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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.

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the “sweating” primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Salvia miltiorrhiza Bunge (SM) is a widespread herbal therapy for myocardial ischemia (MI). Nevertheless, the therapeutic signaling networks of SM extract on MI is yet unknown. Emerging evidences suggested that alterations in cardiac metabolite influences host metabolism and accelerates MI progression. Herein, we employed an isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model to confirm the pharmacological effects of SM extract (0.8, 0.9, 1.8 g/kg/day) via assessment of the histopathological alterations that occur within the heart tissue and associated cytokines; we also examined the underlying SM extract-mediated signaling networks using untargeted metabolomics. The results indicated that 25 compounds with a relative content higher than 1 % in SM aqueous extract were identified using LC-MS/MS analysis, which included salvianolic acid B, lithospermic acid, salvianolic acid A, and caffeic acid as main components. An in vivo experiment showed that pretreatment with SM extract attenuated ISO-induced myocardial injury, shown as decreased myocardial ischemic size, transformed electrocardiographic, histopathological, and serum biochemical aberrations, reduced levels of proinflammatory cytokines, inhibited oxidative stress (OS), and reversed the trepidations of the cardiac tissue metabolic profiles. Metabolomics analysis shows that the levels of 24 differential metabolites (DMs) approached the same value as controls after SM extract therapy, which were primarily involved in histidine; alanine, aspartate, and glutamate; glycerophospholipid; and glycine, serine, and threonine metabolisms through metabolic pathway analysis. Correlation analysis demonstrated that the levels of modulatory effects of SM extract on the inflammation and OS were related to alterations in endogenous metabolites. Overall, SM extract demonstrated significant cardioprotective effects in an ISO-induced AMI rat model, alleviating myocardial injury, inflammation and oxidative stress, with metabolomics analysis indicating potential therapeutic pathways for myocardial ischemia.

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]

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.

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.

Abstract 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.

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 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]

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]

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.

[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]

Background: In the prehospital triage of patients presenting with symptoms suggestive of acute myocardial ischemia, reliable myocardial ischemia detection in the electrocardiogram (ECG) is pivotal. Due to large interindividual variability and overlap between ischemic and nonischemic ECG-patterns, incorporation of a previous elective (reference) ECG may improve accuracy. The aim of the current study was to explore the potential value of serial ECG analysis using subtraction electrocardiography.Methods: SUBTRACT is a multicenter retrospective observational study, including patients who were prehospitally evaluated for acute myocardial ischemia. For each patient, an elective previously recorded reference ECG was subtracted from the ambulance ECG. Patients were classified as myocardial ischemia cases or controls, based on the in-hospital diagnosis. The diagnostic performance of subtraction electrocardiography was tested using logistic regression of 28 variables describing the differences between the reference and ambulance ECGs. The Uni-G ECG Analysis Program was used for state-of-the-art single-ECG interpretation of the ambulance ECG.Results: In 1,229 patients, the mean area-under-the-curve of subtraction electrocardiography was 0.80 (95%CI: 0.77-0.82). The performance of our new method was comparable to single-ECG analysis using the Uni-G algorithm: sensitivities were 66% versus 67% (p-value > .05), respectively; specificities were 80% versus 81% (p-value > .05), respectively.Conclusions: In our initial exploration, the diagnostic performance of subtraction electrocardiography for the detection of acute myocardial ischemia proved equal to that of state-of-the-art automated single-ECG analysis by the Uni-G algorithm. Possibly, refinement of both algorithms, or even integration of the two, could surpass current electrocardiographic myocardial ischemia detection. [ABSTRACT FROM AUTHOR]

