This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen–glucose deprivation and reoxygenation (OGD/R) model ...and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.
The relationship between triglyceride-glucose (TyG) index, an emerging marker of insulin resistance, and the risk of incident heart failure (HF) was unclear. This study thus aimed to investigate this ...relationship.
Subjects without prevalent cardiovascular diseases from the prospective Kailuan cohort (recruited during 2006-2007) and a retrospective cohort of family medicine patients from Hong Kong (recruited during 2000-2003) were followed up until December 31st, 2019 for the outcome of incident HF. Separate adjusted hazard ratios (aHRs) summarizing the relationship between TyG index and HF risk in the two cohorts were combined using a random-effect meta-analysis. Additionally, a two-sample Mendelian randomization (MR) of published genome-wide association study data was performed to assess the causality of observed associations.
In total, 95,996 and 19,345 subjects from the Kailuan and Hong Kong cohorts were analyzed, respectively, with 2,726 cases of incident HF in the former and 1,709 in the latter. Subjects in the highest quartile of TyG index had the highest risk of incident HF in both cohorts (Kailuan: aHR 1.23 (95% confidence interval: 1.09-1.39), PTrend <0.001; Hong Kong: aHR 1.21 (1.04-1.40), PTrend =0.007; both compared with the lowest quartile). Meta-analysis showed similar results (highest versus lowest quartile: HR 1.22 (1.11-1.34), P < 0.001). Findings from MR analysis, which included 47,309 cases and 930,014 controls, supported a causal relationship between higher TyG index and increased risk of HF (odds ratio 1.27 (1.15-1.40), P < 0.001).
A higher TyG index is an independent and causal risk factor for incident HF in the general population.
URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR-TNRC-11,001,489.
Background
Ablation index (AI), a novel lesion quality marker, includes contact force, time, and power of radiofrequency (RF) application, but not regional variation in wall thickness within the wide ...antral catheter ablation (WACA) circle. This study explored the relationships among AI target value, atrial wall thickness, and gap formation within the WACA circle in patients with paroxysmal atrial fibrillation (PAF).
Methods
We evaluated 102 consecutive patients (mean age, 65 ± 9 years) with PAF who underwent AI‐guided WACA for ipsilateral pulmonary vein isolation (PVI). Each WACA circle was subdivided into eight segments, and overall 7143 RF applications were delivered, including 125 gaps in PVI ablation lines. For each RF tag within the ablation circle, we collected data on ablation lesion depth surrogates (time of application, delivery power, impedance drop, average contact force, force‐time integral FTI, and AI) and left atrial wall thickness measured by multidetector computer tomography scanning.
Results
The anterior and roof walls were the thickest segments of the ablation circle, in which 85.8% of gaps concentrated, while the posterior and inferior walls were the thinnest. Gap formation was significantly associated with FTI, AI, wall thickness, FTI/wall thickness, and AI/wall thickness. AI/wall thickness had the highest predictive value for gap formation, with a cutoff of 195.6 au/mm for effective ablation.
Conclusions
In AI‐guided PVI of PAF, AI/wall thickness by normalizing myocardial thickness variation along the WACA circle was a strong predictor of gap formation, with a target of 195.6 au/mm appearing suitable for effective ablation.
Abnormal cardiac fibrosis is the main pathological change of post-myocardial infarction (MI) heart failure. Although the E3 ubiquitin ligase FBXL8 is a key regulator in the cell cycle, cell ...proliferation, and inflammation, its role in post-MI ventricular fibrosis and heart failure remains unknown. FBXL8 was primarily expressed in cardiac fibroblasts (CFs) and remarkably decreased in CFs treated by TGFβ and heart subjected to MI. The echocardiography and histology data suggested that adeno-associated viruses (AAV9)-mediated FBXL8 overexpression had improved cardiac function and ameliorated post-MI cardiac fibrosis. In vitro, FBXL8 overexpression prevented TGFβ-induced proliferation, migration, contraction, and collagen secretion in CFs, while knockdown of FBXL8 demonstrated opposite effects. Mechanistically, FBXL8 interacted with Snail1 to promote Snail1 degradation through the ubiquitin-proteasome system and decreased the activation of RhoA. Moreover, the FBXL8ΔC3 binding domain was indispensable for Snail1 interaction and degradation. Ectopic Snail1 expression partly abolished the effects mediated by FBXL8 overexpression in CFs treated by TGFβ. These results characterized the role of FBXL8 in regulating the ubiquitin-mediated degradation of Snail1 and revealed the underlying molecular mechanism of how MI up-regulated the myofibroblasts differentiation-inducer Snail1 and suggested that FBXL8 may be a potential curative target for improving post-MI cardiac function.
