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@#Objective To evaluate the efficacy of hybrid ablation through compared with thoracoscopic epicardial ablation. Methods In this study, 108 patients with all long-standing persistent atrial fibrillation (LSPAF) received thoracoscopic epicardial ablation (TEA) after enrollment. There were 82 males and 26 females at age of 56.5±9.4 years. After blanking-period, patients off antiarrhythmic therapy with sinus rhythm were divided into a hybrid ablation (HA) group (50 patients) and a TEA group (58 patients). Only patients in the HA group received catheter ablation after randomization subsequently. In at least two-year observation period, cardiovascular risk factors were observed in all groups’ patients. Results The mean follow-up duration was 17.3-41.8 (26.9±6.1) months and there was no significant difference between two groups [8.2-40.6 (27.5±5.7) months in the HA group and 17.3-41.8 (26.4±6.7) months in the TEA group]. The off antiarrhythmic agents (AADs) sinus rhythm rate was significantly higher in the HA group than that in the TEA group at the time of postoperative 6, 12, 24 and 36 months ［96.0%, 90.0%, 83.7%, 83.7% versus 79.3%, 75.9%, 67.3%, 63.1%, HR=0.415 (95%CI 0.206-0.923)]. Conclusion We can conclude that the efficacy of two-staged hybrid ablation for LSPAF is superior to thoracoscopic epicardial ablation alone. Patients can obtain benefit from a supplemental radiofrequency catheter ablation after blanking-period of surgical ablation, instead of those without a supplemental ablation.
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Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca²⁺ homeostasis. The store-operated calcium (SOC) channel is the primary Ca²⁺ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca²⁺ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca²⁺ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.
Subject(s)
Blotting, Western , Calcium , Endoplasmic Reticulum , Endoplasmic Reticulum Stress , Endothelial Cells , Homeostasis , Human Umbilical Vein Endothelial Cells , Tunicamycin , Unfolded Protein ResponseABSTRACT
Objective To analyze the clinical characteristics and follow-up data of catheter ablation of recurrent atrial tachycardias (ATs) after Mini-Maze surgery,and to explore prognostic factors for recurrence.Methods 59 patients in Guangdong General Hospital with ATs post Mini-Maze and concomitant open-heart surgery from April.2010 to June.2015 were included.According to high density precise mapping,activation mapping,voltage mapping and entrainment mapping,they underwent electrophysiological study and ablation which was guided by three-dimensional mapping system.All patients were followed up regularly.We explored the prognostic factors for recurrence by the Cox regression analysis.Results There were 88 types of ATs being mappedwith mean (1.49 ± 0.75) types of ATs identified per case.Most ATs were macro-reentry ATs(67/88,76.1％)and focal ATs (20/88,22.7％),respectively.56 patients (94.9％) achieved immediate ablation success.In a mean follow-up of (30.8 ± 17.7) months,recurrences were observed in 12 patients after the first time catheter ablation.Recurrent time was 3.5 (1.3,12.0) months and the overall ablation success rate was 74.6％ (44/59).6 patients received second ablation and the achievement of freedom from arrhythmias reached 79.7％ (47/59).Multivariate analysis showed that the LA diameter was the independent predictor for recurrence (HR 1.108,95％ CI 1.002 to 1.226,P =0.045).Conclusion Catheter ablation of ATs post Mini-Maze with concomitant surgery is save and feasible.LA diameter is the independent predictor for recurrence.
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AIM:Increasing evidence indicates that inflammation contributes to the initiation and perpetuation of atrial fibrillation ( AF) .Al-though tumor necrosis factor ( TNF)-αlevels are increased in patients with AF , the role of TNF-αin the pathogenesis of AF remains unclear.Recent research has revealed that T-type Ca2+currents ( ICa,T ) play an important role in the pathogenesis of AF .METH-ODS:In this study , we used the whole-cell voltage-clamp technique and biochemical assays to explore the role of TNF-αin the regula-tion of ICa,T in atrial myocytes.RESULTS:We found that compared with sinus rhythm (SR) controls, T-type calcium channel (TCC) subunit mRNA levels were decreased , while TNF-αexpression levels were increased , in human atrial tissue from patients with AF .In murine atrial myocyte HL-1 cells, after cultured for 24 h, 12.5, 25 and 50 μg/L TNF-αsignificantly reduced the protein expression levels of the TCC α1G subunit in a concentration-dependent manner .The peak current was reduced by the application of 12.5 or 25μg/L TNF-αin a concentration-dependent manner [from ( -15.08 ±1.11) pA/pF in controls to ( -11.89 ±0.83) pA/pF and (-8.54 ±1.55) pA/pF in 12.5 and 25 μg/L TNF-αgroups, respectively].TNF-αapplication also inhibited voltage-dependent inactivation of ICa,T shifted the inactivation curve to the left .CONCLUSION:These results suggest that TNF-αis involved in the path-ogenesis of AF, probably via decreasing ICa,T function in atrium-derived myocytes through impaired channel function and down -regula-tion of channel protein expression .This pathway thus represents a potential pathogenic mechanism in AF .
