Electrical stimulation of cardiomyocytes activates mitochondrial matrix metalloproteinase causing electrical remodeling

Cardiac arrhythmias, instigated by mechanical and electrical remodeling, are associated with activation of extracellular matrix metalloproteinases (MMPs). However, the connection between intracellular MMPs activation and arrhythmogenesis is not well established. Previously, we determined localization of MMP in the mitochondria using confocal microscopy. We tested the hypothesis that electrical pacing induces the activation of mitochondrial MMP (mtMMP) and is associated with myocyte mechanical dysfunction. Myocytes were isolated and field stimulated at 1 and 4 Hz. Myocyte mechanics and calcium transient was studied using Ion-Optix system. Mitochondrial MMP-9 activation was evaluated using zymography. There was a 25% increase in 1 Hz and 40% increase in 4 Hz stimulation. We observed an increase in mtMMP activation with increase in electrical pacing compared to 0 Hz with a significant increase (p < 0.05, n = 3). Field stimulation at 4 Hz decreased cell re-lengthening. The levels of calcium transient were reduced with increase in contraction frequency. We conclude that electrical stimulation activates mtMMP-9 that is associated with myocyte mechanical dysfunction.     

Sex differences in expression and subcellular localization of heart rhythm determinant proteins

To evaluate sex differences in protein expression in the heart, we performed Western blot studies on a subset of Heart Rhythm Determinant (HRD) proteins. We examined key components of a variety of types of mechanical and electrical junctions including, connexin43, plakophilin-2, N-cadherin and plakoglobin, ankyrin-2 and actin. We describe novel findings in sex differences in cardiac protein expression and membrane localization. For most proteins examined, sex differences were significantly more pronounced in the membrane compartment than in overall expression. These studies extend our previous findings in microarray studies to demonstrate that sex differences in gene expression are likely to confer distinct functional properties on male and female myocardium.     

Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms

Resveratrol has been demonstrated to produce a variety of biological actions. Accumulating line of evidence supported the view that resveratrol may exert protective effect on the cardiovascular system. The aim of the study was to assess the antiarrhythmic profile as well as electrophysiological properties of resveratrol. We observe the antiarrhythmic effect of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia animal models. Resveratrol significantly and dose-dependently increased the doses of aconitine and ouabain required to induce the arrhythmia indexes. In coronary ligation induced rat arrhythmia model, resveratrol shortened duration of arrhythmia, decreased incidence of ventricular tachycardia and mortality. Electrophysiological experiment revealed that resveratrol could shorten APD through inhibition of ICa and selective enhancement of IKs without an effect on IKr.     

Baseline NT-Pro-BNP Levels and Arrhythmia Recurrence in Outpatients Undergoing Elective Cardioversion of Persistent Atrial Fibrillation: A Survival Analysis

Background

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Elective electrical cardioversion is often performed in patients with persistent AF to attempt sinus rhythm (SR) restoration. However, AF recurrences are frequent after successful cardioversion and several predictors have been identified.

Aim of the study

The present study was designed to prospectively analyse the correlation between NT-pro-BNP levels and AF recurrence in consecutive patients referred for electrical cardioversion of persistent atrial fibrillation.

Results

Forty consecutive patients referred for elective cardioversion of AF were enrolled in the study. Cardioversion restored sinus rhythm in 34/40 patients but 2 of them presented an early recurrence of AF before discharge. Patients were then followed for 6 months to assess AF recurrence. Cox regression analysis was performed using the parameters found predictive on univariate survival analysis (NT-pro-BNP quartiles, beta-blockers). The only independent predictor of AF recurrence on Cox-regression analysis was a level of NT-pro-BNP in the fourth quartile (HR 3.21 95%CI 1.26-8.14, p=0.014). On receiver operating curve (ROC) analysis, NT-pro-BNP levels above 1707 pg/ml had a specificity of 92% (and a sensitivity of 36%) in predicting atrial fibrillation recurrence by 6 months.

Conclusions

Baseline NT-pro-BNP levels are an independent predictor of AF recurrence at 6 months follow-up in candidates for elective direct current cardioversion.     

