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Auditory feedback may provide the nervous system with valuable temporal (e. g., footstep sounds) and spatial (e.g., external reference sounds) information that can assist in the control of upright walking. As such, hearing loss may directly contribute to declines in mobility among older adults. Our purpose was to examine the impact of auditory feedback on the control of walking in older adults. Twenty older adults (65–86 years) with no diagnosed hearing loss walked on a treadmill for three sound conditions: Baseline, Ear Plugs, and White Noise. We hypothesized that in response to reduced temporal auditory feedback during the Ear Plugs and White Noise conditions, participants would adapt shorter and faster steps that are traditionally believed to increase mechanical stability. This hypothesis was not supported. Interestingly, we observed increases in step length (p = 0.047) and step time (p = 0.026) during the Ear Plugs condition vs. Baseline. Taking longer steps during the Ear Plugs condition may have increased ground reaction forces, thus allowing participants to sense footsteps via an occlusion effect. As a follow-up, we performed a Pearson's correlation relating the step length increase during the Ear Plugs condition to participants' scores on a clinical walking balance test, the Functional Gait Assessment. We found a moderate negative relationship (rho = −0.44, p = 0.055), indicating that participants with worse balance made the greatest increases in step length during the Ear Plugs condition. This trend suggests that participants may have actively sought auditory feedback with longer steps, sacrificing a more mechanically stable stepping pattern. We also hypothesized that reduced spatial localization feedback during the Ear Plugs and White Noise conditions would decrease control of center of mass (COM) dynamics, resulting in an increase in lateral COM excursion, lateral margin of stability, and maximum Lyapunov exponent. However, we found no main effects of auditory feedback on these metrics (p = 0.580, p = 0.896, and p = 0.056, respectively). Overall, these results suggest that during a steady-state walking task, healthy older adults can maintain walking control without auditory feedback. However, increases in step length observed during the Ear Plugs condition suggest that temporal auditory cues provide locomotor feedback that becomes increasingly valuable as balance deteriorates with age.

Purpose: To determine whether the introduction of a policy of adjunctive stent insertion based on preoperative CT assessment or completion angiography reduced the incidence of limb occlusion after stent-graft implantation for endovascular aneurysm repair (EVAR). Methods: A tertiary referral unit's endovascular database was retrospectively interrogated to compare the incidence of endograft limb occlusion in Zenith grafts following the introduction of a policy of selective adjunctive stent insertion. Group A included 288 limbs at risk in 146 patients (134 men; mean age 74+/-8 years) treated prior to August 2005 in whom adjunctive stents were inserted on an ad hoc basis only. Group B included 293 limbs at risk in 149 patients (127 men; mean age 76+/-7 years) treated after this date in whom a more aggressive adjunctive stenting strategy was adopted. Kaplan-Meier analysis was employed to compare outcomes. Results: In total, 295 patients underwent EVAR involving 581 iliac vessels, of which 11 (1.8%) occluded at a median of 24 months (0-27). Of 65 limbs extended into the external iliac segment, 5 (7.6%) subsequently occluded; in the remaining 516 limbs, there were 6 (1.1%) occlusions (p = 0.004). Across the study group, 38 (6.5%) adjunctive stents were deployed in limbs deemed at risk; 1 (2.6%) of these occluded. In the remaining 543 unstented limbs, 10 (1.8%) occlusions occurred (p = 0.15). There were 11 occlusions in group A, in which 5 (1.7%) adjunctive stents had been deployed, but none in group B, which had received 33 (11.2%) stents (p<0.0001). Kaplan-Meier survival curves identified primary patency rates at 36 months of 96% and 100%, respectively (p = 0.001). Conclusion: Adjunctive stenting significantly reduces the risk of postoperative stent-graft limb occlusion without obvious compromise to the aneurysm repair. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether fenestrated stent-grafts provide better stability to resist migration than standard non-fenestrated stent-grafts.Methods: Truncated fenestrated stent-grafts with a single fenestration were deployed in bovine aortic segments with a side branch. Balloon-expandable stents were then delivered into the branches. Similarly, standard stent-grafts of the same dimensions were deployed for comparison. The aorta was pressurized to achieve stent-graft oversizing of 5%, 10%, or 20%. The force required to cause distal migration was recorded by a digital force gauge attached to the stent-graft.Results: Displacement of the stent-grafts occurred in 2 distinct phases: an initial yield during which the barbs embedded in the aortic wall and a final displacement leading to significant migration and dislodgement of the device. The displacement force that initiated each phase was dependent upon the degree of oversizing of the stent-graft relative to the aortic diameter. For 5%, 10%, and 20% oversizing, the mean displacement forces in the initial displacement phase were 3.39+/-0.37, 4.32+/-0.63, and 7.69+/-1.18 N, respectively, in non-fenestrated grafts and 10.48+/-1.23, 11.45+/-1.48, 12.12+/-1.42 N in fenestrated grafts. The displacement forces in the final displacement phase were 8.10+/-0.92, 10.76+/-1.74, and 16.82+/-0.92 N for non-fenestrated and 22.56+/-1.60, 28.24+/-1.56, and 33.01+/-1.75 N for fenestrated stent-grafts. The differences in displacement forces between standard and fenestrated stent-grafts were significant for both phases (p<0.001) at all oversizing levels.Conclusion: Improvement in fixation strength was noted with increasing stent-graft oversizing of up to 20%. Fenestrated stent-grafts offer higher ultimate fixation compared to standard devices. However, the ultimate fixation strength was not recruited until an initial phase of short migration occurred as the barbs engaged. While this movement is inconsequential with standard stent-grafts, it has the potential to crush the stents placed into aortic side branches with fenestrated endografts. [ABSTRACT FROM AUTHOR]

