Predictive value of rs2200733 polymorphism for atrial fibrillation recurrence after radiofrequency catheter ablation / 医学研究生学报

Objective The recurrence rate of atrial fibrillation (AF) after radiofrequency catheter ablation (RFCA) remains relatively high. The aim of this study was to investigate the predictive value of rs2200733 polymorphism for AF recurrence after RFCA. Methods Fifty-three AF patients underwent RFCA guided by the magnetic navigation system between July 2015 and September 2016 in Wuxi People’s Hospital. We obtained the baseline data on the patients, conducted genotyping for rs2200733 variants, and followed up the patients for symptoms and complications by electrocardiography (ECG) and dynamic ECG. Using Cox survival analysis, we determined the independent predictors of AF recurrence after RFCA and the sensibility and specificity of predicting AF recurrence at 12 and 24 months post-operatively. Results All the patients were Han Chinese, followed-up for 21.6 ± 9.5 months, and 25 (47.2%) of them experienced AF recurrence at 6.6 ± 5.3 months after RFCA. Kaplan-Meier survival analysis revealed a significant association between rs2200733 polymorphism and AF recurrence in the additive and recessive models (P < 0.001), and multivariate Cox analysis showed the rs2200733 polymorphism (recessive model) to be an independent predictor of post-RFCA AF recurrence (OR = 3.184, 95% CI: 1.378-7.357, P = 0.007). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of rs2200733 TT in predicting AF recurrence at 12 months were 64%, 81%, 70%, 76% and 74%, and those at 24 months were 60%, 82%, 75%, 70%, and 72%, respectively. Conclusion The rs2200733 polymorphism is an independent predictor of AF recurrence after RFCA, and its high specificity indicates that it could be used as a tool for screening Han Chinese patients with AF for RFCA.

13,14-EpDPE dilates coronary arterioles in rats by activating BK channels / 医学研究生学报

Objective The mechanisms of docosahexaenoic acid (DHA) protecting the cardiovascular system have not yet been clarified. This study was to investigate the vasorelaxative effect of 13,14-epoxy docosapentaenoic acid (13,14-EpDPE) on coronary arterioles in normal rats and its action mechanisms.Methods We isolated coronary artery smooth muscle cells (CASMCs) from normal rats by enzyme digestion, examined the open probabilities of the large conductance calcium-activated potassium (BK) channels in inside-out single channel configuration in the presence of different concentrations (0, 1, 10 and 100 pmol/L) of 13,14-EpDPE, and recorded the BK currents with the patch clamp in whole cell configuration. Then we assessed the coronary arterial relaxation by measuring dilatory responses to 13,14-EpDPE in pre-contracted tissues with or without pre-treatment with iberiotoxin.Results In the presence of 0, 1, 10 and 100 pmol/L of 13,14-EpDPE, the open probabilities of the BK channels were 0.25±0.03, 0.34±0.03, 0.44±0.06 and 0.85±0.16 (n=6), respectively, significantly increased at 100 pmol/L as compared with 0, 1 and 10 pmol/L (P<0.05). The BK channels were activated by 13,14-EpDP in a concentration-dependent manner and its half-effect concentration was (15.94±1.21) pmol/L. The current density was increased from (58.27±16.35) to (95.94±23.00) pA/pF (P=0.002) after 10 pmol/L 13,14-EpDP perfusion when the stimulation voltage was 100 mV. 13,14-EpDPE dilated the isolated coronary arterioles in a dose-dependent manner, and its effects were abolished after pre-treatment with iberiotoxin (100 nM).Conclusion 13,14-EpDPE can dilate coronary arterioles by activating BK channels in CASMCs, which might be one of the mechanisms underlying its protective effect on the cardiovascular system.

