Radiofrequency catheter ablation of ventricular arrhythmias arising from the region above pulmonary valve.

BACKGROUND: Ventricular arrhythmias (VAs) arising from the origin above pulmonary valve lack comprehensive investigation. This study aimed to disclose the characteristics and radiofrequency catheter ablation (RFCA) outcomes for those VAs. METHODS: One hundred six VAs arising from the region above pulmonary valve treated with RFCA were included in this study. RESULTS: Seventy-five cases were identified in the pulmonary sinus cusps (PSCs, 32 in left sinus cusp (PLC), 15 in right (PRC), 28 in anterior (PAC)) and 31 cases were in the main stem of pulmonary artery (MSPA, 18 above PLC (LMSPA), 3 above PRC (RMSPA), 10 above PAC (AMSPA)). Compared with PSCs VAs, MSPA VAs exhibited a higher R wave amplitude in the inferior leads, a total inferior R amplitude > 5.1 mV predicting MSPA origins. LMSPA, RMSPA and AMSPA VAs resembled PLC, PRC and PAC VAs in electrocardiographic characteristics respectively. No electrophysiological differences were found between PSCs and MSPA VAs. The irrigated-up catheter and R0 Swartz long sheath were more utilized for ablation of PSCs VAs than for MSPA VAs. All these VAs were successfully eliminated by RFCA. CONCLUSION: VAs arising from the origin above pulmonary valve were common. Based on certain electrocardiographic characteristics, they could be roughly located, which contributed to an effective RFCA.

Sodium Houttuyfonate Alleviates Post-infarct Remodeling in Rats via AMP-Activated Protein Kinase Pathway.

With the chronic ischemia persisting after acute myocardial infarction, the accompanying low-degree inflammation and subsequent fibrosis result in progression of cardiac remodeling and heart failure. Recently, Sodium Houttuyfonate (SH), a pure compound extracted from Houttuynia cordata, has been confirmed exerting anti-inflammatory and anti-fibrotic effects under diseased situations. Here, we aimed to investigate whether SH could reverse the cardiac remodeling post-myocardial infarction by alleviating cardiac inflammation and fibrosis. Left anterior descending coronary artery of adult male Sprague-Dawley rats was ligated to elicit myocardial infarction. Low and high dose of SH was administered by oral gavage for four consecutive weeks post-myocardial infarction. Long-term SH treatment decreased heart rate, heart weight/ body weight (HW/BW), and left ventricle weight/body weight (LVW/BW), reduced cardiac expression of brain natriuretic peptide (BNP), improved left ventricular heart function, and ameliorated the histopathological changes caused by myocardial infarction. Western blotting revealed the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), collagen I, and collagen III of the infarcted ventricle were reduced by SH treatment. Meanwhile, we found that SH treatment post-myocardial infarction activated AMP-activated protein kinase (AMPK) and suppressed nuclear factor-κB p65 (NF-κB p65). Furthermore, on H9C2 cells induced hypoxic injury with cobalt chloride (CoCl2), the reduction of inflammatory cytokines (IL-6, TNF-α, and TGF-ß), activation of AMPK, and suppression of NF-κB p65 were also observed by SH treatment. However, transfection of H9C2 with AMPKα siRNA blunted the suppression of NF-κB p65 and inflammatory cytokines (IL-6, TNF-α, and TGF-ß) by SH post-hypoxia. Taken together, these findings suggested that long-term administration of SH post-myocardial infarction reduced cardiac inflammatory and fibrotic responses, and reversed cardiac remodeling process. The underlying mechanism may be activating AMPK and suppressing NF-κB pathway.

Case presentation: implantation of cardiac resynchronization therapy pacemaker via the coronary sinus in a patient with triple valve replacement.

BACKGROUND: In patients with triple valve replacement developing third-degree atrioventricular block (AVB), the most appropriate approach for permanent pacemaker implantation remains questionable. CASE PRESENTATION: In this case presentation, we first described the approach of implantation of the cardiac resynchronization therapy pacemaker (CRT-P) via one bipolar pacing lead in middle cardiac vein (MCV) and one quadripolar pacing lead in anterior interventricular vein (AIV) in a patient developing complete AVB, who had been previously diagnosed with rheumatic valvular heart disease with triple valve replaced. After the CRT-P implantation, the two pacing leads in coronary sinus (CS) provided a dual-site ventricular pacing from the anterior septum and posterior septum, which resulted in a narrow QRS complex and an increased ventricular synchrony. During the long-term follow-up, no deterioration of heart function was documented and pacing parameters remained good. CONCLUSION: In this patient developing complete AVB with triple valve replaced, our approach of CRT-P implantation provides an effective and reliable ventricular pacing, and is an alternative option when transvenous right ventricular pacing, transseptal left ventricular pacing and transpericardial epicardium pacing are not possible. Further prospective randomized trials are required to confirm the efficiency of our approach of dual-site ventricular pacing by CRT-P in this kind patients.

Visual deprivation induce cross-modal enhancement of olfactory perception.

The underlying mechanisms responsible for enhanced olfactory perception of congenital blind humans remain elusive so far. Here, animal behavioral test showed that congenital visual deprivation (from postnatal day 0-28) or one-week visual deprivation during juvenile stage (from postnatal day 21-28) could reduce the latency time of food-seeking but increase the odor discrimination performance of rodents. The enhanced olfactory perception induced by one-week visual deprivation could be returned to base level when visual input was recovered. Accordingly, local field potential (LFP) oscillation recording in vivo showed that the power of high-frequency ß and γ oscillations were increased in olfactory bulb (OB) and anterior piriform cortex (aPC) of vision deprived animals. This research discovered the enhancement of olfactory perception and adaptive plasticity of oscillations in olfactory system of rodents induced by visual deprivation, which may facilitate better understanding of mechanisms underlying cross-modal plasticity.