The hippocampus is involved in the regulation of the autonomic nervous system, together with the hypothalamus and brainstem nuclei, such as the paraventricular nucleus and nucleus tractus solitarius. The vagus nerve-nucleus tractus solitarius pathway has an important role in cardiovascular reflex regulation. Myocardial ischemia has been shown to cause changes in the autonomic nervous system, affecting the dynamic equilibrium of the sympathetic and vagal nerves. However, it remains poorly understood how the hippocampus communicates with brainstem nuclei to regulate the autonomic nervous system and alleviate myocardial ischemic tissue damage. A rat model of acute myocardial ischemia (AMI) was made by ligating the left anterior descending branch of the coronary artery. Three days before ischemia, the hippocampal CA1 region was damaged. Then, 3 days after ischemia, electroacupuncture (EA) at Shenmen (HT7)-Tongli (HT5) was performed (continuous wave, 1 mA, 2 Hz, duration of 30 minutes). Cluster analysis of firing patterns showed that one type of neuron was found in rats in the sham and AMI groups. Three types of neurons were observed in the AMI + EA group. Six types of neurons were found in the AMI + EA + Lesion group. Correlation analysis showed that the frequency of vagus nerve discharge in each group was negatively correlated with heart rate (HR) (P < 0.05, r = −0.424), and positively correlated with mean arterial pressure (MAP) (P < 0.05, r = 0.40987) and the rate-pressure product (RPP) (P < 0.05, r = 0.4252). The total frequency of the nucleus tractus solitarius discharge in each group was positively correlated with vagus nerve discharge (P < 0.01, r = 0.7021), but not with hemodynamic index (HR: P > 0.05, r = −0.03263; MAP: P > 0.05, r = −0.08993; RPP: P > 0.05, r = −0.03263). Some neurons (Neuron C) were negatively correlated with vagus nerve discharge, HR, MAP and RPP in the AMI + EA group (vagus nerve discharge: P < 0.05, r = −0.87749; HR: P < 0.01, r = −0.91902; MAP: P < 0.05, r = −0.85691; RPP: P < 0.01, r = −0.91902). Some neurons (Neurons C, D and E) were positively correlated with vagus nerve discharge, HR, MAP and RPP in the AMI + EA + Lesion group (vagus nerve discharge: P < 0.01, r = 0.8905, P < 0.01, r = 0.9725, P < 0.01, r = 0.9054; HR: P < 0.01, r = 0.9347, P < 0.01, r = 0.9089, P < 0.05, r = 0.8247; MAP: P < 0.05, r = 0.8474, P < 0.01, r = 0.9691, P < 0.01, r = 0.9027; RPP: P < 0.05, r = 0.8637, P < 0.01, r = 0.9407, P < 0.01, r = 0.9027). These findings show that the hippocampus-nucleus tractus solitarius-vagus nerve pathway is involved in the cardioprotective effect of EA at the heart meridian. Some interneurons in the nucleus tractus solitarius may play a particularly important role in the cardiomodulatory process.

Abstact Background To evaluate the left ventricular (LV) longitudinal function changes in rabbits after acute occlusion of the left anterior descending artery (LAD) by two-dimensional speckle tracking imaging (2D–STI). Methods Forty-eight New Zealand white rabbits underwent echocardiography examination. EchoPAC was used to measure LV peak systolic longitudinal strain (LS) of the endocardium, middle myocardium, and epicardium, peak longitudinal strain rate (LSr), segmental and global longitudinal rotation (LR) degrees. Ligated the LAD and repeated all measurements after 10 min. Results Peak LS and LSr were significantly different between the preoperative and postoperative rabbits among most LV walls (P

Emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease. Here, we performed 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabolomics to investigate the gut microbiome and metabolomes of cecal contents in the isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rats. As expected, considerable gut microbiota alterations were observed in the AMI rats compared with the control rats, paralleling with intestinal inflammation and apoptosis. At phylum level, the abundance of Firmicutes was significantly decreased, whereas the abundance of Bacteroidetes and Spirochaetae was strikingly enriched in the AMI group. At genus level, the significant alteration of genera Treponema 2, Rikenellaceae RC9 gut group, Prevotellaceae UCG-003, and Bacteroides may contribute to the pathogenesis of AMI. These altered microbiota might influence the intestinal permeability and subsequently impair intestinal barrier and stimulate gut inflammation. Consistently, significantly metabolic differences of cecal contents between the AMI and control groups were revealed, and threonic acid, L-urobilin and L-urobilinogen were considered the most associated cecal metabolites with AMI. These strikingly altered metabolites were mainly related to energy metabolism and oxidative stress which could lead to apoptosis and further affect gut barrier. Ultimately, we revealed the potential link of these altered gut microbiota/metabolomes and intestinal inflammatory factors and apoptotic proteins and further confirmed their intimate connections with intestinal inflammation and gut barrier. Our findings depict uncovered potential relationship among the gut microbiome, cecal metabolomes and AMI.