A 23‐year‐old woman with palpitations for 9 years was referred for catheter ablation. ECG showed an irregular narrow complex tachycardia with alternating and gradually changing QRS morphologies after ...alternating and changing RR intervals, with a clear pattern of 2 alternating QRS complexes. An electrophysiology study was performed and confirmed that the mechanism of tachycardia was an automatic left‐side His‐Purkinje system (HPS) ventricular tachycardia. The gradually changing type‐2 QRS complexes was the conduction delayed in the left anterior fascicle due to the short RR interval or the short left‐side HH interval. Nine months after the index electrophysiology study, the patient encounter a progressive of heart failure with increased heart rate to 130‐150 bpm during rest. Radiofrequency ablation was performed at the upper‐septum for eliminating the tachycardia and resulted in complete atrioventricular block. A permanent pacemaker with left bundle branch pacing was implanted. Twelve months after the ablation, the enlarged heart shrink to normal with normal left ventricular ejection fraction. In conclusion, careful interpretation of the ECG can identify the sinus P waves followed by irregular narrow complexes, thus avoiding misdiagnosis and unnecessary treatment. Unifocal HPS tachycardia could present with alternating and gradually changing narrow QRS complexes tachycardia and lead to tachycardia cardiomyopathy. Electrophysiology study and catheter ablation were useful for the diagnosis and treatment of HPS tachycardia but with high risk of atrioventricular block. However, successfully elimination the tachycardia would resolve and reverse the enlarged heart and deteriorative heart function.
Renal denervation (RD) was reported to reduce the susceptibility of atrial fibrillation (AF), but the underlying mechanism has not been well understood. This study was performed to investigate the ...effect of RD on the inducibility of AF in a rabbit model for atrial fibrosis and to explore the potential mechanisms. Thirty-five rabbits were randomly assigned into sham-operated group (n = 12), abdominal aortic constriction (AAC) group (n = 12) and AAC with RD (AAC-RD) group (n = 11). The incidence of AF induced by burst pacing in atriums was determined. Blood was collected to measure the levels of rennin, angiotensin II and aldosterone. Atrial samples were preserved to evaluate protein and gene expression of collagen, connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1). Our data suggested cardiac structure remodeling and atrial fibrosis were successfully induced by AAC. Compared with the AAC group, the AAC-RD rabbits had smaller ascending aortic diameter and left ventricular end-systolic diameter. For burst pacing at the left atrium (LA), AF was induced in two of the 12 rabbits in the sham-operated group, 10 of the 12 rabbits in the AAC group, and 2 of the 11 rabbits in the AAC-RD group, with great difference among the three groups (P = 0.001). The percentage of LA burst stimulations with induced AF achieved 47.2% in the AAC group, which was higher than those in both the AAC-RD (12.1%) and the Sham-operated (5.6%) groups. Significantly increasing intercellular space in the AAC group (P<0.001) compared with the sham-operated rabbits. RD clearly decreased the volume fraction of collagen in LA and right atrium compared with that of the AAC group (P< 0.01). AAC-induced elevation of collagen I, CTGF and TGF-β1 was suppressed by RD. In conclusion, RD suppressed the inducibility of AF in a rabbit model for pressure associated atrial fibrosis, potentially by modulating renin-angiotensin-aldosterone system and decreasing pro-fibrotic factors.
The present study aimed to evaluate the importance of cyanidin 3-glucoside (C3G) of diabetic cardiomyopathy in diabetic rats. The rats were induced with diabetic using streptozotocin and total ...triglyceride (TG) and total cholesterol (TC) were determined. The range of myocardial enzymes such as aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LD) were also estimated, further, the Immuno histochemical analysis and western blot investigation were determined for the actual activity of C3G. Results indicated that the marker enzymes such as CK, LD and AST were significantly (P<0.05) increased in STZ administered rats (DM group), while the levels of these elevated marker enzymes of cardiac injury significantly (P<0.05) declined in the DM+C3G group, as compared to the diabetic group of rats. Additionally, a decrease in the level of TNF-alpha and interleukin-6, was noticed in the C3G treated group as compared to diabetic group. Finally, blotting analysis clearly confirmed that theC3G treatment resulted to higher level response of Bcl-2 and lower level response of caspase-3 and BAX. In conclusion, C3G a natural antioxidant may prevent cardiovascular complications by ameliorating oxidative damage, inflammation, metabolic dysfunctions and apoptosis pathways in type 2 diabetes.
Aims
Pocket hematoma is a common complication associated with cardiac device implantation, but there are limited strategies to deal with this problem. We aimed to evaluate the effectiveness of ...sub-pocket small-hole drainage (SSD) as a new way to manage severe pocket hematoma.
Methods
A total of 11 patients with severe pocket hematoma were selected for this case series study. The SSD procedure was performed and wound healing was monitored.
Results
The SSD procedure was successfully performed on all 11 patients. The time window for SSD was 10–14 days (mean 12.0 ± 1.3 days) after cardiac device implantation. On average, 18.3 ± 2.3 ml of hematoma was drained , with a mean procedural time of 21.3 ± 2.6 min. The patients were followed up for 4–12 months and all pockets healed well, without any complications such as pocket infection, bleeding, device exposure, and electrode fracture.
Conclusion
Sub-pocket small-hole drainage is an alternative approach for dealing with severe pocket hematoma after cardiac device implantation.
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