Symmetrical recovery time course between impedance and intramyocardial temperature after bipolar radiofrequency ablation; Role of impedance monitoring to estimate temperature rise.

INTRODUCTION: During radiofrequency (RF) ablation, impedance monitoring has been used to avoid steam-pop caused by excessive intramyocardial temperature (IMT) rise. However, it is uncertain why the impedance decline is related to steam-pop and whether the impedance decline is correlated to IMT. METHODS: Twenty-one bipolar ablations (40 W, 30-g contact, 120 s) were attempted for seven perfused porcine myocardium. Immediately after ablation, a temperature electrode was inserted into the mid-myocardial portion, and the recovery process of impedance and its correlation to IMT were assessed. RESULTS: Transmural lesion was created in all 21 applications but steam-pop occurred in 5/21 applications with large impedance decline. In the 16 applications without steam-pop, impedance and IMT soon after ablation were 97.2 ± 4.0 Ω and 66.1 ± 4.8 °C, respectively. Reasonably high linear correlation was demonstrated between the maximum IMT after ablation and impedance differences before and after ablation. Recovery processes of the decreased impedance and the elevated IMT fit well to each equation of the single exponential decay function and showed symmetric shapes with no statistical difference of time constant (100.1 ± 34.5 s in impedance vs. 108.7 ± 27.3 s in IMT) and half-time of recovery (144.5 ± 49.8 s in impedance vs. 156.9 ± 39.4 s in IMT). Recovered impedance after ablation (104.8 ± 3.9 Ω) was 5.1 ± 2.0 Ω smaller than that before ablation (109.9 ± 2.7 Ω), suggesting several factors other than IMT rise participate in impedance decline in RF ablation. CONCLUSIONS: Recovery of impedance and IMT after ablation well correlated, which supports the usefulness of impedance monitoring for safe RF ablation.

Decreased heat sensitivity of lungfish TRPV1 revealed by the heterologous expression system.

In this study, we focused on TRPV1 of African lungfish, Protopterus annectens. During drought at high temperature, African lungfish can survive by undergoing into aestivation in mud cocoons. Therefore, lungfish is considered to have some specialized heat-sensor, TRPV1, for heat tolerance. Further, lungfish which shares similarities with fishes and amphibians, is one of important species for investigating the fish-tetrapod transition. Since fish TRPV1 and tetrapod TRPV1 have some differences, character of lungfish TRPV1 attracts attention. Here, we first cloned TRPV1 paralogue from lungfish, Protopterus annectens (lfTRPV1) and determined the chemical and thermal sensitivities of lfTRPV1 by two-electrode voltage clamp method using frog oocytes. We detected activation of lfTRPV1 by acid and 2-APB, but capsaicin-induced activation was not observed. The sensitivity to acid of lfTRPV1 was similar to that of rat TRPV1 (rTRPV1), but the 2-APB sensitivity of lfTRPV1 was relatively weaker than rTRPV1. Heat stimulation up to 44 °C did not activate lfTRPV1 and the heat-activation was not detected even on acid condition of pH6. This dramatically decreased heat-sensitivity of TRPV1 may contribute the heat tolerance of African lungfish. Moreover, this might be the property of ancient tetrapod-type TRPV1 gene.

Distribution of excitation recoverable myocardium after radiofrequency ablation and its relation to energy application time and irrigation.

INTRODUCTION: Radiofrequency (RF) catheter ablation induces excitation recoverable myocardium around durable core lesions, and its distribution may be different depending on energy delivery methods. METHODS AND RESULTS: In coronary perfusing porcine hearts, pacing threshold through the ventricle was measured using eight-pole (1-mm distance) needle electrodes vertically inserted into myocardium before, within 3 min after and 40 min after 40 W ablation with 10-g catheter contact (Group 1: irrigation catheter for 15 s, Group 2: irrigation catheter for 40 s, Group 3: nonirrigation catheter for 15 s, Group 4: nonirrigation catheter for 40 s). Ablation was accomplished in all 12 ablations in Groups 1-3 whereas in 8/12 ablations in Group 4 because of high-temperature rise. Within 3 min after ablation, 10.0 V pacing uncaptured electrodes were distributed from the surface to inside the myocardium, and its depth was deeper in 40 s than in 15 s ablation. 40 min after ablation, excitation recovery at one or more electrodes below the durable lesion was observed in all Groups. Excitation recovery electrodes were also observed on the surface in Group 1 but not the other Groups. Accordingly, the number of excitation-recovered electrodes were larger in Group 1 than the other Groups. CONCLUSIONS: Regardless of the ablation methods, excitation recoverable myocardium was present around 1.0 mm below the durable lesions. Lesions created by short application time using an irrigation catheter may have included large excitation recoverable myocardium soon after ablation because of the presence of reversible myocardium on well-irrigated myocardial surfaces.