BackgroundAcoustic cardiography is a hybrid technique that couples heart sounds recording with ECG providing insights into electrical-mechanical activity of the heart in an unsupervised, non-invasive and inexpensive manner. During myocardial ischemia hemodynamic abnormalities appear in the first minutes and we hypothesize a putative diagnostic role of acoustic cardiography for prompt detection of cardiac dysfunction for future patient management improvement.Methods and ResultsTen female Swiss large white pigs underwent permanent distal coronary occlusion as a model of acute myocardial ischemia. Acoustic cardiography analyses were performed prior, during and after coronary occlusion. Pressure-volume analysis was conducted in parallel as an invasive method of hemodynamic assessment for comparison. Similar systolic and diastolic intervals obtained with the two techniques were significantly correlated [Q to min dP/dt vs. Q to second heart sound (r2 = 0.9583, p < 0.0001), PV diastolic filling time vs. AC perfusion time (r2 = 0.9686, p < 0.0001)]. Indexes of systolic and diastolic impairment correlated with quantifiable features of heart sounds [Tau vs. fourth heart sound Display Value (r2 = 0.2721, p < 0.0001) cardiac output vs. third heart sound Display Value (r2 = 0.0791 p = 0.0023)]. Additionally, acoustic cardiography diastolic time (AUC 0.675, p = 0.008), perfusion time (AUC 0.649, p = 0.024) and third heart sound Display Value (AUC 0.654, p = 0.019) emerged as possible indicators of coronary occlusion. Finally, these three parameters, when joined with heart rate into a composite joint-index, represent the best model in our experience for ischemia detection (AUC 0.770, p < 0.001).ConclusionIn the rapidly evolving setting of acute myocardial ischemia, acoustic cardiography provided meaningful insights of mechanical dysfunction in a prompt and non-invasive manner. These findings should propel interest in resurrecting this technique for future translational studies as well as reconsidering its reintroduction in the clinical setting.

Background: Acoustic cardiography is a hybrid technique that couples heart sounds recording with ECG providing insights into electrical-mechanical activity of the heart in an unsupervised, non-invasive and inexpensive manner. During myocardial ischemia hemodynamic abnormalities appear in the first minutes and we hypothesize a putative diagnostic role of acoustic cardiography for prompt detection of cardiac dysfunction for future patient management improvement. Methods and Results: Ten female Swiss large white pigs underwent permanent distal coronary occlusion as a model of acute myocardial ischemia. Acoustic cardiography analyses were performed prior, during and after coronary occlusion. Pressure-volume analysis was conducted in parallel as an invasive method of hemodynamic assessment for comparison. Similar systolic and diastolic intervals obtained with the two techniques were significantly correlated [Q to min dP/dt vs. Q to second heart sound (r 2 = 0.9583, p < 0.0001), PV diastolic filling time vs. AC perfusion time (r 2 = 0.9686, p < 0.0001)]. Indexes of systolic and diastolic impairment correlated with quantifiable features of heart sounds [Tau vs. fourth heart sound Display Value (r 2 = 0.2721, p < 0.0001) cardiac output vs. third heart sound Display Value (r 2 = 0.0791 p = 0.0023)]. Additionally, acoustic cardiography diastolic time (AUC 0.675, p = 0.008), perfusion time (AUC 0.649, p = 0.024) and third heart sound Display Value (AUC 0.654, p = 0.019) emerged as possible indicators of coronary occlusion. Finally, these three parameters, when joined with heart rate into a composite joint-index, represent the best model in our experience for ischemia detection (AUC 0.770, p < 0.001). Conclusion: In the rapidly evolving setting of acute myocardial ischemia, acoustic cardiography provided meaningful insights of mechanical dysfunction in a prompt and non-invasive manner. These findings should propel interest in resurrecting this technique for future translational studies as well as reconsidering its reintroduction in the clinical setting. [ABSTRACT FROM AUTHOR]

