Cardiac magnetic resonance imaging for preprocedural planning of percutaneous left atrial appendage closure

IntroductionPercutaneous closure of the left atrial appendage (LAA) facilitates stroke prevention in patients with atrial fibrillation. Optimal device selection and positioning are often challenging due to highly variable LAA shape and dimension and thus require accurate assessment of the respective anatomy. Transesophageal echocardiography (TEE) and x-ray fluoroscopy (XR) represent the gold standard imaging techniques. However, device underestimation has frequently been observed. Assessment based on 3-dimensional computer tomography (CTA) has been reported as more accurate but increases radiation and contrast agent burden. In this study, the use of non-contrast-enhanced cardiac magnetic resonance imaging (CMR) to support preprocedural planning for LAA closure (LAAc) was investigated.MethodsCMR was performed in thirteen patients prior to LAAc. Based on the 3-dimensional CMR image data, the dimensions of the LAA were quantified and optimal C-arm angulations were determined and compared to periprocedural data. Quantitative figures used for evaluation of the technique comprised the maximum diameter, the diameter derived from perimeter and the area of the landing zone of the LAA.ResultsPerimeter- and area-based diameters derived from preprocedural CMR showed excellent congruency compared to those measured periprocedurally by XR, whereas the respective maximum diameter resulted in significant overestimation (p < 0.05). Compared to TEE assessment, CMR-derived diameters resulted in significantly larger dimensions (p < 0.05). The deviation of the maximum diameter to the diameters measured by XR and TEE correlated well with the ovality of the LAA. C-arm angulations used during the procedures were in agreement with those determined by CMR in case of circular LAA.DiscussionThis small pilot study demonstrates the potential of non-contrast-enhanced CMR to support preprocedural planning of LAAc. Diameter measurements based on LAA area and perimeter correlated well with the actual device selection parameters. CMR-derived determination of landing zones facilitated accurate C-arm angulation for optimal device positioning

Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II

The tail of yeast myosin II is localized to the division site by two distinct molecular pathways and sufficient for promoting actomyosin ring assembly, furrow ingression, and guidance in ECM remodeling

Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae

Cytokinesis requires coordination of actomyosin ring (AMR) contraction with rearrangements of the plasma membrane and extracellular matrix. In Saccharomyces cerevisiae, new membrane, the chitin synthase Chs2 (which forms the primary septum [PS]), and the protein Inn1 are all delivered to the division site upon mitotic exit even when the AMR is absent. Inn1 is essential for PS formation but not for Chs2 localization. The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Δ cells). The Inn1 N terminus resembles C2 domains but does not appear to bind phospholipids; nonetheless, when overexpressed or fused to Hof1, it can provide Inn1 function even in the absence of the AMR. Thus, Inn1 and Cyk3 appear to cooperate in activating Chs2 for PS formation, which allows coordination of AMR contraction with ingression of the cleavage furrow

Shs1 Plays Separable Roles in Septin Organization and Cytokinesis in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, five septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1/Sep7) form the septin ring at the bud neck during vegetative growth. We show here that disruption of SHS1 caused cold-sensitive growth in the W303 background, with cells arrested in chains, indicative of a cytokinesis defect. Surprisingly, the other four septins appeared to form an apparently normal septin ring in shs1Δ cells grown under the restrictive condition. We found that Myo1 and Iqg1, two components of the actomyosin contractile ring, and Cyk3, a component of the septum formation, were either delocalized or mislocalized in shs1Δ cells, suggesting that Shs1 plays supportive roles in cytokinesis. We also found that deletion of SHS1 enhanced or suppressed the septin defect in cdc10Δ and cdc11Δ cells, respectively, suggesting that Shs1 is involved in septin organization, exerting different effects on septin-ring assembly, depending on the composition of the septin subunits. Furthermore, we constructed an shs1-100c allele that lacks the coding sequence for the C-terminal 32 amino acids. This allele still displayed the genetic interactions with the septin mutants, but did not show cytokinesis defects as described above, suggesting that the roles of Shs1 in septin organization and cytokinesis are separable

Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A

Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs

The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats

Background. Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats. Methods. Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF). CE, CF, and CEF rats were treated orally with enalapril maleate, folic acid, or enalapril maleate and folic acid tablets, respectively, for 5 days. CIN was induced in all groups followed by analyzed biochemical parameters, oxidative stress markers, endothelial dysfunction parameters, renal histopathology, and TUNEL staining. Results. Serum creatinine, blood urea nitrogen, and malondialdehyde levels were lower in the CEF group than in the C group. Homocysteine, superoxide dismutase, glutathione peroxidase, and nitric oxide levels were higher in the CEF group than in the C group. Histopathology scores and percentage of apoptotic kidney cells in the CEF group were significantly decreased compared with those in the C group. Conclusions. These results suggest that enalapril maleate and folic acid tablets have a protective effect against CIN in diabetic rats