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AIM:To investigate whether the association of connexin 43 ( Cx43 ) and L-type calcium channel involved in the pathogenesis of atrial fibrillation ( AF) .METHODS:The biochemical assays and whole-cell patch-clamp technique were used to study the expression of Cx43 in human atrial tissue.The co-localization of Cx43 and L-type calcium channel, and the regulation of L-type calcium current in atrial myocytes were investigated.RESULTS:The expression of Cx43 at mRNA and protein levels was decreased in human atrial tissues of AF patients.In cultured atrium-derived myocytes ( HL-1 cells) , knockdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channelα1c subunit, as well as L-type calcium current.Co-localization of Cx43 with L-type calcium channel α1c subunit in mouse atrial myocytes was observed.CONCLUSION:The decrease in Cx43 is involved in the pathogenesis of AF, probably through reducing the L-type calcium current in atrial myoctyes by co-localization with L-type calcium channel, thus representing the potential pathogenesis in atrial fibrillation.
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OBJECTlVE To investigate the mechanism of verapamiI in the treatment of type 2 Iong QT syndrome(LQT2)using a rabbit Ieft ventricuIar myocardiaI wedge preparation. METHODS E-4031 (0.5 μmoI·L-1 )was used to induce the LQT2 modeI after rabbit Ieft ventricuIar wedge preparations were equiIibrated for 1 h,and verapamiI(0.5,1.0 and 2.5 μmoI·L-1 ,respectiveIy)was perfused in different groups. Data were coIIected for a period of 30 min starting 30 min after adding the respective drug. Transmembrane action potentiaIs of endocardiaI and epicardiaI myocardium were recorded simuItaneous-Iy at a basic cycIe Iength of 2000 ms(S1S1)together with a transmuraI ECG. The effect of verapamiI (0.5,1.0 and 2.5 μmoI·L-1 )on action potentiaI duration at 90% repoIarization(APD90 ),QT intervaI, transmuraI dispersion of repoIarization(TDR)and the deveIopment of earIy afterdepoIarization(EAD) and torsades de pointes(TdP)were evaIuated in the LQT2 myocardiaI wedge modeI. RESULTS E-4031 (0.5 μmoI·L-1 )markedIy proIonged endocardiaI and epicardiaI APD90 and QT intervaI( P﹤0.01),and dramaticaIIy increased TDR(P﹤0.01). Spontaneous or programmed eIectricaI stimuIation-induced EAD and TdP were aIso observed in the modeI. VerapamiI(0.5,1.0 and 2.5 μmoI·L-1 )dose-dependentIy abbreviated endocardiaI and epicardiaI APD90 and QT intervaI(P﹤0.01),significantIy decreased TDR(P﹤0.01),and suppressed EAD and TdP in the LQT2 modeI. Concordant but stronger effects on the eIectro-physioIogicaI properties of the LQT2 modeI were noticed when nifedipine was perfused. CONCLUSlON VerapamiI inhibits TdP in the LQT2 modeI by reducing TDR and suppressing EAD.
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Objective To observe efifcacy and safety of catheter ablation for atrial ifbrillation (AF) occurring after surgical valve replacement in patients with rheumatic heart disease (RHD). Methods A total of 23 RHD patients with atrial ifbrillation after surgical valve replacement were enrolled in this study from 2008 to 2013. The clinical characteristics, ablation strategies and successful rate were investigated. Results All the cases included 8 males and 15 females (age, 51.0 ± 9.2 years). Valves replaced were isolated mitral valves (13/23, 56.5%) and multiple valves (10/23, 43.5%). Postoperative AF after cardiac surgery was paroxysmal in 14 patients (60.9%) and nonparoxysmal in 9 cases. Nine patients (39.1%) was in sinus rhythm before cardiac surgery, 4 in paroxysmal AF and 10 in non-paroxysmal AF. The mean interval between the catheter ablation AF and the surgical intervention was (6.9±5.8) years. The postoperative AF duration was (3.1±3.2) years, left and right atrial diameters were (44.1±5.9) mm and (48.1±9.0) mm respectively, left ventricular ejection fraction was 64.0%±8.3%, the mean ablation procedure duration was (156.8±46.6) min, and lfuoroscopy exposure averaged (27.3±11.2) min. Standard pulmonary vein isolation was performed in all cases by using ipsilateral circumferential ablation technique. Additional ablation, including complex fractionated atrial electrograms, mitral and tricuspid isthmus, and left atrial roof, was applied in most of the cases. After a mean follow-up of (29.7±21.2) months (median, 24 months), 60.9%of the patients remained free of AF, 1 died, and 2 lost to follow-up. Conclusions Catheter ablation for AF is effective and safe in patients with RHD after surgical valve replacement. Stepwise ablation strategy may be better for these patients.