Impedance-decline-guide power control long application time bipolar radiofrequency catheter ablation.

INTRODUCTION: Bipolar (BIP) radiofrequency (RF) ablation creates deep myocardial lesions but ideal energy application modes to treat ventricular arrhythmias originating from deep inside the thick myocardium have not been well established. An experimental study was performed to clarify whether high power and long application time BIP ablation were performable by impedance-decline-guide power control (PC) and whether it could create transmural lesions in the thick ventricle with a minimum risk of steam-pop. METHODS AND RESULTS: Perfused porcine ventricle (18.4 ± 2.3 mm) was placed in an experimental bath and BIP ablation (50 W) for 120 s was attempted with catheter contact of 30-g using two protocols; fixed power (FP) and impedance-decline-guide PC. In the latter protocol, BIP ablation was started from 50 W, while the energy was decreased to 40-20 W according to the impedance decline during RF ablation. FP ablation was attempted in 30 applications and the transmural lesion was created in all 30, although steam-pop occurred in 16/30 applications (53%). Low minimum impedance, large total impedance decline (TID), and %-TID were associated with the steam-pop occurrence. PC ablation was attempted in another 21 applications, and the transmural lesion was created in all 21 without steam-pop. PC ablation was superior to FP ablation (21/21 vs. 14/30, p < .001) in the creation of a transmural lesion without resulting in steam-pop. CONCLUSIONS: High power and long application time BIP ablation seems to be feasible according to the impedance-decline-guide approach, which could create transmural lesions in thick porcine ventricles with minimal risk of steam-pop.

Cloning and functional characterization of medaka TRPV4.

Medaka, Oryzias latipes is distributed in fresh water of South Asia. To study roles of TRPV4 in osmosensing and adaption mechanism of medaka during changes in salinity environment, we isolated the cDNA for TRPV4 from medaka (olTRPV4) and characterized it. The electrophysiological analysis using Xenopus oocytes revealed that olTRPV4 can be activated by a TRPV4-specific agonist, GSK1016790A and acid at pH 5. Further, olTRPV4 was sensitive to 2-APB. Although warm temperatures activate mammalian TRPV4, olTRPV4 was activated by cold and hot stimulation. The threshold for cold activation was determined as 13.13 ± 0.60 °C, and the heat-activation threshold was 40.26 ± 0.25 °C. Further, when olTRPV4-expressing oocytes were stimulated by hypotonic solution, an apparent activation was observed. We further found that the expression of this hypotonic sensor, olTRPV4 was significantly down-regulated in gills but up-regulated in brains of sea water-acclimated medaka. Results demonstrated that olTRPV4 must function as an osmosensor and play important roles in adaption mechanism of medaka fish in various salinity environments.

Unique high sensitivity to heat of axolotl TRPV1 revealed by the heterologous expression system.

The thermosensation mechanism plays critical roles in various animals living in different thermal environment. We focused on an axolotl, which is a tailed amphibian originally from Lake Xochimilco area in the Vally of Mexico, and examined its behavior response to heat stimulation. Mild heat at 33 °C induced noxious locomotive activity to axolotls, but the noxious response of another tailed amphibian, Iberian ribbed newt, was not observed at 33 °C. To explore the mechanism for the temperature sensitivity of axolotls, we isolated a cDNA of TRPV1. Using the degenerate primer PCR method, we identified the DNA fragment encoding axolotl TRPV1 (axTRPV1), and then cloned a full-length cDNA. We studied the chemical and thermal sensitivities of axTRPV1 by two-electrode voltage clamp method using Xenopus oocyte expression system. Capsaicin, acid, and 2-aminoethoxydiphenylborane apparently activated axTRPV1 channels in a dose-dependent manner. The analysis of thermal sensitivity showed that axTRPV1 was significantly activated by heat but not by cold. The average temperature threshold for heat-activation was 30.95 ±â€¯0.12 °C. This thermal activation threshold of axTRPV1 is unique and significantly low, when compared with the known thresholds of TRPV1s from various animals. Further, this threshold of axTRPV1 is well consistent with the observation of heat-induced behavior of axolotls at 33 °C, demonstrating that axolotl shows noxious response to mild heat mediated through axTRPV1.

