ABSTRACT
Seldom are reports of phase 4 block or bradycardia-dependent conduction block in atrial tissue found in the literature. Here, we describe the case of a patient with sick sinus syndrome with Torsade de Pointes who, following the implantation of a double-chamber implantable cardioverter defibrillator, developed intra-atrial bradycardia-dependent conduction block. The patient's optimal pacing parameters were achieved by raising the rate.
ABSTRACT
The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps-/- mice) to investigate the role of FDPS in cardiac homeostasis. Cardiac function was assessed using echocardiography. Left ventricles were examined and tested for histological and molecular markers of cardiac remodeling. Our results showed that FDPS levels were downregulated in samples from patients with cardiomyopathy. Furthermore, c-Fdps-/- mice exhibited cardiac remodeling and dysfunction. This dysfunction was associated with abnormal activation of Ras and Rheb, which may be due to the accumulation of geranyl pyrophosphate. Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways. Moreover, administration of farnesyltransferase inhibitors attenuated cardiac remodeling and dysfunction in c-Fdps-/- mice. These results indicate that FDPS plays an important role in cardiac homeostasis. Deletion of FDPS stimulates the downstream mTOR and ERK signaling pathways, resulting in cardiac remodeling and dysfunction. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Cardiomyopathies/pathology , GTP-Binding Proteins/metabolism , Geranyltranstransferase/metabolism , Ventricular Remodeling/physiology , Animals , Humans , MiceABSTRACT
ABSTRACT: Cardiotoxicity has been well documented as a side effect of cisplatin (CDDP) treatment. The inflammatory response plays a crucial role in the pathological process of CDDP-induced cardiotoxicity. Wogonin is a natural flavonoid compound that possesses cardioprotective and anti-inflammatory qualities. Knowledge of the pharmacological effect and mechanism of wogonin could reveal an efficient way to identify therapeutic strategies. In this study, the potential of wogonin to antagonize CDDP-induced cardiotoxicity was evaluated in C57BL/6 mice in vivo and in H9c2 cells in vitro. The results showed that wogonin protected against CDDP-induced cardiac dysfunction, myocardial injury, and pyroptosis in vivo. Using a Gasdermin D expression plasmid, we revealed that wogonin dramatically reduced CDDP-induced pyroptosis by modulating the Gasdermin D protein in H9c2 cells. In conclusion, wogonin has great potential in attenuating CDDP-induced cardiotoxicity. In addition, greater emphasis should be placed on the antipyroptotic effects of wogonin for the treatment of other diseases.
Subject(s)
Flavanones/pharmacology , Heart Diseases/prevention & control , Myocytes, Cardiac/drug effects , Phosphate-Binding Proteins/antagonists & inhibitors , Pore Forming Cytotoxic Proteins/antagonists & inhibitors , Protective Agents/pharmacology , Pyroptosis/drug effects , Animals , Cardiotoxicity , Cell Line , Cisplatin , Disease Models, Animal , Heart Diseases/chemically induced , Heart Diseases/metabolism , Heart Diseases/pathology , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Male , Mice, Inbred C57BL , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Phosphate-Binding Proteins/metabolism , Pore Forming Cytotoxic Proteins/metabolism , Rats , Signal TransductionABSTRACT
A 26-year-old man diagnosed with nephrotic syndrome (NS) 2 years previously presented with chest pain. An electrocardiogram (ECG) performed at a local hospital showed ST-elevation in chest leads. Cardiac troponin-I was significantly positive. Echocardiography revealed mild regional wall-motion abnormalities in the heart apex. Seven days later, angiography (CAG) revealed a thrombus in the left anterior descending branch (LAD). Tirofiban was injected into the LAD for thromboclasis. ECG after CAG showed the ST-segment was much lower than before. The diagnosis after CAG was ST-segment elevation myocardial infarction (MI) and thrombogenesis in the LAD. He continued to receive antiplatelet and anticoagulation medication and atorvastatin after CAG, and was discharged 3 days later. MI is very rare in young males, but the incidence of MI is 8 times higher than normal in patients with NS. For young patients with MI, clinicians should pay more attention to the history of previous diseases with high risk of thromboembolism and they should actively promote prevention and the treatment of renal disease patients to reduce the incidence of complications of thromboembolism.