Changes of open probability of large conductance Ca(2+)-activated K(+) channels in diabetic coronary smooth muscle cells of rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the changes of open probability (Po) of large conductance Ca(2+)-activated K(+) channel (BK channel) in diabetic coronary smooth muscle cells and elucidate the underlying cellular electrophysiology mechanisms of coronary dysfunction.</p><p><b>METHODS</b>Rat coronary smooth muscle cells were isolated from control group and diabetic group. BK single channel currents were recorded by patch clamp technique in inside-out configuration. Open probabilities were calculated and compared between two groups. After exposure to DHS-1, a specific BK channel activator, Po at 0.2 and 1 µmol/L free Ca(2+) were compared between control and diabetic groups.</p><p><b>RESULTS</b>In the presence of 0.2 µmol/L free Ca(2+), the Po at baseline was significantly lower in diabetic rats than in control rats (0.0032 ± 0.0012 vs. 0.095 ± 0.036, P < 0.05). Cytoplasmic application of DSH-1 significantly increased the Po to 0.335 ± 0.096 (P < 0.05 vs. baseline) in control rats, whereas DSH-1 had no effect in diabetic rats (Po = 0.022 ± 0.018, P > 0.05 vs. baseline). In the presence of 1 µmol/L free Ca(2+), the Po at baseline was also significantly lower in diabetic rats than in control rats (0.210 ± 0.055 vs. 0.458 ± 0.077, P < 0.05). Cytoplasmic application of DHS-1 further robustly enhanced Po to 0.823 ± 0.019 (P < 0.05 vs. baseline) in control rats and to 0.446 ± 0.098 in diabetic rats (P < 0.05 vs. baseline of diabetic rats; P < 0.05 vs. control rats with DHS-1).</p><p><b>CONCLUSION</b>The decrease of Po of BK single channel in coronary smooth muscle cells may be a potential cause for coronary dysfunction in diabetic rats.</p>

Molecular mechanisms of diabetic coronary dysfunction due to large conductance Ca2⁺-activated K⁺ channel impairment / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca(2+)-activated K(+) (BK) channel activities in coronary dysfunction in streptozotocin-induced diabetic rats.</p><p><b>METHODS</b>Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats.</p><p><b>RESULTS</b>BK currents (defined as the iberiotoxin-sensitive K(+) component) contribute (65 ± 4)% of the total K(+) currents in freshly isolated coronary smooth muscle cells and > 50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca(2+) is impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 (a specific BK channel b(1) subunit activator) robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca(2+) and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 mmol/L Ca(2+). Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-b(1) protein expression in diabetic vessels, without altering the BK channel α-subunit expression. Although the cytosolic Ca(2+) concentration of coronary arterial smooth muscle cells was increased from (103 ± 23) nmol/L (n = 5) of control rats to (193 ± 22) nmol/L (n = 6, P < 0.05) of STZ-induced diabetic rats, reduced BK-b(1) expression made these channels less sensitive to intracellular Ca(2+), which in turn led to enhanced smooth muscle contraction.</p><p><b>CONCLUSIONS</b>Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-b(1) expression and reduction of the b(1)-mediated BK channel activation in diabetic vessels.</p>

Evaluation of left ventricular function and twist in patients with diabetic cardiovascular autonomic neuropathy by speckle tracking imaging / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate left ventricular (LV) function and twist in patients with diabetic cardiovascular autonomic neuropathy (CAN) by two-dimensional speckle tracking imaging (STI).</p><p><b>METHODS</b>STI was performed in 56 subjects with type 2 diabetes mellitus (DM) (35 with DM only: group A, 21 with CAN: group B) and 34 normal subjects (Control) from LV short-axis view. LV peak systolic, peak early (E') and peak late (A') diastolic circumferential strain in 18 myocardial segments were measured at the levels of mitral annulus, papillary muscle and apex and the rotation at mitral annulus and apex levels were also measured. LV peak systolic and the ratio of E' and A' of global and three levels, twist, untwisting rate and untwisting half-time were calculated.</p><p><b>RESULTS</b>In group A, compared with control group, LV peak systolic radial circumferential strain has no significant difference (P > 0.05), E'/A' was reduced (P < 0.05), twist at aortic valve closure and twist at mitral valve opening were significantly increased (P < 0.05), untwisting rate reduced, and untwisting half time delayed. In group B, compared with control group and group A, circumferential strain parameters [(-12.64 ± 6.49)% vs. (-19.11 ± 9.98)% and (-21.14 ± 10.13)%, P < 0.05] and E'/A' [(0.90 ± 0.35) vs. (1.24 ± 0.47) and (1.98 ± 0.63), P < 0.05] were significantly decreased, twist at aortic valve closure [(19.08 ± 5.62)° vs. (16.57 ± 2.84)° and (14.36 ± 4.06)°, P < 0.05] and twist at mitral valve opening [(13.99 ± 2.31)° vs. (11.36 ± 2.63)° and (9.04 ± 5.63)°, P < 0.05] were significantly increased, untwisting rate [(0.40 ± 0.28)%/ms vs. (0.46 ± 0.14)%/ms and (0.53 ± 0.21)%/ms, P < 0.05] reduced, and untwisting half time [(489.61 ± 97.14) ms vs. (445.21 ± 54.53) ms and (410.60 ± 50.23) ms, P < 0.05] delayed.</p><p><b>CONCLUSION</b>Speckle tracking imaging could be used to evaluate early changes on LV twist deformation and LV systolic function in patients with type 2 diabetes mellitus.</p>

