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ulmonary embolism (PE) can be difficult to diagnose on clinical grounds as it often presents with nonspecific symptoms. 1 Clinical instability can delay or prevent the execution of an effective diagnostic strategy, with resulting delay in providing appropriate therapy. Prompt diagnosis of PE heavily relies on clinical suspicion. The electrocardiogram (ECG), one of the first examinations to be performed in cases of suspected PE, has been widely studied. 2-7 ECG abnormalities can be seen in 70-80% of patients, varying from the typical S1Q3T3 pattern to no specific changes. However, only very rarely does a PE produce an ECG pattern mimicking acute myocardial infarction (AMI). We describe such a case in the following report. Furthermore, the angiography showed the coronary arteries were normal and the right main pulmonary artery was partially occluded by large pulmonary emboli, despite the acute phase ECG pattern suggestive of AMI, and we recorded in detail the ECG changes which also pointed to the diagnosis of PE. It shows the importance of recognition of various ECG changes in patients with PE. Case ReportA 35-year-old Chinese man was admitted to the hospital because of a 4-week history of a painful right leg. The patient had no significant past medical history and took no medications. The family history was unremarkable for any acute or chronic medical problems. He had no drug allergies and no history of past surgeries, smoking and drinking.He was referred to the radiology department for a Doppler scan of lower extremities. While waiting for the examination, he suddenly collapsed while standing and lost consciousness for approximately 3 min. He recovered spontaneously and had severe chest pain and dyspnea associated with diaphoresis. The patient was then transferred to the cardiology emergency department. In the emergency department, his blood pressure was 72/43 mmHg, his heart rate was regular at 80 beats/min and his respiratory rate was 23 breaths/min. An arterial blood gas test showed an arterial oxygen pressure of 71 mmHg (oxygen saturation was 90%) and a carbon dioxide pressure of 36 mmHg while the patient was breathing 6L of oxygen by face mask.Physical examination revealed a well developed, well nourished man, who knew his identity, whereabouts and the date, and focal neurologic findings were not present when examined. The chest was clear to auscultation and percussion bilaterally. Findings of heart and abdominal examinations were unremarkable, and lower extremities were without edema.Initial investigations revealed that concentrations of complete blood cell count, serum electrolytes, glucose, blood urea and creatinine were normal. The initial ECG ( Figure 1A) showed a normal sinus rate of 80 beats/min with incomplete right bundle branch block (RBBB), ST elevations in leads V1-4, s waves in leads I and V5,6, q wave in lead III. An initial diagnosis of acute anterior myocardial infarction was made. The inotropic agent dopamine was initiated to maintain adequate tissue perfusion, and the patient was administ...

Human umbilical cord mesenchymal stem cell‐derived exosomes (hucMSC‐exosomes) have been implicated as a novel therapeutic approach for tissue injury repair and regeneration, but the effects of hucMSC‐exosomes on coxsackievirus B3 (CVB3)‐induced myocarditis remain unknown. The object of the present study is to investigate whether hucMSC‐exosomes have therapeutic effects on CVB3‐induced myocarditis (VMC). HucMSC‐exosomes were identified using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot. The purified hucMSC‐exosomes tagged with PKH26 were tail intravenously injected into VMC model mice in vivo and used to administrate CVB3‐infected human cardiomyocytes (HCMs) in vitro, respectively. The effects of hucMSC‐exosomes on myocardial pathology injury, proinflammatory cytokines and cardiac function were evaluated through haematoxylin and eosin (H&E) staining, quantitative polymerase chain reaction (qPCR) and Doppler echocardiography. The anti‐apoptosis role and potential mechanism of hucMSC‐exosomes were explored using TUNEL staining, flow cytometry, immunohistochemistry, Ad‐mRFP‐GFP‐LC3 transduction and Western blot. In vivo results showed that hucMSC‐exosomes (50 μg iv) significantly alleviated myocardium injury, shrank the production of proinflammatory cytokines and improved cardiac function. Moreover, in vitro data showed that hucMSC‐exosomes (50 μg/mL) inhibited the apoptosis of CVB3‐infected HCM through increasing pAMPK/AMPK ratio and up‐regulating autophagy proteins LC3II/I, BECLIN‐1 and anti‐apoptosis protein BCL‐2 as well as decreasing pmTOR/mTOR ratio, promoting the degradation of autophagy flux protein P62 and down‐regulating apoptosis protein BAX. In conclusion, hucMSC‐exosomes could alleviate CVB3‐induced myocarditis via activating AMPK/mTOR‐mediated autophagy flux pathway to attenuate cardiomyocyte apoptosis, which will be benefit for MSC‐exosome therapy of myocarditis in the future.

