Comparison of the left ventricular dyssynchrony between stylet-driven and lumen-less lead technique in left bundle branch area pacing using myocardial perfusion scintigraphy.

Background: Left bundle branch area pacing (LBBAP) has emerged as a novel physiological pacing method to reduce left ventricular (LV) dyssynchrony due to ventricular pacing. Only lumen-less pacing leads (LLLs) with fixed helixes could achieve LBBAP previously, but recently, LBBAP has been performed using stylet-driven leads (SDLs). This study aimed to evaluate the LV dyssynchrony between SDLs and LLLs techniques in LBBAP. Methods: We retrospectively evaluated patients who underwent LBBAP with either SDLs or LLLs. We compared both groups' electrocardiogram (ECG) findings and LV dyssynchrony parameters derived from myocardial perfusion scintigraphy. LV dyssynchrony parameters consisted of phase analysis and regional wall motion analysis. We evaluated bandwidth, phase standard deviation (PSD), and entropy in the phase analysis. The time to the end-systolic frame (TES) was calculated in regional wall motion analysis using single-photon emission computed tomography (SPECT). We also evaluated the maximum differences between segmental TES (MDTES), the standard deviation of TES (SDTES), and the difference in the TES between the lateral wall and septum (DTES-LS). Results: In total, 97 patients were enrolled. The success rate of LBBAP did not differ between the groups [SDLs: 47/48 patients (98%) vs. LLLs: 47/51 patients (92%), P=0.36]. The paced QRS duration and the stimulus to the peak LV activation time (stim-LVAT) also did not differ between SDL and LLL groups (122±10 vs. 119±12 ms, P=0.206; 69±12 vs. 66±13 ms, P=0.31, respectively). There were no differences in bandwidth, PSD, and entropy between SDL and LLL groups (73°±37° vs. 86°±47°, P=0.18; 19°±8.5° vs. 21°±9.7°, P=0.19; 0.57±0.08 vs. 0.59±0.08, P=0.17, respectively). The regional wall motion analysis parameters MDTES, SDTES, and DTES-LS also did not differ between SDL and LLL groups (19%±10% vs. 20%±10%, P=0.885; 5.0%±2.5% vs. 5.0%±2.5%, P=0.995; 5.0%±3.7% vs. 4.8%±4.2%, P=0.78, respectively). Conclusions: LBBAP using SDLs was comparable to LV electrical and mechanical synchrony with LLLs.

Draft Genome Sequence of Aduncisulcus paluster, a Free-Living Microaerophilic Eukaryote Belonging to the Fornicata.

Aduncisulcus paluster is a free-living, unicellular flagellate belonging to the eukaryotic lineage Fornicata, which includes free-living and commensal/parasitic organisms. Here, we report the draft genome sequence of A. paluster, which provides clues for elucidating the adaptation to microaerophilic/anaerobic environments and the transition between free-living and commensal/parasitic lifestyles in Fornicata.

Assessing cardiac mechanical dyssynchrony in left bundle branch area pacing and right ventricular septal pacing using myocardial perfusion scintigraphy in the acute phase of pacemaker implantation.

INTRODUCTION: Left bundle branch area pacing (LBBAP) has recently been reported to be a new, clinically feasible and safe physiological pacing strategy. The present study aims to investigate the usefulness of LBBAP in reducing mechanical dyssynchrony compared with right ventricular septal pacing (RVSP). METHODS AND RESULTS: A total of 39 LBBAP patients, 42 RVSP patients, and 93 healthy control participants were retrospectively evaluated. We compared phase analysis- (bandwidth, phase standard deviation [PSD], entropy) and regional wall motion analysis parameters. Wall motion analysis parameters included the time to the end-systolic frame (TES) assessed using single-photon emission computed tomography analysis. The maximum differences between segmental TES (MDTES), the standard deviation of TES (SDTES), and the TES difference between the lateral and septal segments (DTES-LS) were obtained. All phase analysis parameters were significantly smaller in the LBBAP group than in the RVSP group (bandwidth: LBBAP, 74 ± 31° vs. RVSP, 102 ± 59°, p = .009; PSD: LBBAP, 19 ± 6.7° vs. RVSP, 26 ± 15°, p = .007; entropy: LBBAP, 0.57 ± 0.07 vs. RVSP, 0.62 ± 0.11 p = .009). The regional wall motion analysis parameters were also smaller in the LBBAP group than in the RVSP group (MDTES:LBBAP, 17 ± 7.1% vs. RVSP, 25 ± 14%, p = .004; SDTES:LBBAP, 4.5 ± 1.7% vs. RVSP, 6.0 ± 3.5%, p = .015; DTES-LS: LBBAP, 4.1 ± 3.4% vs. RVSP, 7.1 ± 5.4%, p = .004). All phase analysis and wall motion analysis parameters were same in the LBBAP and control groups. CONCLUSION: LBBAP may reduce mechanical dyssynchrony and achieve greater physiological ventricular activation than RVSP.