Mechanism related to docosahexaenoic acid induced large conductance calcium-activated potassium channel currents increase in coronary smooth muscle cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of enhanced large conductance calcium-activated potassium channel currents (BK) in coronary smooth muscle cells (SMCs) by docosahexaenoic acid (DHA).</p><p><b>METHODS</b>Coronary SMCs were isolated by enzyme digestion. Potassium channels in coronary SMCs were identified by applications of different potassium blockers. Effects of DHA and its metabolite 16, 17-epoxydocosapentaenoic acid (16, 17-EDP) on BK channels in the absence and presence of cytochrome P450 epoxygenase inhibitor SKF525A were studied by patch clamp in whole-cell configuration.</p><p><b>RESULTS</b>BK channels were widely distributed in SMCs, and BK currents in normal SMCs accounted for (64.2 ± 2.7)% of total potassium currents (n = 20). DHA could activate BK channels, and its 50% effective concentration (EC(50)) was (0.23 ± 0.03) µmol/L, however, the effect of DHA on BK channels was abolished after SMCs were incubated with cytochrome P450 epoxygenase inhibitor SKF525A. 16, 17-EDP, a metabolite of DHA, could reproduce the effects of DHA on BK channels, and its EC(50) was (19.7 ± 2.8) nmol/L.</p><p><b>CONCLUSION</b>DHA and metabolites can activate BK channels and dilate coronary arteries through activating cytochrome P450 epoxygenase pathway.</p>

Changes of large conductance Ca(2+)-activated K(+) channels on coronary smooth muscle cells from diabetic rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the changes of large conductance Ca(2+)-activated K(+) channel (BK channel) on coronary smooth muscle cells from diabetic rats.</p><p><b>METHODS</b>Streptozotocin-induced rat diabetic animal model was used. Coronary smooth muscle cells were isolated by enzyme digestion. BK currents in control and diabetic groups were recorded by patch clamp technique in whole cell configuration, and BK channel protein expression was detected by Western blot. Calcium concentration was measured by fluorescence assay.</p><p><b>RESULTS</b>Compared with control group, BK current densities in diabetic group were significantly decreased when test potentials > 100 mV (P < 0.05). BK current densities were (275 ± 40) pA/pF in control group (n = 8) and (70 ± 10) pA/pF in diabetic group (n = 6) at 150 mV test potentials. α-subunit protein expression was similar between the groups (P > 0.05), however, β1-subunit protein expression was significantly reduced in diabetic group than in control group (P < 0.05). Calcium concentrations were significantly increased in diabetic group control group (151 ± 18) nmol/L (n = 6) than in control group (92 ± 7) nmol/L (n = 5, P < 0.05).</p><p><b>CONCLUSION</b>Observed β1-subunit downregulation, BK current density decrease and cytosolic calcium concentration increase in smooth muscle cells of diabetic coronary arteries may be associated with coronary dysfunction in diabetic rats.</p>