Emerging evidence highlights the role of gut microbiota in regulating the pathogenesis of coronary heart disease. Here, we performed 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabolomics to investigate the gut microbiome and metabolomes of cecal contents in the isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rats. As expected, considerable gut microbiota alterations were observed in the AMI rats compared with the control rats, paralleling with intestinal inflammation and apoptosis. At phylum level, the abundance of Firmicutes was significantly decreased, whereas the abundance of Bacteroidetes and Spirochaetae was strikingly enriched in the AMI group. At genus level, the significant alteration of genera Treponema 2 , Rikenellaceae RC9 gut group , Prevotellaceae UCG-003 , and Bacteroides may contribute to the pathogenesis of AMI. These altered microbiota might influence the intestinal permeability and subsequently impair intestinal barrier and stimulate gut inflammation. Consistently, significantly metabolic differences of cecal contents between the AMI and control groups were revealed, and threonic acid, L-urobilin and L-urobilinogen were considered the most associated cecal metabolites with AMI. These strikingly altered metabolites were mainly related to energy metabolism and oxidative stress which could lead to apoptosis and further affect gut barrier. Ultimately, we revealed the potential link of these altered gut microbiota/metabolomes and intestinal inflammatory factors and apoptotic proteins and further confirmed their intimate connections with intestinal inflammation and gut barrier. Our findings depict uncovered potential relationship among the gut microbiome, cecal metabolomes and AMI. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the expression of plasminogen activator inhibitor-1 (PAI-1) and microRNA (miR)-30b in the blood of patients with acute myocardial ischemia (AMI) and in the blood and myocardial tissue of mice with AMI. In addition, the present study aimed to identify the mechanism of action of miR-30b in AMI. A total of 36 patients with AMI were included in the present study and 28 healthy subjects were included as a control. Peripheral blood was collected from all subjects. For animal experiments, mice in the AMI group received an intraperitoneal injection of pituitrin (20 U/kg), whereas mice in the negative control group received an intraperitoneal injection of the same volume of saline. Blood and myocardial tissue was collected from all mice for analysis. Reverse transcription-quantitative polymerase chain reaction was performed to determine the expression of PAI-1 mRNA and miR-30b in the serum and myocardial tissue. An enzyme-linked immunosorbent assay was performed to measure the expression of PAI-1 protein in the serum of humans and mice, whereas western blotting was performed to determine the expression of PAI-1 protein in mouse myocardial tissue. Catalase, glutathione peroxidase and superoxide dismutase activity was measured using an automatic biochemical analyzer. A dual luciferase assay was performed to identify the interactions between PAI-1 mRNA and miR-30b. The results indicated that patients with AMI have higher PAI-1 levels and lower miR-30b expression in the peripheral blood compared with healthy subjects. AMI damaged the myocardium tissue of mice and reduced catalase, glutathione peroxidase and superoxide dismutase activity. Mice that have undergone AMI exhibit increased PAI-1 levels but decreased miR-30b expression in the peripheral blood and myocardial tissues. It was also demonstrated that miR-30b is able to bind to the 3'-untranslated region of PAI-1 mRNA to regulate its expression. The present study demonstrates that patients with AMI exhibit decreased miR-30b expression and elevated PAI-1 expression in the peripheral blood. miR-30b may therefore inhibit the damage to myocardial cells that occurs following AMI and protect myocardial cell function by targeting PAI-1 expression. [ABSTRACT FROM AUTHOR]