Impedance decrement indexes for avoiding steam-pop during bipolar radiofrequency ablation: An experimental study using a dual-bath preparation.

INTRODUCTION: This experimental study was conducted to explore impedance monitoring for safely performing bipolar (BIP) radiofrequency (RF) ablation targeted to arrhythmia focus. METHODS AND RESULTS: Using a newly designed dual-bath experimental model, contact-force-controlled (20-g) BIP ablation (50 W, 60 s) was attempted for porcine left ventricle (17.0 ± 2.7 mm thickness). BIP ablation was successfully accomplished for 60 s in 75 of the 89 RF applications (84.3%), whereas audible steam-pop occurred in the other 14 RF applications (15.7%). Receiver operating characteristic analysis demonstrated the optimal predictive values regarding the occurrence of steam-pop as follows; thinner myocardial wall (≤14.8 mm), low minimum impedance (≤89 ohm), greater total impedance decrement (TID) (≤ -25 ohm) and %TID (≤ -22.5%). Greater impedance decrement was not observed immediately preceding the occurrence of steam-pop but appeared around 15 s before. Four steam-pops happened before reaching the optimal predictive values of minimum impedance, whereas all 14 steam-pops developed 11.5 ± 9.2 and 8.1 ± 8.1 s after reaching the optimal predictive values of TID and %TID, respectively. Total lesion depth (endocardial plus epicardial) was 10.7 ± 1.2 mm on average, and was well correlated with TID and %TID. Transmural lesion through the myocardial wall was created in 22 RF applications. CONCLUSION: Relatively thinner areas of the myocardium are likely to be at greater risk for steam-pop during BIP RF ablation. Lowering the RF application energy to reduce the impedance decrement may help to lessen this risk.

Patient-by-patient basis anti-tachycardia pacing for fast ventricular tachycardia with structural heart diseases.

BACKGROUND: Anti-tachycardia pacing (ATP) delivered from an implantable device is an important tool to terminate ventricular tachycardia (VT). But its real-world efficacy for fast VT has not been fully studied. METHODS: Using the database of Nippon-storm study, effect of patient-by-patient basis ATP programming for fast VT (≥188 bpm) was assessed for the patients with structural heart diseases. Fast VTs were divided into three groups depending on heart rate (HR); Group A was 188-209 bpm, and Group-B and Group-C were 210-239 bpm and ≥240 bpm, respectively. RESULTS: During a median follow-up of 28 months, 202 fast VT episodes (209 ± 19 bpm) were demonstrated in the 85 patients. ATP terminated 151 of the 202 episodes (74.8%) in total. The success rate of the ATP was not different among the three groups: 73.3% in Group A, 80.6% in Group B, and 66.7% in Group C. ATP success rate of >50% and >70% was 77.6% and 64.7% of the patients, respectively. Left ventricular ejection fraction (LVEF) was significantly higher in the patients with rather than without successful ATP therapy, and receiver operating characteristic (ROC) analysis revealed that LVEF of 23% was the optimal cut-off value. ATP was less effective in patients taking amiodarone, but etiology of the structural heart diseases, indication of the device implantation, and all Electrocardiogram (ECG) parameters were not useful predictors for successful ATP therapy. CONCLUSIONS: ATP highly terminated fast VT with wide HR ranges in patients with structural heart diseases, and should be considered as the first-line therapy for fast VT except for patients with very low LVEF.

Bepridil Inhibits Premature Ventricular Complexes Induced by Cardio-Sympathetic Nerve Stimulation in a Canine Experimental Model.

