by calculating the ratios of p-Akt/Akt and p-mTOR/mTOR., Results: Following ligature of DAB, the ECG-ST level was significantly increased in the model group in comparison with the control group ( P <0.01). At 30 min after treatment, the ECG-ST level decreased significantly compared with the model group ( P <0.01). At the end of the 7-day treatment period, the ECG-ST level increased compared with the model group ( P <0.05). The levels of myocardial p-Akt and p-mTOR protein expression, and the ratios of p-Akt/Akt and p-mTOR/mTOR were significantly lower in the model group than those in the control group ( P <0.01), and considerably increased in the EA group than in the model group ( P <0.01). No significant differences were found among the three groups in the expression levels of Akt and mTOR proteins ( P >0.05). Outcomes of H.E. staining and TEM showed damage of mitochondria and occurrence of a large number of autophagosomes in myocardiocytes in the model group, which was milder in the EA group., Conclusion: EA at HT5 and HT7 can improve AMI in AMI rats, which may be related to its effect in facilitating Akt/mTOR signaling.