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Objective To investigate the level and the source of inflammatory factors in patients with paroxysmal atrial fibrillation.Methods Thirty patients with paroxysmal atrial fibrillation were selected as observation group,and 20 cases of patients with paroxysmal supraventricular tachycardia were selected as control group.The blood samples of coronary sinus,right atria,left atria and femoral vein were consecutively collected during the procedure of radiofrequency ablation.The level of tumor necrosis factor (TNF)-α,soluble tumor necrosis factor receptor-1 (sTNFR1),and interleukin(IL)-6 was detected by ELISA separately and compared between two groups.Results The level of TNF-α and IL-6 of coronary sinus,right atria,left atria and femoral vein in observation group was significantly higher than that in control group [TNF-α:(4.45 ± 1.76) ng/L vs.(0.59 ± 0.36) ng/L,(6.67 ± 1.43) ng/L vs.(0.51 ± 0.30) ng/L,(8.35 ± 2.03) ng/L vs.(0.85 ± 0.50) ng/L,(9.97 ± 2.70) ng/L vs.(0.28 ± 0.29) ng/L,P=0.000;IL-6:(2.02 ± 0.87) ng/L vs.(1.04 ± 0.63) ng/L,(1.51 ± 0.68) ng/L vs.(0.74 ± 0.26) ng/L,(2.00 ± 0.51) ng/L vs.(0.88 ± 0.35) ng/L,(1.32 ±0.47) ng/L vs.(0.48 ±0.28) ng/L,P =0.000].The level of high sensitivity C reactive protein (hs-CRP) in observation group was significantly higher than that in control group [(2.41 ± 1.35) mg/L vs.(1.10 ±0.53) mg/L,P =0.002].The level of TNF-αof left atrium in observation group was significantly higher than that of other three sites (P=0.000).The level of IL-6 in the coronary sinus and femoral vein was significantly increased,compared with that in the right atria and left atria (P ＜ 0.05).The level of sTNFR 1 in the femoral vein,right atria and coronary sinus difference was not statistically significant (P ＞ 0.05),but was significantly higher than that in the left atria(P ＜ 0.05).The level of TNF-α,IL-6 and hs-CRP was correlated with the diameter of left atrium (LAD) (P ＜ 0.01 or ＜ 0.05).The level of sTNFR1 in left atria was positively correlated with LAD,and the level of sTNFR1 in right atria was negatively correlated with LAD (P ＜ 0.01).Conclusions The level of TNF-α,IL-6 and hs-CRP is increased in patients with paroxysmal atrial fibrillation.TNF-α and IL-6 may come from the heart and is related with the enlargement of left atrium.
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The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H(2)O(2), 100 μmol/L) was used to treat neurons for 24 h to induce oxidative stress. Exogenous SHH (3 μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pre-treat the neurons 30 min before H(2)O(2) treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H(2)O(2) treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the pro-apoptotic gene Bax by 12% and down-regulate the expression of the anti-apoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H(2)O(2)-induced apoptosis.
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The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H(2)O(2), 100 μmol/L) was used to treat neurons for 24 h to induce oxidative stress. Exogenous SHH (3 μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pre-treat the neurons 30 min before H(2)O(2) treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H(2)O(2) treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the pro-apoptotic gene Bax by 12% and down-regulate the expression of the anti-apoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H(2)O(2)-induced apoptosis.
Subject(s)
Animals , Rats , Cerebral Cortex , Metabolism , Hedgehog Proteins , Metabolism , Neurons , Metabolism , Neuroprotective Agents , Metabolism , Oxidative Stress , Physiology , Phosphatidylinositol 3-Kinase , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Rats, Sprague-DawleyABSTRACT
AIM: To investigate alteration of inward re ctifier potassium current (I K1) in atrial myocytes and mRNA expression of gene Kir2.1 encoding I K1 in atrial myocardial tissue in patients with chronic atrial fibrillation (AF) compared to that with sinus rhythm (SR).METHODS: Single myocytes were isolated by enzymatic dissociation with the chunk method an d the ionic current was recorded using whole cell patch clamp technique. The sem i-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of Kir2.1 in atrial myocardial tissue, and the g ene GAPDH was used as an internal control.RESULTS: (1) The I K1 density was increased in AF group at hyperpolarizing pot entials, at -120 mV the current densities was (-5.71?0.65) pA/pF in AF group (n=28 cells from 7 patients) and (-4.26?1.22) pA/pF in SR group (n=35 cells from 9 patients) (P0.05).CONCLUSIONS: The increase in I K1 at hyperpolarizing potentials may be related to th e atrial electrophysiological remodeling in chronic human AF. The increased I K1 density in atrial myocytes in AF group without alteration of Kir2.1 mRNA expression in atrial tissue suggests that I K1 may be mediated at post-transcriptional levels.