Impact of the Degree of Wire Bias in the Vessel's Healthy Portion on Coronary Perivascular Trauma in Rotational Atherectomy.

BACKGROUND: In rotational atherectomy (RA), the risk of coronary perforation is considered to increase when the wire is in contact with the healthy portion of the vessel. However, the relationship between the extent of wire bias in the healthy portion of the vessel and the risk of coronary perivascular trauma (CPT) has not been reported. METHODS: We examined 90 consecutive cases wherein intravascular ultrasound (IVUS) was performed before and after RA. The IVUS catheter in contact with the healthy region of the vessel was defined as the healthy portion wire bias (HWB), of which we measured the bias diameter, defined as the media-to-media length between the site where the IVUS catheter was in contact and the opposite side of the vessel. The bias ratio was defined as the ratio of the bias diameter to the short diameter at the region where the wire bias was the strongest. The relationship between the bias ratio and the CPT risk was evaluated. RESULTS: CPT was significantly higher in the HWB group than in the non-HWB group (9% vs. 0%, P = 0.048). In the HWB group, the bias ratio was significantly greater in the CPT group than in the non-CPT group (1.31 ±â€¯0.09 vs. 1.06 ±â€¯0.06; P < 0.0001). The cutoff value of the bias ratio for CPT was 1.2, which was the maximum value of the sum of sensitivity 100% and specificity 97%. CONCLUSIONS: Lesions without HWB had no CPT. CPT risk increased when the bias ratio exceeded 1.2.

An Autopsy Case of Antibody-negative Immune-mediated Necrotizing Myopathy with Severe Cardiac Involvement.

A 41-year-old man was admitted with a chief complaint of dyspnea. Echocardiography showed diffuse severe hypokinesis in the left ventricle. Although his heart failure improved, high creatine kinase levels persisted. A muscle biopsy of the biceps brachii showed necrotic and regenerating fibers along with positive findings for major histocompatibility complex class I and membrane attack complex. He was diagnosed with antibody-negative immune-mediated necrotizing myopathy (IMNM). Steroid therapy was started, but he died due to ventricular fibrillation. Autopsy findings revealed CD68-positive macrophages in the myocardium and quadriceps. To our knowledge, this is the first case of antibody-negative IMNM with cardiac involvement.

Growth of microorganisms in total parenteral nutrition solutions containing lipid.

BACKGROUND: To identify the microorganisms that can grow rapidly in total parenteral nutrition (TPN) solutions, we investigated the growth of the major causes of catheter-related blood stream infection (Staphylococcus aureus, Serratia marcescens, Bacillus cereus, and Candida albicans) in TPN solutions containing lipid. METHODS: The pH value of a TPN solution containing lipid (pH 6.0, containing 20 ppm of NaHSO(3)) was adjusted by the addition of HCl to 5.7, 5.4, or 4.9. The pH value of another TPN solution (pH5.5, containing 400 ppm of NaHSO(3)) was adjusted by the addition of NaOH to 5.9, 6.3, or 6.8. A specific number of each microorganism was added to 10 mL of each test solution and incubated at room temperature. The number of microorganisms was counted as colony forming units at 0, 24, and 48 hrs later. RESULTS: C albicans increased similarly at any pH values in the TPN solution. The bacterial species also increased rapidly at pH6.0 in the solution containing 20 ppm of NaHSO(3), but growth was suppressed as the pH value was reduced, with growth halted at pH4.9. However, these bacterial species did not increase, even at pH5.9, in the other solution containing 400 ppm of NaHSO(3). CONCLUSIONS: These results suggest that Candida species can grow rapidly in almost all TPN solutions regardless of the acidity, lipid, and NaHSO(3); also, some bacterial species may grow in TPN solutions containing lipid unless the pH value is 5.0 or less. Therefore, each TPN solution should be examined whether or not the bacterial species can proliferate.