Trichosanthes pericarpium (TP) had been widely used to cure patients of cardiovascular disease for 2,000 years in China. This study aims to extend our previous work to explore the mechanism underlying the protective effect of TP on acute myocardial ischemia (AMI). We hypothesized that TP may display its protective effect on AMI by promoting the mobilization of endothelial progenitor cells (EPC) via up-regulating the expression level of vascular endothelial growth factor (VEGF), endothelial nitric oxide syntheses (eNOS), nitric oxide (NO), and matrix metalloproteinase 9 (MMP-9) in AMI rats. To confirm this hypothesis, we treated AMI model rats with intragastrical administration of TP aqueous extract (TPAE), and examined both changes in the number of CEPC, and the expression levels of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content in these rats. Rats in each group were randomly divided into seven subgroups. From day 1 to 7 following AMI modeling, rats in these subgroups was sequentially phlebotomized from their celiac artery after being anesthetized by chloral hydrate. We found that, compared with the AMI model rats, in rats treated by TPAE, the CEPC counts, the expression of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content all increased more rapidly 7 days after AMI and remained at higher level (P < 0.05 or P < 0.01). Our results showed that, in AMI rats, the TPAE could significantly promote the mobilization of EPC and up-regulate the expression level of VEGF, eNOS, NO, and MMP-9 in myocardium and their plasma content. Therefore, our results suggest that TAPE may regulate EPC mobilization through up-regulating the expression level of VEGF, eNOS, NO and MMP-9 in the myocardium of AMI rats.

Trichosanthes pericarpium (TP) had been widely used to cure patients of cardiovascular disease for 2,000 years in China. This study aims to extend our previous work to explore themechanismunderlying the protective effect of TP on acutemyocardial ischemia (AMI). We hypothesized that TP may display its protective effect on AMI by promoting the mobilization of endothelial progenitor cells (EPC) via up-regulating the expression level of vascular endothelial growth factor (VEGF), endothelial nitric oxide syntheses (eNOS), nitric oxide (NO), and matrix metalloproteinase 9 (MMP-9) in AMI rats. To confirm this hypothesis, we treated AMI model rats with intragastrical administration of TP aqueous extract (TPAE), and examined both changes in the number of CEPC, and the expression levels of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content in these rats. Rats in each group were randomly divided into seven subgroups. From day 1 to 7 following AMI modeling, rats in these subgroups was sequentially phlebotomized from their celiac artery after being anesthetized by chloral hydrate. We found that, compared with the AMI model rats, in rats treated by TPAE, the CEPC counts, the expression of VEGF, eNOS, NO, and MMP-9 in myocardial tissue and their plasma content all increased more rapidly 7 days after AMI and remained at higher level (P < 0.05 or P < 0.01). Our results showed that, in AMI rats, the TPAE could significantly promote the mobilization of EPC and up-regulate the expression level of VEGF, eNOS, NO, and MMP-9 in myocardium and their plasma content. Therefore, our results suggest that TAPE may regulate EPC mobilization through up-regulating the expression level of VEGF, eNOS, NO and MMP-9 in the myocardium of AMI rats. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is the leading cause of death worldwide. Myocardial ischemia (MI) is the most common underlying causal disorder for SCD. Metabolic risks leading to SCD during acute MI are still not fully understood. Here, using tissue metabolomics, we aimed to investigate myocardial metabolic alterations relevant to SCD events in an acute MI rat model induced by coronary artery ligation (CAL). Thirty-four rats were successfully performed CAL, of which 13 developed lethal ventricular tachyarrhythmia (LVTA)-SCD and 7 developed severe atrioventricular block (AB)-SCD. Fourteen rats that survived within 70 min after the ligation were served as peer controls. The partial least squares-discriminant analysis plots demonstrated clear separations between the SCD rats and controls, indicating obvious differences in myocardial metabolome between these rats. The levels of isoleucine, lactate, glutamate choline, phosphorylcholine, taurine and asparagine in ischemic myocardia were positively associated with LVTA-SCD events; in contrast, the levels of alanine, urea, phenylalanine, linoleic acid, elaidic acid and stearic acid were inversely correlated with LVTA-SCD events. The levels of glutamate and urea were positively and negatively relevant to AB-SCD events, respectively. The dangerous metabolites indicated that lower levels of energy substrates, severe hypoxia, the inhibition of transamination and hyper sympathetic excitement and reactive oxygen species in myocardia were vulnerable to SCD during acute MI. The results suggest fatal metabolic alterations correlated with SCD events during acute MI, which could offer novel clues for the prevention or treatment of acute MI-related SCD. [ABSTRACT FROM PUBLISHER]