Subject(s)
Myocardial Infarction/etiology , Nephrotic Syndrome/complications , Adult , Electrocardiography , Humans , Male , Myocardial Infarction/diagnosisABSTRACT
BACKGROUNDS: Segmental and circumferential pulmonary vein isolations (SPVI and CPVI) have been demonstrated to be effective therapies for paroxysmal atrial fibrillation (PAF). PVI is well established as the endpoint of different ablation techniques, whereas it may not completely account for the long-term success. METHODS: 181 drug-refractory symptomatic PAF patients were referred for segmental or circumferential PVI (SPVI = 67; CPVI = 114). Heart rate variability (HRV) was assessed before and after the final ablation. RESULTS: After following up for 62.23 ± 12.75 months, patients underwent 1.41 ± 0.68 procedures in average, and the success rates in SPVI and CPVI groups were comparable. 119 patients were free from AF recurrence (SPVI-S, n = 43; CPVI-S, n = 76). 56 patients had recurrent episodes (SPVI-R, n = 21; CPVI-R, n = 35). Either ablation technique decreased HRV significantly. Postablation SDNN and rMSSD were significantly lower in SPVI-S and CPVI-S subgroups than in SPVI-R and CPVI-R subgroups (SPVI-S versus SPVI-R: SDNN 91.8 ± 32.6 versus 111.5 ± 36.2 ms, rMSSD 47.4 ± 32.3 versus 55.2 ± 35.2 ms; CPVI-S versus CPVI-R: SDNN 83.0 ± 35.6 versus 101.0 ± 40.7 ms, rMSSD 41.1 ± 22.9 versus 59.2 ± 44.8 ms; all P < 0.05). Attenuation of SDNN and rMSSD remained for 12 months in SPVI-S and CPVI-S subgroups, whereas it recovered earlier in SPVI-R and CPVI-R subgroups. Multivariate logistic regression analysis identified SDNN as the only predictor of long-term success. CONCLUSIONS: Beyond PVI, denervation may be a common mechanism underlying different ablation strategies for PAF.
Subject(s)
Atrial Fibrillation/pathology , Atrial Fibrillation/surgery , Denervation/methods , Pulmonary Veins/surgery , Adult , Atrial Fibrillation/physiopathology , Catheter Ablation , Electrocardiography, Ambulatory , Female , Heart Rate , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pulmonary Veins/physiopathology , Recurrence , Treatment OutcomeABSTRACT
BACKGROUND: Cardiac hypertrophy is one of the initial disorders of the cardiovascular system and can induce heart failure. Oxidative stress is an important pathophysiological mechanism of cardiac hypertrophy. Wogonin (Wog), an important flavonoid derived from the root of Scutellaria baicalensis Georgi, is known to possess antioxidant properties. METHODS: An in vitro model of cardiac hypertrophy was established by stimulating H9C2 cells and neonatal rat cardiomyocytes (NRCMs) with angiotensin II (AngII). The indices related to myocardial hypertrophy and oxidative stress were detected. An in vivo model of cardiac hypertrophy was induced by transverse aortic constriction (TAC) in C57BL/6 mice. Cardiac function was monitored by chest echocardiography, and the hypertrophy index was measured. The mice were then sacrificed for histological assays, with mRNA and protein detection. To further explore the role of nuclear factor- (erythroid-derived 2-) like 2 (Nrf-2) in regulating the antioxidant effects of Wog in cardiac hypertrophy, siRNA analysis was conducted. RESULTS: Our results showed that Wog significantly ameliorated AngII-induced cardiomyocyte hypertrophy by inhibiting oxidative stress in H9C2 cells and NRCMs. In addition, Wog treatment prevented oxidative stress and improved cardiac hypertrophy in mice that underwent TAC. Using gene-specific siRNA for Nrf-2, we discovered that these antioxidative effects of Wog are mediated through Nrf-2 induction. CONCLUSIONS: Our results provide further evidence for the potential use of Wog as an antioxidative agent for treatment of cardiac hypertrophy, and Nrf-2 might serve as a therapeutic target in the treatment of cardiac hypertrophy.