Clinical characteristics of severe chronic heart failure patients with normal blood B-type natriuretic peptide / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the clinical features of severe chronic heart failure patients with normal B-type natriuretic peptide (BNP).</p><p><b>METHODS</b>A total of 57 patients with severe chronic heart failure (New York Heart Association class III and IV) were included in this prospective control study from Dec. 2002 to Oct. 2009. Group A included 13 patients with normal BNP (< 100 ng/L) and group B included 44 patients with increased BNP (> 100 ng/L). Group A patients were followup for (19.6 ± 14.7) months and group B patients for (72.5 ± 17.1) months.</p><p><b>RESULTS</b>The baseline clinical characteristics of two groups were comparable. Left ventricular end diastolic diameter (LVEDd) of group A was larger than group B [(70.56 ± 4.33) mm vs.(63.73 ± 3.75) mm, P < 0.05], the left ventricular ejection fraction (LVEF) of group A was lower than group B [(24.16 ± 2.50)% vs. (28.49 ± 2.63)%, P < 0.05]. The number of patents tolerating metoprolol in group A is lower than in group B (7/13 vs. 39/44, P < 0.05), and the tolerant dose of metoprolol in group A is lower than in group B [(12.5 ± 6.25) mg/d vs. (24.20 ± 11.22) mg/d, P < 0.05]. The level of BNP in group B were significantly higher at acute stages than at remission stages [(962.73 ± 165.00) ng/L vs. (876.24 ± 167.70) ng/L, P < 0.05], but remained unchanged in group A [(74.03 ± 11.18) ng/L vs. (71.38 ± 11.68) ng/L, P > 0.05]. The mortality of group A was higher than group B (11/12 vs. 6/44, P < 0.05). The binary logistic regression analysis (backward) showed that normal B-type natriuretic peptide was an independent predictor of cardiovascular mortality in patients with severe chronic heart failure (OR = 45.488, 95%CI = 5.322 - 388.791).</p><p><b>CONCLUSION</b>Normal BNP in patients with severe chronic heart failure suggests the exhaustion of BNP secretion and associated poor prognosis.</p>

Time distribution of ventricular arrhythmias in patients with Brugada syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To study the characterization of time distribution of ventricular arrhythmias in patients with Brugada syndrome (BrS) using Holter monitoring and ICD follow-up.</p><p><b>METHODS</b>Patients with BrS [all male, mean age (41.07 +/- 11.49) years], were divided into ventricular fibrillation (VF) group (n = 7) and no ventricular fibrillation (N-VF) group (n = 7). Premature ventricular capture (PVC) and VF episodes were detected by Holter monitoring and ICD recording.</p><p><b>RESULTS</b>The 24 hours total number of PVCs ranged from 0 to 74 (mean 9.61 +/- 17.23) in most of the patients and were similar between VF group and N-VF group. The percentage of PVC episodes in VF group was significantly higher than that in N-VF group from nocturnal time to early morning (22:00 to 7:00, 98.67% vs. 44.14%, P < 0.01). There were total 75 VF episodes during (23.18 +/- 17.96) months' follow-up in 5 patients with BrS, 93.3% of which occurred from nocturnal time to early morning (22:00 to 7:00).</p><p><b>CONCLUSIONS</b>The episodes of PVC were enriched from nocturnal time to early morning in BrS patients, this time distribution could be a new noninvasive risk stratification factor for BrS. The episodes of VF in BrS patients were also enriched from nocturnal time to early morning and this time characteristic of episodes of VF could be used to guide drug therapy.</p>

The electrophysiological study and implantable cardioverter defibrillator therapy for the patients with Brugada syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>Clinical observation of electrophysiological study and implantable cardioverter defibrillator (ICD) therapy in patients with Brugada syndrome.</p><p><b>METHODS</b>Ten patients (all male) with Brugada wave (spontaneous or propafenone test positive in ECG) underwent electrophysiological study (EPS). The mean age was (41 +/- 10) years. They had no structural heart disease with echocardiogram and the angiogram work-up. The ICD implanted in the patients with EPS-induced ventricular fibrillation in those who were available.</p><p><b>RESULTS</b>Three patients had the history of familial sudden cardiac death (SCD). Four patients had repeated syncope episodes, two of them had documented ventricular fibrillation during syncope episodes. The AH and HV intervals were 50 - 124 (86 +/- 21) ms and 41 - 84 (58 +/- 15) ms. The ventricular fibrillation was induced in four patients with syncope and atrioventricular reentry tachycardia in one patient with palpitation. Three patients had spontaneous or inducible atrial fibrillation. The ICD implanted in three patients with inducible ventricular fibrillation. Due to economic issue, one patient without ICD implantation had got SCD during follow-up. The patient with atrioventricular reentry tachycardia underwent a successful left atrioventricular accessory pathway ablation.</p><p><b>CONCLUSION</b>The Brugada patients with syncope and high rate of inducible ventricular fibrillation in EPS are the high risk population for SCD, in whom ICD should implant promptly to prevent SCD.</p>