Dongjie Xu

Rapid component IKr of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by α1-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways

Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

An algorithm to predict the site of origin of focal atrial tachycardia.

Background: Only a few algorithms for predicting the site of origin of focal atrial tachycardia (AT) have been reported. We aimed to develop a new and more effective algorithm.

Increased Response to β2-Adrenoreceptor Stimulation Augments Inhibition of IKr in Heart Failure Ventricular Myocytes

Background Increasing evidence indicates that the rapid component of delayed rectifier potassium current (IKr) is modulated by α- and β-adrenergic stimulation. However, the role and mechanism regulating IKr through β2-adrenoreceptor (β-AR) stimulation in heart failure (HF) are unclear. Methodology/Principal Findings In the present study, we investigated the effects of fenoterol, a highly selective β2-AR agonist, on IKr in left ventricular myocytes obtained from control and guinea pigs with HF induced by descending aortic banding. IKr was measured by using whole cell patch clamp technique. In control myocytes, superfusion of fenoterol (10 µM) caused a 17% decrease in IKr. In HF myocytes, the same concentration of fenoterol produced a significantly greater decrease (33%) in IKr. These effects were not modified by the incubation of myocytes with CGP-20712A, a β1-AR antagonist, but were abolished by pretreatment of myocytes with ICI-118551, a β2-AR antagonist. An inhibitory cAMP analog, Rp-cAMPS and PKA inhibitor significantly attenuated fenoterol-induced inhibition of IKr in HF myocytes. Moreover, fenoterol markedly prolonged action potential durations at 90% (APD90) repolarization in HF ventricular myocytes. Conclusions The results indicate that inhibition of IKr induced by β2-AR stimulation is increased in HF. The inhibitory effect is likely to be mediated through a cAMP/PKA pathway in HF ventricular myocytes.

Premature ventricular contractions originating from the right ventricular outflow tract: three-dimensional distribution of the target sites and their electrocardiographic characteristics.

1 The purpose of the present study was to explore the relationship between electrocardiogram (ECG) patterns of right ventricular outflow tract (RVOT) premature ventricular contractions and the three‐dimensional distribution of the target sites. 2 Thirty‐three consecutive patients were included in the study. The target sites were identified by non‐contact mapping and confirmed by successful ablation. The distribution of the target sites in the three‐dimensional reconstructed geometry of the RVOT was classified in three directions: (i) anterior (A)/posterior (P); (ii) free wall (F)/septal (Se); and (iii) superior (Su)/inferior (I). The ECG characteristics were then analysed according to the three‐dimensional distribution of the target sites. 3 The following indices were helpful to identify the position of the target site: (i) QRS duration (≥ 150 msec = F; < 150 msec = Se; P < 0.05); (ii) the R wave pattern in the inferior leads (RR′ or Rr′ = F; R = Se; P < 0.05); (iii) the R wave amplitude in the inferior leads (high = Se; low = F; P < 0.05); (iv) the initial r wave width in lead V1 (wide = F; narrow = Se; P < 0.05); (v) the QS wave amplitude in aVR and aVL (if aVR < aVL, A; if aVR ≥ aVL, P; P < 0.05); and (vi) the initial r wave amplitude in lead V1 and V2 (if V1 ≥ 0.15 mV and V2 ≥ 0.3 mV, Su; if V1 < 0.15 mV or V2 < 0.3 mV, I; P < 0.05). 4 In conclusoin, the ECG characteristics were associated with target site locations in all three directions.

NEGATIVE REGULATION OF QUINONE REDUCTASE 2 BY RESVERATROL IN CULTURED VASCULAR SMOOTH MUSCLE CELLS

1 Resveratrol, a polyphenol in red wine, has a cardioprotective effect. Resveratrol‐targeting protein (RTP) has been purified using a resveratrol affinity column (RAC) and has been identified as quinone reductase type 2 (NQO2). We hypothesize that NQO2 is the target protein of resveratrol in vascular smooth muscle cells (VSMC) and that resveratrol inhibits proliferation of VSMC through its action on NQO2. In the present study, we investigated the correlation between NQO2 regulation and cell proliferation in VSMC in response to resveratrol treatment. 2 The RTP was purified using RAC and was detected with a NQO2 polyclonal antibody. The VSMC were incubated with resveratrol (1, 10 and 50 µmol/L) for 24, 48 and 72 h. Cell proliferation was detected by cell counting and bromodeoxyuridine (BrdU) assay. A lentiviral vector incorporating NQO2 short interference (si) RNA of short hairpin design was constructed and transduced into VSMC. Real‐time quantitative polymerase chain reactionwas used to measure NQO2 mRNA levels; NQO2 expression was determined by western blot analysis. 3 Using RAC, we extracted a 26 kDa protein from aortic smooth muscle, which was referred to as RTP‐26. Proliferation of VSMC was inhibited by resveratrol in a concentration‐ and time‐dependent manner. The mRNA and protein expression of NQO2 was also repressed by resveratrol in a concentration‐ and time‐dependent manner. A similar pattern of inhibition was observed for cells treated with resveratrol (25 µmol/L) as for cells transduced with a lentiviral vector containing siRNA sequences against NQO2. 4 Collectively, these data indicate that the suppression of VSMC proliferation mediated by resveratrol correlates with NQO2 downregulation.