The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-a levels were subsequently measured. Myocardial levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were also determined. Myocardial infarction size (IS) was determined by 2,3,5-triphenyltetrazolium chloride staining. Myocardial expression of hypoxia inducible factor (HIF)-1a and phosphorylated p38 mitogen-activated protein kinase (P-p38 MAPK) protein was measured using western blotting. The results demonstrated that HMGB1 significantly decreased serum levels of cTnI, IL-6 and TNF-a and myocardial IS in I/R rats compared with the sham group (all P<0.05). HMGB1 also significantly decreased and increased myocardial levels of MDA and SOD, respectively (both P<0.05). HMGB1 significantly increased myocardial expression of HIF-1α and decreased expression of P-p38 MAPK following I/R (both P<0.05). These effects of HMGB1 occurred in a dosedependent manner. The results of the current study indicate that the cardioprotective effects of intravenous HMGB1 are associated with increased myocardial expression of HIF-1a via inhibition of P-p38 MAPK expression, leading to inhibition of the P-p38 MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

[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]

Background: The prevalence of ischemic heart disease is high. Few recent studies have investigated the periods of sick leave of these patients. Our aim is to determine the length of sick leave after an acute coronary syndrome, its costs, associated factors and to assess the use of antidepressants and/or anxiolytics.Methods: An observational study of a retrospective cohort of patients on sick leave due to ischemic heart disease in a health region between 2008-2011, with follow-up until the first return to work, death, or end of the study (31/12/2012).Measurements: length of sick leave, sociodemographic variables and medical prescriptions.Results: Four hundred and ninety-seven patients (mean age 53 years, 90.7% male), diagnosed with acute myocardial infarction (60%), angina pectoris (20.7%) or chronic form of ischemic heart disease (19.1%). Thirty-seven per cent of patients took anxiolytics the year after diagnosis and 15% took antidepressants. The average duration of sick leave was 177 days (95% CI: 163-191 days). Patients diagnosed with acute myocardial infarction returned to work after a mean of 192 days, compared to 128 days in cases with angina pectoris. Patients who took antidepressants during the year after diagnosis returned to work after a mean of 240 days. The mean work productivity loss was estimated to be 9,673 euros/person.Conclusions: The mean duration of sick leave due to ischemic heart disease was almost six months. Consumption of psychotropic medication doubled after the event. Older age, suffering an acute myocardial infarction and taking antidepressants were associated with a longer sick leave period. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is believed to be involved in numerous physiological and pathophysiological processes, and now it is recognized as the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide; however, the effects of H2S on inflammatory factors in acute myocardial ischemia injury in rats have not been clarified. In the present study, sodium hydrosulfide (NaHS) was used as the H2S donor. Thirty-six male Sprague Dawley rats were randomly divided into five groups: Sham, ischemia, ischemia + low-dose (0.78 mg/kg) NaHS, ischemia + medium-dose (1.56 mg/kg) NaHS, ischemia + high-dose (3.12 mg/kg) NaHS and ischemia + propargylglycine (PPG) (30 mg/kg). The rats in each group were sacrificed 6 h after the surgery for sample collection. Compared with the ischemia group, the cardiac damage in the rats in the ischemia + NaHS groups was significantly reduced, particularly in the high-dose group; in the ischemia + PPG group, the myocardial injury was aggravated compared with that in the ischemia group. Compared with the ischemia group, the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the serum of rats in the ischemia + medium- and high-dose NaHS groups were significantly reduced, and the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) protein in the myocardial tissues of rats was significantly reduced. In the ischemia + PPG group, the TNF-α, IL-1β and IL-6 levels in the serum were significantly increased, the expression of ICAM-1 mRNA was increased, although without a significant difference, and the expression of NF-κB was increased. The findings of the present study provide novel evidence for the dual effects of H2S on acute myocardial ischemia injury via the modulation of inflammatory factors. [ABSTRACT FROM AUTHOR]