Subject(s)
Antioxidants , Flavanones , Myocardium , Animals , Antioxidants/pharmacology , Cardiomegaly/drug therapy , Cardiomegaly/prevention & control , Flavanones/pharmacology , Mice , Mice, Inbred C57BL , Myocytes, Cardiac , RatsABSTRACT
Cardiac hypertrophy is a current, major, global health challenge. Oxidative stress is an important mechanism that contributes to the pathogenesis of cardiac hypertrophy. Schisandra chinensis polysaccharides (SCP), the primary active constituent in Schisandra chinensis, have antioxidative properties. Here, we investigated the role played by SCP in a cardiac hypertrophy model mouse induced by transverse aortic constriction (TAC). We found that SCP treatment improved cardiac function by inhibiting myocardial hypertrophy and oxidative stress. Angiotensin II was used to induce cardiomyocyte hypertrophy and oxidative stress in vitro. We discovered that the antioxidant effects of SCP were mediated through the regulation of the thioredoxin-interacting protein (TXNIP)/Thioredoxin-1 (Trx-1) pathway. Using molecular docking, we found that SCP binds to Arg207, Ser169, Lys166, Lys286 and Ser285 in TXNIP through hydrogen bonds. TXNIP is an endogenous inhibitor of Trx-1, and the binding SCP with TXNIP may restrict or interfere with the binding between TXNIP and Trx-1, resulting in Trx-1 activation. In conclusion, our findings demonstrated that the potential use of SCP as a TXNIP inhibitor to attenuate oxidative stress, suggesting that TXNIP might represent a potential therapeutic target for the treatment of cardiac hypertrophy.
Subject(s)
Cardiomegaly/prevention & control , Oxidative Stress/drug effects , Polysaccharides/pharmacology , Schisandra/metabolism , Thioredoxins/metabolism , Angiotensin II/pharmacology , Animals , Antioxidants/physiology , Cardiomegaly/metabolism , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Molecular Docking Simulation/methods , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , RatsABSTRACT
This work aimed to study the diagnostic value of dynamic electrocardiogram (ECG) based on P wave detection algorithm for arrhythmia after hepatectomy in patients with primary liver cancer, and to compare the therapeutic effect of different doses of Betaloc. P wave detection algorithm was introduced for ECG automatic detection and analysis, which can be used for early diagnosis of arrhythmia. Sixty patients with arrhythmia after hepatectomy for primary liver cancer were selected as the research objects. They were randomly divided into control group, SD group, MD group, and HD group, with 15 cases in each group. No Betaloc, low-dose (≤47.5 mg), medium-dose (47.5-95 mg), and high-dose (142.5-190 mg) Betaloc were used for treatment. As a result, P wave detection algorithms can mark P waves that may be submerged in strong interference. P waves from arrhythmia database were used to verify the performance of the proposed algorithm. The prediction precision (Pp) of ventricular arrhythmia and atrial arrhythmia was 98.53% and 98.76%, respectively. Systolic blood pressure (117.35 ± 7.33, 126.44 ± 9.38, and 116.02 ± 8.2) mmHg in SD group, MD group, and HD group was significantly lower than that in control group (140.3 ± 7.21) mmHg after two weeks of treatment. Moreover, those of SD group and HD group were significantly lower than MD group (P < 0.05). The effective rate of cardiac function improvement in SD group (72.35 ± 1.21%) was significantly higher than that in control group, MD group, and HD group (38.2 ± 0.98%, 65.12 ± 1.33%, and 60.43 ± 1.25%; P < 0.05). In short, dynamic ECG based on P wave detection algorithm had high diagnostic value for arrhythmia after hepatectomy in patients with primary liver cancer. It was safe and effective for patients to choose small dose of Betaloc.
Subject(s)
Electrocardiography , Metoprolol , Algorithms , Arrhythmias, Cardiac/diagnosis , Databases, Factual , HumansABSTRACT
BACKGROUND: Atrial electrical remodeling (AER) is the underlying mechanism of atrial fibrillation (AF). The present study investigated the impact of epicardial fat pad (FP) ablation on acute AER (AAER) and inducibility of AF. METHODS AND RESULTS: AAER was performed in 28 mongrel dogs through 4-h rapid atrial pacing (RAP). Before RAP, 14 dogs (ablation group) underwent FP ablation, and the other 14 (control group) underwent a sham procedure. The atrial effective refractory period (ERP) and vulnerability window (VW) of AF were measured with and without bilateral cervical vagosympathetic nerve stimulation (VNS) at the high right atrium, ostium of the coronary sinus (CS) and distal CS before and after every hour of RAP. In the control group, ERP was markedly shortened in the first 2 h of RAP and then stabilized. AF was only slightly induced. After RAP, the time course of ERP with and without VNS was similar. VNS significantly shortened ERP and increased VW before and after RAP. In the ablation group, ERP was significantly prolonged after FP ablation. Moreover, neither VNS nor RAP shortened the ERP or increased the VW. AF could not be induced (VW=0). CONCLUSIONS: RAP resulted in AAER, which may be mediated and aggravated by autonomic activity. Epicardial FP ablation generated denervation, which not only abolishes AF inducibility but also prevents RAP-mediated AAER.