Sympathetic nerve activity has arrhythmogenic potential for ventricular arrhythmias associated with structural heart diseases. However, a sufficient amount of beta-blockers occasionally cannot be prescribed in some patients.An experimental study was performed to clarify the therapeutic effects of bepridil, a multiple ionic current inhibitor that does not affect beta-adrenergic receptors, for premature beats occurring during enhanced sympathetic nerve activity. Cardio-sympathetic nerve activity was augmented via stellate-ganglion (SG) stimulation in a canine model (n = 8), and the arrhythmogenic potential and anti-arrhythmic effects of bepridil (2 and 4 mg/kg intravenously) were assessed. For safe use, vagal-stimulation-induced slow HR and programmed electrical stimulation were applied to evaluate possible pro-arrhythmic effects of the drug. Heart rate variability (HRV) indexes were used to estimate cardio-autonomic nerve activity.Either side of the SG-stimulation increased BP and HR. Premature beats were induced in 10/16 SG-stimulations and it was more frequent in left (8/8) rather than right stimulation (2/8). Following 2 mg/kg drug administration, premature beats were still inducible in 8/16 stimulations (7/8 in left and 1/8 in right), but burden of the premature beats decreased from 87.1 ± 46.8 to 62.1 ± 42.6 beats. After 4 mg/kg administration, premature beats were inducible in one SG-stimulation. Proarrhythmic effects were not observed in all experiments. Steady-state HRV indexes and percent increases in SG-stimulation-induced BP-elevation and HR-acceleration were similar among the 3 periods (before, 2 and 4 mg/kg of the drug).Bepridil may be an option for ventricular arrhythmias developed during enhanced cardio-sympathetic nerve activity with minimal effect on autonomic nerve responses.

Therapy-Resistant Ventricular Arrhythmias Developed More Often in Advanced Than in Therapeutic Mild Hypothermic Condition.

Therapy-resistant ventricular arrhythmias can occur during accidental advanced hypothermic conditions. On the other hand, hypothermic therapy using mild cooling has been successfully accomplished with infrequent ventricular arrhythmia events.To further clarify the therapeutic-resistant arrhythmogenic substrate which develops in hypothermic conditions, an experimental study was performed using a perfusion wedge preparation model of porcine ventricle, and electrophysiological characteristics, inducibility of ventricular arrhythmias, and effects of therapeutic interventions were assessed at 3 target temperatures (37, 32 and 28°C).As the myocardial temperature decreased, myocardial contractions and the number of spontaneous beats deceased. Depolarization (QRS width, stimulus-QRS interval) and repolarization (QT interval, ERP) parameters progressively increased, and dispersion of the ventricular repolarization increased. At 28°C, VF tended to be inducible more frequently (1/11 at 37°C, 1/11 at 32°C, and 5/11 hearts at 28°C), and some VFs at 28°C required greater defibrillation energy to resume basic rhythm.An advanced but not a mild hypothermic condition had an enhanced arrhythmogenic potential in our model. In the advanced hypothermic condition, VF with relatively prolonged F-F intervals and a greater defibrillation energy were occasionally inducible based on the arrhythmogenic substrate characterized as slowed conduction and prolonged repolarization of the ventricle.

Genetic Diversity among Clouded Salamanders (Hynobius nebulosus) in Shiga Prefecture.

The Japanese clouded salamander (Hynobius nebulosus) is a lentic-breeding species distributed throughout western Japan. Threats, such as habitat loss, have led to it being categorized as a vulnerable species. To explore the phylogeographic features and population differentiation among clouded salamanders in Shiga prefecture, we analyzed sequences of the mitochondrial cytochrome b gene. DNA samples were collected from 29 distinct breeding sites, and 53 cytochrome b haplotypes were identified. On the basis of comparison of the composition and frequency of haplotypes in each breeding site, salamanders in each habitat appeared to have distinct characteristics. Significant genetic differentiation was observed in 93.3% of possible pairs of habitats in Shiga prefecture, and 67.7% of habitat pairs within the same locality were found to be significantly different. These results suggest that the salamanders' poor locomotion combined with topographic effects may have contributed to the diversity of locally distributed salamanders in Shiga. Phylogenetic analysis showed that haplotypes of H. nebulosus in Shiga can be divided into five groups (the Nagahama-Maibara group, Otsu group, Konan group 1, Konan group 2, and Takashima group), each with a distinct geographical distribution. Haplotypes of the Otsu group, however, were exceptionally widely distributed. The results of the present study will contribute to the future of H. nebulosus conservation management in Shiga.