BackgroundIn recent years, catheter ablation has increasingly been used for ablation of idiopathic premature ventricular complexes (PVCs) or ventricular tachycardias (IVTs). However, the mapping and catheter ablation of the arrhythmias originating from the vicinity of tricuspid annulus (TA) may not be fully understood. This study aimed to investigate electrophysiologic characteristics and effects of radiofrequency catheter ablation (RFCA) for patients with symptomatic PVCs and IVTs originating from the vicinity of TA.MethodsCharacteristics of body surface electrocardiogram (ECG) and electrophysiologic recordings were analyzed in 35 patients with symptomatic PVCs/ IVTs originating from the vicinity of TA. RFCA was performed using pace mapping and activation mapping.ResultsAmong the 35 patients with PVCs/IVTs arising from the vicinity of TA, complete elimination of PVCs/IVTs could be achieved by RFCA in 32 patients (success rate 91.43%) during a median follow-up period of 21 months. PVCs/IVTs originating from the vicinity of TA had distinctive ECG characteristics that were useful for identifying the precise origin. An rS pattern was recorded in lead V1 in 93.1% of patients with PVCs/IVTs from the free wall of TA, vs 16.7% of patients with PVCs/IVTs from the septal TA, whereas a QS pattern in lead V1 occurred in 83.3% of patients with PVCs/IVTs from the septal TA vs 6.9% of patients with PVCs from the free wall of the TA. The precordial R wave transition occurred by lead V3 or earlier in all patients with PVCs/IVTs originating from the septal portion of the TA, as compared to transition beyond V3 in all patients with PVCs/IVTs from the free wall of the TA.ConclusionsRFCA is an effective curative therapy for symptomatic PVCs/IVTs originating from the vicinity of TA. There are specific characteristics in ECG and the ablation site could be located by ECG analysis.

BackgroundElevated heart rate is associated with increased cardiovascular morbidity. The selective If current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects by decreasing cardiac proinflammatory cytokines and inhibiting peroxidants and collagen accumulation in atherosclerosis or congestive heart failure. However, the effects of ivabradine in the setting of acute viral myocarditis and on the cytokines, oxidative stress and cardiomyocyte apoptosis have not been investigated.Methodology/Principal FindingsThe study was designed to compare the effects of ivabradine and carvedilol in acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of ivabradine and carvedilol (a nonselective β-adrenoceptor antagonist) on myocardial histopathological changes, cardiac function, plasma noradrenaline, cytokine levels, cardiomyocyte apoptosis, malondialdehyde and superoxide dismutase contents were studied. Both ivabradine and carvedilol similarly and significantly reduced heart rate, attenuated myocardial lesions and improved the impairment of left ventricular function. In addition, ivabradine treatment as well as carvedilol treatment showed significant effects on altered myocardial cytokines with a decrease in the amount of plasma noradrenaline. The increased myocardial MCP-1, IL-6, and TNF-α. in the infected mice was significantly attenuated in the ivabradine treatment group. Only carvedilol had significant anti-oxidative and anti-apoptoic effects in coxsackievirus B3-infected mice.Conclusions/SignificanceThese results show that the protective effects of heart rate reduction with ivabradine and carvedilol observed in the acute phase of coxsackievirus B3 murine myocarditis may be due not only to the heart rate reduction itself but also to the downregulation of inflammatory cytokines.

The aggressive immunological activity elicited by acute viral myocarditis contributes to a large amount of cardiomyocytes loss and poor prognosis of patients in clinic. Low‐intensity pulsed ultrasound ( LIPUS ), which is an effective treatment modality for osteoarthropathy, has been recently illustrated regulating the overactive inflammatory response in various diseases. Here, we aimed to investigate whether LIPUS could attenuate coxsackievirus B3 ( CVB 3) infection‐induced injury by coordinating the inflammatory response. Male BALB /c mice were inoculated intraperitoneally with CVB 3 to establish the model of acute viral myocarditis. LIPUS treatment was given on Day 1, Day 1, 3 and Day 1, 3, 5 post‐inoculation, respectively. All mice were followed up for 14 days. Day 1, 3, 5 LIPUS treatment significantly improved the survival rate, attenuated the ventricular dysfunction and ameliorated the cardiac histopathological injury of CVB 3‐infected mice. Western blotting analysis showed Day 1, 3, 5 LIPUS treatment decreased pro‐inflammatory cytokines, increased the activation of caveolin‐1 and suppressed p38 mitogen‐activated protein kinase ( MAPK ) and extracellular signal‐regulated kinase ( ERK ) signallings in heart tissue. RAW 264.7 cells were treated with lipopolysaccharides ( LPS ) to simulate the augmented inflammatory response in vivo. LIPUS treatment on RAW264.7 inhibited the expression of pro‐inflammatory cytokines, activated caveolin‐1 and suppressed p38 MAPK and ERK signallings. Transfecting RAW 264.7 with caveolin‐1 si RNA blunted the suppression of pro‐inflammatory cytokines and MAPK signallings by LIPUS treatment. Taken together, we demonstrated for the first time that LIPUS treatment attenuated the aggressive inflammatory response during acute viral myocarditis. The underlying mechanism may be activating caveolin‐1 and suppressing MAPK signallings.