Dynamics of thin-filament activation in rabbit skeletal muscle fibers examined by time-resolved x-ray diffraction.

By using skinned-rabbit skeletal muscle fibers, the time courses of changes of thin filament-based x-ray reflections were followed at a 3.4-ms time resolution during thin-filament activation. To discriminate between the effects of calcium binding and myosin binding on thin-filament activity, measurements were performed after caged-calcium photolysis in fibers with full-filament or no-filament overlap, or during force recovery after a quick release. All three reflections examined, i.e., the second actin layer line (second ALL, reporting the tropomyosin movement), the sixth ALL (reporting actin structural change), and the meridional troponin reflections, exhibited calcium-induced and myosin-induced components, but their rate constants and polarities were different. Generally, calcium-induced components exhibited fast rate constants (>100 s(-1)). The myosin-induced components of the second ALL had a rate constant similar to that of the force (7-10 s(-1)), but that of the sixth ALL was apparently faster. The myosin-induced component of troponin reflection was the only one with negative polarity, and was too slow to be analyzed with this protocol. The results suggest that the three regulation-related proteins change their structures with different rate constants, and the significance of these findings is discussed in the context of a cooperative thin-filament activation mechanism.

Diversity of structural behavior in vertebrate conventional myosins complexed with actin.

Low-resolution three-dimensional structures of acto-myosin subfragment-1 (S1) complexes were retrieved from X-ray fiber diffraction patterns, recorded either in the presence or absence of ADP. The S1 was obtained from various myosin-II isoforms from vertebrates, including rabbit fast-skeletal and cardiac, chicken smooth and human non-muscle IIA and IIB species, and was diffused into an array of overstretched, skinned skeletal muscle fibers. The S1 attached to the exposed actin filaments according to their helical symmetry. Upon addition of ADP, the diffraction patterns from acto-S1 showed an increasing magnitude of response in the order as listed above, with features of a lateral compression of the whole diffraction pattern (indicative of increased radius of the acto-S1 complex) and an enhancement of the fifth layer-line reflection. The structure retrieval indicates that these changes are mainly due to the swing of the light chain (LC) domain in the direction consistent with the cryo-electron microscopic results. In the non-muscle isoforms, the swing is large enough to affect the manner of quasi-crystal packing of the S1-decorated actin filaments and their lattice dimension, with a small change in the twist of actin filaments. Variations also exist in the behavior of the 50K-cleft, which apparently opens upon addition of ADP to the non-muscle isoforms but not to other isoforms. The fast-skeletal S1 remains as the only isoform that does not clearly exhibit either of the structural changes. The results indicate that the "conventional" myosin-II isoforms exhibit a wide variety of structural behavior, possibly depending on their functions and/or the history of molecular evolution.

Significance of kinetic degrees of freedom in operation of the actomyosin motor.

The actomyosin motor as a principal functional component of cell motility is highly coordinated in regulating the participating molecular components. At the same time, it has to be flexible and plastic enough to accommodate itself to a wide variety of operational conditions. We prepared two different types of actomyosin systems. One is a natural intact actomyosin system with no artificial constraint on the kinetic degrees of freedom of the actin filaments, and the other is a regulated one with actin filaments supplemented by intra- and intermolecular crosslinking to suppress the kinetic degrees of freedom to a certain extent. Crosslinked actomyosin systems were found to remain almost insensitive to calcium regulation even when intact troponin-tropomyosin regulatory component was incorporated. Both the ATPase and the motile activities of the actin filaments sliding on myosin molecules were markedly lowered by the crosslinking. In contrast, once the crosslinking was cleaved, both properties returned to the normal as with intact actomyosin systems.

Intensity of X-ray reflections from skeletal muscle thin filaments partially occupied with myosin heads: effect of cooperative binding.