Tpeak-Tend interval as a new risk factor for arrhythmic event in patient with Brugada syndrome

Abstract Objective To evaluate Tpeak-Tend(Tp-e) interval in surface standard ECG as a new risk factor for arrhythmic event in patient with Brugada syndrome. Methods 23 male patients with Brugada syndrome and 20 male patients with paroxysmal supraventricular tachycardia(PSVT) as the control group were investigated in this study. Tp-e interval in surface standard ECG was compared between BrS and PSVT patients. Results Tp-e interval in BrS patients was significantly longer than that in PSVT patients (109.57 ± 2.86 ms vs. 88.50 ± 3.08ms, P P P P > 0.05). Conclusion The prolongation of Tp-e interval could serve as a new noninvasive event predictor for arrhyth- mic events in patients with Brugada syndrome.

Predictors of Post Coronary Artery Bypass Grafting Atrial Fibrillation

Objective: To investigate the incidence and relative risk factors of post coronary artery bypass grafting(post-CABG) atrial fibrillation (AF). Methods: 312 patients with CABG were reviewed and divided into an AF group and a non-AF group. Statistical analysis was used to compare the data between the two groups and screen for risk factors of post-CABG AF. Results: 103/312 (33.01%) patients developed post-CABG AF. Univariate analysis showed that patients in AF group compared with those in non-AF group were more likely to have advanced age (≥70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement (≥40 mm), a history of AF, prolonged p-wave duration (≥120 ms) and increased number of grafts (≥3). Multivariate logistic regression analysis showed that advanced age (≥70 years), early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement (≥40 mm) and a history of AF were highly related to post-CABG AF. Conclusion: The incidence of AF in patients following CABG was 33.01% in this study. Advanced age, early postoperative withdrawal of β-blockers, hypertension, left atrial enlargement and a history of AF were independent risk factors of post-CABG AF.

Termination of polymorphic ventricular tachycardia storm by catheter ablation in a patient with cardiomyopathy induced by incessant idiopathic left ventricular tachycardia.

We detail findings in a patient with incessant idiopathic left ventricular tachycardia (ILVT), induced cardiomyopathy, and an “electrical storm” consisting of recurrent polymorphic ventricular tachycardia (PVT). Catheter ablation not only eradicated the ILVT, but also additionally suppressed recurrent PVT. These findings suggest that the recurrent PVT storm in this patient related to long‐standing tachycardia‐induced cardiac electrical remodeling that led to QT prolongation.

Narrow QRS Tachycardia with Ventriculoatrial Dissociation Mediated by a Left Fasciculoventricular Fiber

A 30-year-old man presented with narrow QRS tachycardia. The intracardiac electrocardiogram showed an atrial-HIS (AH) interval of 75 msec and a HIS-ventricular (HV) interval of 44 msec during baseline. Atrial incremental pacing revealed HV shortening, with apparent incomplete right bundle branch block (RBBB) morphology without QRS complex axis deviation. The induced tachycardia exhibited several QRS morphologies: a narrow QRS, complete RBBB and complete left bundle branch block (LBBB) morphology. Spontaneous conversion of the QRS pattern from wide to narrow was observed. The cycle length of the tachycardia was significantly shortened (from 316 to 272 ms) from LBBB morphology to narrow QRS complex. The atrial activation was dissociated from the ventricular activation during all tachycardias. Each QRS complex during tachycardia was preceded by a HIS deflection and HV interval was 35 ms, which was shorter than that of sinus rhythm. HIS deflection was earlier than right bundle potential during all kinds of tachycardia. This tachycardia is most likely mediated by a left fasciculoventricular fiber which connects the HIS bundle below the atrioventricular node to the myocardial tissue of the left ventricle. The HIS-Purkinje system is used as an antegrade conduction limb and the fasciculoventricular fiber as a retrograde limb in the tachycardia circuit.