Subject(s)
Atrial Fibrillation/physiopathology , Catheter Ablation , Pericardium/physiopathology , Animals , Atrial Fibrillation/etiology , Atrial Fibrillation/prevention & control , Dogs , Female , Male , Time FactorsABSTRACT
OBJECTIVE: High short-term successful rate was reported for catheter ablation in patients with paroxysmal atrial fibrillation (AF), we analyzed the long-term outcome (success rate, anticoagulation therapy and embolism event, anti-arrhythmic therapy and death post procedure) of catheter ablation for paroxysmal AF in this study. METHODS: From January 2000 to December 2004, 106 consecutive patients with drug-refractory paroxysmal AF underwent catheter ablation and were followed-up for (60.7 + or - 11.8) months. Segmental pulmonary vein isolation (SPVI) was routinely performed by radiofrequency energy under the guidance of circular mapping catheter. The patients were followed up with 24 h-holter, ECG, telephone or letter. Data on recurrence of AF, the anticoagulation medication and the incidence of embolism, anti-arrhythmic therapy were obtained. RESULTS: There were 9 patients lost to follow up. In the remaining 97 patients [65 males, (54.8 + or - 11.2) years old], 3 cases died from cancer, sinus rhythm was maintained in 68 patients (Group S, 72.3%) and AF recurrence evidenced in 26 patients (Group R, 27.7%). In Group S, 56 patients (82.4%) discontinued anticoagulation medication, and 12 patients continued to take aspirin. There was no embolism event in Group S during follow-up. In Group R, 1 patient continued to take warfarin; 11 patients continued to take aspirin and 2 patients suffered from cerebral embolism. Anticoagulation medication was discontinued in 14 patients (53.8%) and 1 patient suffered form cerebral embolism. The incidence of embolism event in Group R is significantly higher than in Group S (P < 0.01). More patients discontinued anti-arrhythmic medication in Group S than in Group R (80.9% vs. 56.0%, P < 0.05). CONCLUSION: Catheter ablation is associated with satisfactory long-term success rate, reduced anti-arrhythmia medication, improved quality of life in patients with paroxysmal AF.
Subject(s)
Atrial Fibrillation/therapy , Catheter Ablation , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
BACKGROUND: Ablation of complex fractionated atrial electrograms (CFAE) is an important adjunctive therapy in atrial fibrillation (AF). The present study was to elucidate the substrate underlying CFAE. METHODS: Nine adult mongrel dogs were involved in the present study. AF was induced through rapid atrial pacing with vagosympathetic nerve stimulation. CFAE was recorded during AF. Ablation was performed at CFAE sites. Based on the location of the ablation scar, the atrial specimens were divided into CFAE and non-CFAE sites. Serial sections of the atrium were stained respectively with hematoxylin-eosin (HE) and the general neural marker protein gene product 9.5 (PGP9.5). We compared the characteristics of the myocardium and the ganglionated plexus (GPs) distribution between the CFAE and non-CFAE sites. RESULTS: The myocardium of non-CFAE sites was well-organized with little intercellular substance. However, the myocardium in the CFAE site was disorganized with more interstitial tissue ((61.7 ± 24.3)% vs. (34.1 ± 9.2)%, P < 0.01). GPs in the CFAE site were more abundant than in non-CFAE sites ((34.45 ± 37.46) bundles/cm(2) vs. (6.73 ± 8.22) bundles/cm(2), P < 0.01). CONCLUSION: The heterogeneity of the myocardium and GPs distribution may account for the substrate of CFAE and serve as a potential target of ablation.