Chemical and thermal sensitivity of medaka TRPA1 analyzed in heterologous expression system.

TRPA1 of insects and several tetrapod vertebrates except for those of rodents have been reported to be activated by noxious chemicals and also by high temperature with a relatively clear threshold. We previously analyzed the characteristics of two TRPA1 paralogs of zebrafish (zTRPA1a, b) and demonstrated that zTRPA1a is specialized for chemical sensing while zTRPA1b responds to thermal stimulations, that zTRPA1b responds to both cold and heat stimuli, and that heat stimulation gradually activates zTRPA1b without a clear threshold. In the medaka genome, a single TRPA1 (olTRPA1) gene is present. To examine if functional properties of olTRPA1 are similar to TRPA1 of land animals or either of zTRPA1a or zTRPA1b, we isolated a TRPA1 cDNA from medaka and performed functional analyses. OlTRPA1 showed a sensitivity to four noxious chemicals (allyl isothiocyanate, caffeine, carvacrol, methyl anthranilate). We observed that cold stimulation does not activate olTRPA1, but heat stimulation gradually activates olTRPA1 with an unclear threshold. Results suggested that a single TRPA1 functions as a chemical and thermal sensor in medaka, and that a gradual heat-activation without clear threshold might be a common feature for TRPA1 of fish living in water.

Electrode Contact Force-Controlled Bipolar Radiofrequency Ablation: Different Effects on Lesion Size between Dual- and Single-Bath Preparations.

BACKGROUND: During bipolar (BIP) radiofrequency (RF) ablation using two catheters in humans, each catheter is placed in separate cardiac chambers or spaces. We developed a contact force-controlled experimental preparation, and compared measurements made with two catheters placed in a single bath (SB), versus each catheter placed in separate baths, in order to assess the preparation-dependent differences in the results of BIP-RF ablation. METHODS: In the SB experiments, a porcine heart was placed in the center of the bath, while in the dual-bath (DB) experiments, it was placed between two half baths communicating through windows. RESULTS: The initial impedance was greatest (110.5 ± 7.2 Ω) with the BIP-DB, followed by the BIP-SB (92.0 ± 5.6 Ω) and the unipolar (UNIP) DB (84.9 ± 4.7 Ω) configurations. During 50-W ablation for 60 seconds at a 20-g contact force, the root mean square voltage was 75.7 ± 2.5 V in the BIP-DB, 68.0 ± 2.1 V in the BIP-SB, and 66.8 ± 2.0 V in the UNIP-DB. The mean surface lesion diameters were similar among the three configurations. However, the endocardial lesion depth was 5.60 ± 0.56 mm with the BIP-DB, 4.71 ± 0.64 mm with the BIP-SB, and 4.24 ± 0.58 mm with the UNIP-DB configuration. On average, the endocardial lesions were significantly deeper than the epicardial ones. CONCLUSIONS: BIP ablation created much deeper lesions as compared to UNIP ablation. Lesion depth could be different depending on experimental preparation, and contact force-controlled DB preparation may be a much more appropriate model for studying the effects of BIP ablation.

Sensitivities of Two Zebrafish TRPA1 Paralogs to Chemical and Thermal Stimuli Analyzed in Heterologous Expression Systems.

Transient receptor potential A1 (TRPA1) is the only member of the mouse, chick, and frog TRPA family, whereas 2 paralogs (zTRPA1a and zTRPA1b) are present in zebrafish. We herein investigated functional differences in the 2 zebrafish TRPA1s. HEK293T cells were used as heterologous expression systems, and the sensitivities of these cells to 4 chemical irritants (allyl isothiocyanate [AITC], caffeine, auto-oxidized epigallocatechin gallate [EGCG], and hydrogen peroxide [H2O2]) were compared with Ca(2+) imaging techniques. Sensitivities to the activators for AITC, oxidized EGCG, and H2O2 were higher in cells expressing zTRPA1a than in those expressing zTRPA1b, whereas caffeine appeared to activate both cells equally. We also characterized the thermal sensitivity of Xenopus oocytes expressing each TRPA1 electrophysiologically using a 2-electrode voltage clamp. Although endogenous currents induced by a cold stimulation were observed in control oocytes in some batches, oocytes expressing zTRPA1b showed significantly stronger cold- and heat-induced responses. However, significant thermal activation was not observed in oocytes expressing zTRPA1a. The results obtained using in vitro expression systems suggest that zTRPA1a is specialized for chemical sensing, whereas zTRPA1b responds to thermal stimuli. Furthermore, characterization of the chimeric molecule of TRPA1a and 1b revealed the importance of the N-terminal region in chemical and thermal sensing by zTRPA1s.