Martentoxin: a unique ligand of BK channels.

The large-conductance calcium-activated potassium (BK) channels distributed in both excitable and non-excitable cells are key participants in a variety of physiological functions. By employing numerous high-affinity natural toxins originated from scorpion venoms the pharmacological and structural characteristics of these channels tend to be approached. A 37-residue short-chain peptide, named as martentoxin, arising from the venom of the East-Asian scorpion (Buthus martensi Karsch) has been investigated with a comparatively higher preference for BK channels over other voltage-gated potassium (Kv) channels. Up to now, since the specific drug tool probing for clarifying structure-function of BK channel subtypes and related pathology remain scarce, it is of importance to illuminate the underlying mechanism of molecular interaction between martentoxin and BK channels. As for it, the current review will address the recent progress on the studies of pharmacological characterizations and molecular determinants of martentoxin targeting on BK channels.

Pharmacological kinetics of BmK AS, a sodium channel site 4-specific modulator on Nav1.3.

OBJECTIVE: In this study, the pharmacological kinetics of Buthus martensi Karsch (BmK) AS, a specific modulator of voltage-gated sodium channel site 4, was investigated on Na(v)1.3 expressed in Xenopus oocytes. METHODS: Two-electrode voltage clamp was used to record the whole-cell sodium current. RESULTS: The peak currents of Na(v)1.3 were depressed by BmK AS over a wide range of concentrations (10, 100, and 500 nmol/L). Most remarkably, BmK AS at 100 nmol/L hyperpolarized the voltage-dependence and increased the voltage-sensitivity of steady-state activation/inactivation. In addition, BmK AS was capable of hyperpolarizing not only the fast inactivation but also the slow inactivation, with a greater preference for the latter. Moreover, BmK AS accelerated the time constant and increased the ratio of recovery in Na(v)1.3 at all concentrations. CONCLUSION: This study provides direct evidence that BmK AS facilitates steady-state activation and inhibits slow inactivation by stabilizing both the closed and open states of the Na(v)1.3 channel, which might result from an integrative binding to two receptor sites on the voltage-gated sodium channels. These results may shed light on therapeutics against Na(v)1.3-targeted pathology.

Exploring the obscure profiles of pharmacological binding sites on voltage-gated sodium channels by BmK neurotoxins.

Diverse subtypes of voltage-gated sodium channels (VGSCs) have been found throughout tissues of the brain, muscles and the heart. Neurotoxins extracted from the venom of the Asian scorpion Buthus martensi Karsch (BmK) act as sodium channel-specific modulators and have therefore been widely used to study VGSCs. α-type neurotoxins, named BmK I, BmK αIV and BmK abT, bind to receptor site-3 on VGSCs and can strongly prolong the inactivation phase of VGSCs. In contrast, ß-type neurotoxins, named BmK AS, BmK AS-1, BmK IT and BmK IT2, occupy receptor site-4 on VGSCs and can suppress peak currents and hyperpolarize the activation kinetics of sodium channels. Accumulating evidence from binding assays of scorpion neurotoxins on VGSCs, however, indicate that pharmacological sensitivity of VGSC subtypes to different modulators is much more complex than that suggested by the simple α-type and ß-type neurotoxin distinction. Exploring the mechanisms of possible dynamic interactions between site 3-/4-specific modulators and region- and/or species-specific subtypes of VGSCs would therefore greatly expand our understanding of the physiological and pharmacological properties of diverse VGSCs. In this review, we discuss the pharmacological and structural diversity of VGSCs as revealed by studies exploring the binding properties and cross-competitive binding of site 3- or site 4-specific modulators in VGSC subtypes in synaptosomes from distinct tissues of diverse species.

Deglycosylation altered the gating properties of rNav1.3: glycosylation/deglycosylation homeostasis probably complicates the functional regulation of voltage-gated sodium channel.

OBJECTIVE: To examine the effect of deglycosylation on gating properties of rNav1.3. METHODS: rNav1.3 was expressed in Xenopus oocyte, with glycosylation inhibition by using tunicamycin. Two-electrode voltage clamp was employed to record the whole-cell sodium current and data were analyzed by Origin software. Those of glycosylated rNav1.3 were kept as control. RESULTS: Compared with glycosylated ones, the steady-state activation curve of deglycosylated rNav1.3 was positively shifted by about 10 mV, while inactivation curve was negatively shifted by about 8 mV. CONCLUSION: Glycosylation altered the gating properties of rNav1.3 and contributed to the functional diversity.

Comparative pharmacology and cloning of two novel arachnid sodium channels: Exploring the adaptive insensitivity of scorpion to its toxins.

Scorpion toxins have been found lacking effect on Na(+) current of its own sodium channel, whereas the molecular mechanism remains mystery. In this study, the binding affinity of pharmacologically distinct scorpion toxins was found much weaker to scorpion (Buthus martensii) nerve synaptosomes than to spider (Ornithoctonus huwena) ones. The sodium channel cDNA from these two species were further cloned. The deduced proteins contain 1871 and 1987 amino acids respectively. Several key amino acid substitutions, i.e., A1610V, I1611L and S1617K, are found in IVS3-S4 constituting receptor site-3, and for receptor site-4, two residues (Leu-Pro) are inserted near IIS4 of scorpion sodium channel.