For quantitative analysis of contractile proteins of muscle by means of X-ray diffraction, it is important to know how the intensities of individual reflections are related to the number of diffracting objects, i.e., the amount of constituent contractile protein in the muscle cell. Here we diffused various amounts of exogenous myosin subfragment-1 (S1) into overstretched skinned skeletal muscle fibers, either in the presence or absence of Ca2+ , and derived the relationship between the S1 content and the intensities of reflections arising from the S1. In theory, the intensities should be proportional to the square of the S1 content (square law). However, the intensity-content relation deviated systematically from the square law as the S1 content was lowered, and it was better described as a linear function at the lower end of the S1 contents (<20% of saturation level). Model calculations show that the way of deviation is explained by the cooperative manner of S1 binding to the regulated thin filament.

Structural transients of contractile proteins upon sudden ATP liberation in skeletal muscle fibers.

Structural changes of contractile proteins were examined by millisecond time-resolved two-dimensional x-ray diffraction recordings during relaxation of skinned skeletal muscle fibers from rigor after caged ATP photolysis. It is known that the initial dissociation of the rigor actomyosin complex is followed by a period of transient active contraction, which is markedly prolonged in the presence of ADP by a mechanism yet to be clarified. Both single-headed (overstretched muscle fibers with exogenous myosin subfragment-1) and two-headed (fibers with full filament overlap) preparations were used. Analyses of various actin-based layer line reflections from both specimens showed the following: 1), The dissociation of the rigor actomyosin complex was fast and only modestly decelerated by ADP and occurred in a single exponential manner without passing through any detectable transitory state. Its ADP sensitivity was greater in the two-headed preparation but fell short of explaining the large ADP effect on the transient active contraction. 2), The decay of the activated state of the thin filament followed the time course of tension more closely in an ADP-dependent manner. These results suggest that the interplay between the reattached active myosin heads and the thin filament is responsible for the prolonged active contraction in the presence of ADP.

Thymol: a classical small-molecule compound that has a dual effect (potentiating and inhibitory) on myosin.

The effect of thymol on the ATPase activity of myosin subfragment-1 (S1) and on the contractile properties of skinned skeletal muscle fibers was studied. At concentrations of 1.5-2 mM, thymol activated the S1 ATPase substantially and the actin-activated S1 ATPase modestly. At the same concentrations, the isometric force of skinned skeletal muscle fibers was modestly suppressed (11% at 2 mM). However, the kinetic parameters of contraction were suppressed more: the velocity of shortening and the rate of force redevelopment after shortening were suppressed by 43% and 31% at 2 mM, respectively. Thus, among other small-molecule inhibitors, thymol is unique in that it has opposite effects on the enzymatic activity and kinetic parameters of contraction. Thymol may serve as a potent tool for studying the mechanism of coupling between the ATPase reaction and contraction in muscle.

Mechanism for the phase transition of a genetically engineered elastin model peptide (VPGIG)40 in aqueous solution.

The concentration dependence of the pressure- and temperature-induced cloud point transition (Pc and Tc, respectively) of aqueous solutions of an elastin-like polypeptide with a repeating pentapeptide Val-Pro-Gly-Ile-Gly sequence (MGLDGSMG(VPGIG)40VPLE) was investigated by using apparent light scattering, differential scanning calorimetry, and circular dichroism methods. In addition, the effects of salts and surfactants on these properties were investigated. The Pc and Tc of the present peptide in aqueous solution were strongly concentration dependent. The calorimetric measurements showed that the enthalpy of transitions was 300-400 kJ/mol, i.e., 7-10 kJ/mol per VPGIG pentamer. The Tc of the (VPGIG)40 solution was highly affected by the addition of inert salts or SDS. The effects of salts were consistent with those observed in the lyotropic series or Hoffmeister series. The CD spectrum at low peptide concentrations indicated that the present peptide forms type II beta-turn-like structure(s) at higher temperatures, but the temperature dependence of random coil diminishment (195 nm) and beta-turn formation (210 nm) were not exactly coincident. A hypothetical mechanism of the (VPGIG)40 phase transition that could account for these observations was postulated. Observations suggest that the temperature-responsive properties of the elastin model peptides occur via a mechanism involving conformational change-association-aggregation and that the first two are strongly interactive.