Auto-oxidation products of epigallocatechin gallate activate TRPA1 and TRPV1 in sensory neurons.

The sensation of astringency is elicited by catechins and their polymers in wine and tea. It has been considered that catechins in green tea are unstable and auto-oxidized to induce more astringent taste. Here, we examined how mammalian transient receptor potential V1 (TRPV1) and TRPA1, which are nociceptive sensors, are activated by green tea catechins during the auto-oxidation process. Neither TRPV1 nor TRPA1 could be activated by any of the freshly prepared catechin. When one of the major catechin, epigallocatechin gallate (EGCG), was preincubated for 3h in Hank's balanced salt solution, it significantly activated both TRP channels expressed in HEK293 cells. Even after incubation, other catechins showed much less effects. Results suggest that only oxidative products of EGCG activate both TRPV1 and TRPA1. Dorsal root ganglion (DRG) sensory neurons were also activated by the incubated EGCG through TRPV1 and TRPA1 channels. Liquid chromatography-mass spectrometry revealed that theasinensins A and D are formed during incubation of EGCG. We found that purified theasinensin A activates both TRPV1 and TRPA1, and that it stimulates DRG neurons through TRPV1 and TRPA1 channels. Results suggested a possibility that TRPV1 and TRPA1 channels are involved in the sense of astringent taste of green tea.

Two single-point mutations in Ankyrin Repeat one drastically change the threshold temperature of TRPV1.

TRPV1 plays an important role in the thermosensory system; however, the mechanism controlling its heat activation property is not well understood. Here, we determine the heat activation properties of TRPV1 cloned from tailed amphibians, which prefer cooler environments, finding the threshold temperatures were approximately 10 °C lower compared with rat TRPV1 (rTRPV1). We find that two amino acid residues (Gln, Leu/Val) in the Ankyrin Repeat 1 (ANK1) region of the N-terminal domain are conserved among tailed amphibians and different from those (Arg, Lys) in rTRPV1. We observe the activation by heat in all urodelan TRPV1s is markedly elevated by substitution of these two amino acids. Conversely, reciprocal substitutions of rTRPV1 apparently lowers the high threshold temperature. Our studies demonstrate that tailed amphibians express TRPV1 with a reduced heat-activation threshold by substitution of two amino acid residues in the ANK1 region that likely contribute to cool-habitat selection.

Green tea polyphenol epigallocatechin gallate activates TRPA1 in an intestinal enteroendocrine cell line, STC-1.

A characteristic astringent taste is elicited by polyphenols. Among the polyphenols, catechins and their polymers are the most abundant polyphenols in wine and tea. A typical green tea polyphenol is epigallocatechin gallate (EGCG). Currently, the mechanism underlying the sensation of astringent taste is not well understood. We observed by calcium imaging that the mouse intestinal endocrine cell line STC-1 responds to the astringent compound, EGCG. Among major catechins of green tea, EGCG was most effective at eliciting a response in this cell line. This cellular response was not observed in HEK293T or 3T3 cells. Further analyses demonstrated that the 67-kDa laminin receptor, a known EGCG receptor, is not directly involved. The Ca(2+) response to EGCG in STC-1 cells was decreased by inhibitors of the transient receptor potential A1 (TRPA1) channel. HEK293T cells transfected with the mouse TRPA1 (mTRPA1) cDNA showed a Ca(2+) response upon application of EGCG, and their response properties were similar to those observed in STC-1 cells. These results indicate that an astringent compound, EGCG, activates the mTRPA1 in intestinal STC-1 cells. TRPA1 might play an important role in the astringency taste on the tongue.

The diversity in sensitivity of TRPA1 and TRPV1 of various animals to polyphenols.