Objective To observe the effects antiarrhythmic peptide 10 (AAP10) aon acute ventricular arrhythmia and the phosphorylation state of ischemic myocardium connexin. Methods Acute total ischemia and partial ischemia models were established by ceasing perfusion and ligating the left anterior descending coronary artery in SD rats. The effects of AAP10 (1 mg/L) on the incidence rate of ischemia–induced ventricular arrhythmia were observed. The ischemic myocardium was sampled to detect total–Cx43 and NP–Cx43 by immunofluorescent staining and western blotting. the total–Cx43 expression was detected through image analysis system by semi–quantitative analysis. Results AAP10 could significantly decrease the incidence of ischemia–induced ventricular tachycardia and ventricular fibrillation. During ischemic stage, total ischemia (TI) and AAP10 total ischemia (ATI) groups were compared with partial ischemia (PI) and AAP10 partial ischemia (API) groups. The rates of incidence for arrhythmia in the ATI and API groups (10% and 0%) were lower than those in the TI and PI groups (60% and 45%). The difference between the two groups was statistically significant ( P =0.019, P =0.020). The semi–quantitative analysis results of the ischemic myocardium showed that the total–Cx43 protein expression distribution areas for TI, ATI, PI and API groups were significantly decreased compared with the control group. On the other hand, the NP–Cx43 distribution areas of TI, ATI, PI and API groups were significantly increased compared with the control group ( P >0.05). AAP10 could increase the total–Cx43 expression in the ischemic area and decrease the NP–Cx43 expression. Western blot results were consistent with the results of immunofluorescence staining. Conclusions AAP10 can significantly decrease the rate of incidence of acute ischemia–induced ventricular tachycardia and ventricular fibrillation. Acute ischemic ventricular arrhythmias may have a relationship with the decreased phosphorylation of Cx43 induced by ischemia. AAP10 may stimulate the phosphorylation of Cx43 by increasing the total–Cx43 expression and decreasing the NP–Cx43 expression in the ischemic area, so as to decrease ventricular arrhythmia. [ABSTRACT FROM AUTHOR]

Objective A new cardiac 'electrical' biomarker (CEB) for detection of 12-lead electrocardiogram (ECG) changes indicative of acute myocardial ischemic injury has been identified. Objective was to test CEB diagnostic accuracy. Methods This is a blinded, observational retrospective case-control, noninferiority study. A total of 508 ECGs obtained from archived digital databases were interpreted by cardiologist and emergency physician (EP) blinded reference standards for presence of acute myocardial ischemic injury. CEB was constructed from three ECG cardiac monitoring leads using nonlinear modeling. Comparative active controls included ST voltage changes (J-point, ST area under curve) and a computerized ECG interpretive algorithm (ECGI). Training set of 141 ECGs identified CEB cutoffs by receiver-operating-characteristic (ROC) analysis. Test set of 367 ECGs was analyzed for validation. Poor-quality ECGs were excluded. Sensitivity, specificity, and negative and positive predictive values were calculated with 95% confidence intervals. Adjudication was performed by consensus. Results CEB demonstrated noninferiority to all active controls by hypothesis testing. CEB adjudication demonstrated 85.3-94.4% sensitivity, 92.5-93.0% specificity, 93.8-98.6% negative predictive value, and 74.6-83.5% positive predictive value. CEB was superior against all active controls in EP analysis, and against ST area under curve and ECGI by cardiologist. Conclusion CEB detects acute myocardial ischemic injury with high diagnostic accuracy. CEB is instantly constructed from three ECG leads on the cardiac monitor and displayed instantly allowing immediate cost-effective identification of patients with acute ischemic injury during cardiac rhythm monitoring. [ABSTRACT FROM AUTHOR]