Smoking is a major risk factor for atherosclerosis. In this study, we evaluated the effects of benzo[a]pyrene (BaP, a prominent component of tobacco smoke) on the function and pro-inflammatory response of human endothelial progenitor cells (EPCs). EPCs were isolated from umbilical cord blood and treated with different concentrations (10, 20 and 50 µmol/l) of BaP. The proliferation, migration, adhesion and angiogenesis of BaP-treated EPCs were evaluated using the cell counting kit-8 (CCK-8), Transwell assay, adhesion assay and in vitro tube formation assay, respectively. The activation of nuclear factor-κB (NF-κB) was evaluated by measuring the mRNA expression of NF-κB p65 and p50 by real-time RT-PCR and NF-κB translocation assay. Reactive oxygen species (ROS) production was determined by the reduction of fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). The results demonstrated that BaP treatment significantly inhibited the proliferation, migration, adhesion and angiogenesis of EPCs in vitro. In addition, BaP induced the release of interleukin (IL)-1β and tumor necrosis factor-α from these cells. Moreover, the exposure of EPCs to BaP induced ROS generation and the activation of NF-κB. Experiments with EPCs pre-treated with pyrrolidine dithiocarbamate, an inhibitor of NF-κB, revealed that the BaP-mediated inhibition of proliferation, migration, adhesion and angiogenesis of EPCs is mainly regulated by NF-κB. Thus, tobacco smoke may induce oxidant-mediated stress responses in EPCs and impair their function via the activation of the NF-κB pathway.

BackgroundWith chronic ischemia after myocardial infarction, the resulting scar tissue result in electrical and structural remodeling vulnerable to an arrhythmogenic substrate. The cholinergic anti‐inflammatory pathway elicited by vagal nerve via α7 nicotinic acetylcholine receptors (α7‐nAChR) can modulate local and systemic inflammatory responses. Here, we aimed to clarify a novel mechanism for the antiarrhythmogenic properties of vagal nerve during the ischemic cardiomyopathy (ICM).Methods and ResultsLeft anterior descending artery of adult male Sprague‐Dawley rats was ligated for 4 weeks to develop ICM. Western blot revealed that eliciting the cholinergic anti‐inflammatory pathway by nicotine treatment showed a significant reduction in the amounts of collagens, cytokines, and other inflammatory mediators in the left ventricular infarcted border zone via inhibited NF‐κB activation, whereas it increased the phosphorylated connexin 43. Vagotomy inhibited the anti‐inflammatory, anti‐fibrosis, and anti‐arrhythmogenic effect of nicotine administration. And immunohistochemistry confirmed that the nicotine administration‐induced increase of connexin 43 was located in intercellular junctions. Furthermore nicotine treatment suppressed NF‐κB activation in lipopolysaccharide‐stimulated RAW264.7 cells, and α‐bungarotoxin (an α7‐nAChR selective antagonist) partly inhibited the nicotine‐treatment effect. In addition, 4‐week nicotine administration slightly improved the cardiac function, increased cardiac parasympathetic tone, decreased the prolonged QTc, and decreased the arrhythmia score of programmed electric stimulation‐induced ventricular arrhythmia.ConclusionsEliciting the cholinergic anti‐inflammatory pathway exerts anti‐arrhythmogenic effects against ICM‐induced ventricular arrhythmia accompanied by downregulation of cytokines, downgenerating of collagens, decrease in sympathetic/parasympathetic ratio, and prevention of the loss of phosphorylated connexin 43 during ICM. Our findings may suggest a promising therapy for the generation of ICM‐induced ventricular arrhythmia by eliciting the cholinergic anti‐inflammatory pathway.