The perception of tastes is sensed by the receptors that stimulate sensory cells. We previously reported that TRPA1 and TRPV1 channels expressed in the oral cavity of mammals, are activated by the auto-oxidized product of epigallocatechin gallate (oxiEGCG), a major astringent catechin in green tea. Here, we investigated and compared the sensitivity of TRPA1 and TRPV1 from various animals to astringent polyphenols. We selected three polyphenols, oxiEGCG, tannic acid and myricetin. HEK293T cells expressing TRPA1 or TRPV1 from mammal, bird, reptile, amphibian, and fish, were analyzed for their activation by the Ca2+-imaging. We found the apparent diversity in the polyphenol-sensitivity among various animals. Mammalian TRPs showed relatively higher sensitivity to polyphenols, and especially, human TRPA1 and TRPV1 could be activated by all of three polyphenols at 20 µM. Reptile TRP channels, however, were insensitive to any polyphenols examined. Moreover, the polyphenol-sensitivity of zebrafish TRPA1 and TRPV1 was quite different from that of medaka TRP channels. Since many polyphenols are present in plants and the sensing of polyphenols using TRP channels in the oral cavity might cause astringent taste, the observed diversity of the polyphenol-sensitivity of TRP channels might be involved in the divergence in the food habit of various animals.

Anti-tachycardia pacing for non-fast and fast ventricular tachycardias in individual Japanese patients: From Nippon-storm study.

BACKGROUND: Anti-tachycardia pacing (ATP) delivered from an implantable device is a useful tool to terminate ventricular tachycardia (VT). But its real-world efficacy for those patients having multiple VTs with varying VT rates has not been fully studied. METHODS: Using the Nippon-storm study database, efficacy of patient-by-patient basis ATP programing for Japanese patients having both non-fast (120-187 bpm) and fast VT (≥188 bpm) was assessed. According to the useful criteria of ≥50% success termination by ATP, patients were divided into three subgroups; success ≥50% for both non-fast and fast VT (both useful), ≥50% only for non-fast VT (non-fast VT useful), or ≥50% for neither non-fast nor fast VT (neither useful). RESULTS: During a median follow-up of 28 months, ATP terminated 184 of the 203 non-fast VT episodes (91%) and 86 of the 113 fast VT episodes (76%) in all 41 patients. In the patient-by-patient analysis, efficacy of ATP was not different between non-fast and fast VT in most of the patients (36/41 = 88%); 32 patients were in the both useful and four other patients in the neither useful. Neither ischemic nor non-ischemic structural heart disease was associated with the ATP efficacy, whereas LVEF more than 37.0% and non-prescribed amiodarone were characteristics of the patients classified into the both useful. CONCLUSIONS: ATP well terminated both non-fast and fast VT occurring in individual Japanese patients with various structural heart diseases in the real-world device treatment and this finding further supports ATP programing for all device tachycardia detection zones in most patients with multiple VTs.

Enhanced arrhythmogenic potential induced by renal autonomic nerve stimulation: Role of renal artery catheter ablation.

BACKGROUND: Renal artery catheter ablation has been reported as a possible therapeutic option for drug-refractory ventricular arrhythmias (VAs) associated with structural heart diseases. OBJECTIVE: To further clarify its therapeutic background, we examined the relationship between electrical nerve stimulation (ENS)-induced blood pressure (BP) elevation and occurrence of VAs by using an acute canine model of renal artery ablation. METHODS: Using a decapolar electrode catheter, ENS was successively applied from the distal, mid, and proximal segments of the renal artery in 8 beagles. The same ENS was repeated after accomplishment of radiofrequency ablation at the ostial site of the renal artery by using an irrigation catheter. RESULTS: Before ablation, ENS increased BP from 140 ± 11/77 ± 11 to 167 ± 20/98 ± 16 mm Hg and heart rate from 100 ± 21 to 131±33 beats/min as well as induced VAs in 20 of the 45 ENS applications. Occurrence of VAs was associated with a greater magnitude of sympathetic nerve augmentation, and VAs were more frequently observed by ENS at the distal (67%) rather than mid/proximal segments of the renal artery (33%). Renal artery ablation was accomplished without any angiographic stenosis, and ENS-induced BP elevation, heart rate acceleration, and VAs occurrence were attenuated not only at the close segment (proximal) but also at the remote segments (mid/distal) of the renal artery. CONCLUSION: The renal autonomic nerves are considered as one of the therapeutic targets for suppression of frequent VAs because its activation has arrhythmogenic potential and induces premature ventricular beats.