房颤大鼠模型心室重构与心肌细胞钙稳态和心律失常的关联

摘要 目的：探讨房颤大鼠模型心室重构与心肌细胞钙稳态和心律失常的关联性。方法：将雄性Wistar大鼠随机平分为两组,各组8只,模型组采用乙酞胆碱-氯化钙混合液尾静脉注射法建立房颤动物模型,对照组注射同剂量的生理盐水,记录两组心室重构、心肌细胞钙稳态、心律失常情况并进行相关性分析。结果：模型组建模第2周与第4周的左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）值都高于对照组（P<0.05）。模型组建模第2周与第4周的血清肌钙蛋白（cTnT）含量高于对照组（P<0.05）。模型组建模第2周与第4周心脏体外牵张性心律失常持续时间都高于对照组（P<0.05）。Pearson相关分析显示建模第2周与第4周的LVEDD、LVESD、cTnT与牵张性心律失常持续时间存在正相关（P<0.05）。结论：房颤大鼠伴随有心室重构与心肌细胞钙离子的大量释放,可增加牵张性心律失常持续时间,相关性分析结果表明：心室重构、心肌细胞钙稳态和心律失常存在显著正相关性。     

心梗大鼠离体心脏的动作电位和不应期电生理研究

目的对比观察正常大鼠和心梗大鼠离体心脏动作电位和有效不应期的特点。方法用离体灌流吸附电极记录单向动作电位,常规电生理方法测量最大动作电位幅度(APA)、复极90%(MAP90)、复极50%(MAP50)、复极20%(MAP20)、有效不应期(ERP)。结果(1)和正常大鼠相比,心梗大鼠离体心脏左心房电生理参数MAP90(56.3±2.7vs.64.5±8.7,P<0.05)显著延长,ERP MAP90(0.89±0.2vs.0.78±0.3,P<0.05)减小,基础周期为250ms;右心室的电生理参数MAP90(67.6±14.1vs.134.1±26.7,P<0.001),ERP(55.0±3.53vs.69.0±8.9,P<0.05)明显延长,ERP MAP90(0.79±0.1vs.0.60±0.1,P<0.05)减小,基础周期为250ms;左心室的电生理参数MAP90(87.2±15.7vs.168.8±31.2,P<0.001)也呈显著延长,ERP(59.0±4.2vs.90.0±17.7,P<0.001),ERP MAP90(0.65±0.081vs.0.54±0.090,P<0.05)呈显著减小基础周期为250ms;(2)与正常大鼠相比,心梗大鼠的MAP90离散度[(LVMAP90-RVMAP90)(17.0±6.5vs.51.4±28.7,P<0.001)]、ERP离散度[(LVERP-RVERP)(4.0±2.2vs.20.0±7.9)P<0.001]显著增加,基础周期为250ms。结论心梗大鼠心脏不同部位的MAP的复极时间都显著性延长,MAP90和ERP离散度增加,这些电生理特点是促进折返形成、造成心律失常的主要原因。     

Failure-free survival of the Riata implantable cardioverter-defibrillator lead after a very long-term follow-up

AimsRiata^® implantable cardioverter-defibrillator (ICD) leads from St. Jude Medical are prone to malfunction. This study aimed to describe the rate of this lead's malfunction in a very long-term follow-up.MethodsThis single-centre observational study included 50 patients who received a Riata 7Fr dual-coil lead between 2003 and 2008. Follow-up was conducted both in person and remotely, and analysed at 8-month intervals. We evaluated the rates of cable externalization (CE), electrical failure (EF), and the interaction of these two complications. Structural lead failure was defined as radiographic CE. Oversensing of non-cardiac signal or sudden changes in impedance, sensing, or pacing thresholds constituted EF.ResultsDuring a mean follow-up of 10.2 ± 2.9 years, 16 patients (32%) died. We observed lead malfunction in 13 patients (26%): three (23%) due to CE, six (46%) to EF and four (31%) to both complications. Of the malfunctioning leads, 77% failed after seven years of follow-up. The incidence rate (IR) of overall malfunction per 100 patients per year was 0.9 during the first seven years post-implantation, increased to 7.0 after the 7th year and more than doubled (to 16.7) after 10 years. Beyond seven years post-implantation, IR per 100 patient-years increased in both EF and CE (from 0.6 to 5.6 vs. 0.3 to 4.2, respectively). Presence of CE was associated with a 4-fold increase in the proportion of EF.ConclusionThe incidence of Riata ICD lead malfunction, both for EF and CE, increased dramatically after seven years and then more than doubled after 10 years post-implantation.