Diastolic Ca 2+ leak due to cardiac ryanodine receptor (RyR2) hyperactivity has been widely documented in chronic ischemic heart disease (CIHD) and may contribute to ventricular tachycardia (VT) risk and progressive left-ventricular (LV) remodeling. Here we test the hypothesis that targeting RyR2 hyperactivity can suppress VT inducibility and progressive heart failure in CIHD by the RyR2 inhibitor dantrolene. METHODS AND RESULTS: CIHD was induced in C57BL/6 J mice by left coronary artery ligation. Four weeks later, mice were randomized to either acute or chronic (6 weeks via implanted osmotic pump) treatment with dantrolene or vehicle. VT inducibility was assessed by programmed stimulation in vivo and in isolated hearts. Electrical substrate remodeling was assessed by optical mapping. Ca 2+ sparks and spontaneous Ca 2+ releases were measured in isolated cardiomyocytes. Cardiac remodeling was quantified by histology and qRT-PCR. Cardiac function and contractility were measured using echocardiography. Compared to vehicle, acute dantrolene treatment reduced VT inducibility. Optical mapping demonstrated reentrant VT prevention by dantrolene, which normalized the shortened refractory period (VERP) and prolonged action potential duration (APD), preventing APD alternans. In single CIHD cardiomyocytes, dantrolene normalized RyR2 hyperactivity and prevented spontaneous intracellular Ca 2+ release. Chronic dantrolene treatment not only reduced VT inducibility but also reduced peri-infarct fibrosis and prevented further progression of LV dysfunction in CIHD mice. CONCLUSIONS: RyR2 hyperactivity plays a mechanistic role for VT risk, post-infarct remodeling, and contractile dysfunction in CIHD mice. Our data provide proof of concept for the anti-arrhythmic and anti-remodeling efficacy of dantrolene in CIHD., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Recently, our laboratory presented functional and molecular evidence for the presence of 2 competing sinoatrial node (SAN) pacemakers in healthy human and rat hearts. Anatomically localized near the superior vena cava and inferior vena cava, the superior and inferior SANs (sSAN and iSAN, respectively) preferentially control fast and slow normal heart rates. However, only 1 dominant pacemaker, primarily the sSAN, was functional in the failing rat heart with hypertrophic cardiomyopathy., Objectives: This study aimed to determine the transcriptional basis of functional silencing of 1 of 2 dominant pacemakers in failing rat hearts., Methods: Ascending aortic constriction was performed on 1-week-old male Sprague-Dawley rat pups to induce left ventricular hypertrophy and heart failure. The dominant pacemaker was anatomically mapped in adult (10-12 weeks old) healthy and failing rat hearts using optical mapping in isolated right atrial tissue preparations. RNA sequencing was used to identify regional sSAN/iSAN gene expression differences between healthy and failing rat hearts., Results: In all failing rat hearts optically mapped in this study (n = 4), only the sSAN pacemaker was functional, while the iSAN was silent. Compared to healthy rat hearts, a total of 3,640 genes were downregulated, and 4,518 genes were upregulated in failing rat hearts. The functional quiescence of the iSAN in these failing rat hearts may be explained by their downregulation of sodium, potassium, and calcium ion channels as well as their downregulation of specific structural genes, including ankyrin, titin, and myosin heavy chain. Moreover, the iSAN showed predominant downregulation of several key transcription factors such as Tbx5, Tbx3, Shox2, and Smad9., Conclusions: Pressure-overload-induced heart failure resulted in significant downregulation of critical transcription factors, ion channels, and structural transcripts of the iSAN, which could explain the functional silencing of the iSAN in failing rat hearts., Competing Interests: Funding Support and Author Disclosures This project was supported by the National Institutes of Health (NIH) Stimulating Peripheral Activity to Relieve Conditions (SPARC) grant 3OT2OD023848, NIH grant R21 HL152324; and American Heart Association 2019 CENTER grant SCD SFRN. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Monitoring and control of cardiac function are critical for investigation of cardiovascular pathophysiology and developing life-saving therapies. However, chronic stimulation of the heart in freely moving small animal subjects, which offer a variety of genotypes and phenotypes, is currently difficult. Specifically, real-time control of cardiac function with high spatial and temporal resolution is currently not possible. Here, we introduce a wireless battery-free device with on-board computation for real-time cardiac control with multisite stimulation enabling optogenetic modulation of the entire rodent heart. Seamless integration of the biointerface with the heart is enabled by machine learning-guided design of ultrathin arrays. Long-term pacing, recording, and on-board computation are demonstrated in freely moving animals. This device class enables new heart failure models and offers a platform to test real-time therapeutic paradigms over chronic time scales by providing means to control cardiac function continuously over the lifetime of the subject.

Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/ LUMA ). The study aimed to investigate biological roles of TMEM43 through genetic regulation, gene pathways and gene networks, candidate interacting genes, and up- or downstream regulators. Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) were applied for genetic correlation, functional enrichment, and coexpression network analysis using systems genetics approach. The results were validated in a newly created knock-in Tmem43 -S358L mutation mouse model (Tmem43 S358L ) that displayed signs of cardiac dysfunction, resembling ARVC5 phenotype seen in humans. We found high Tmem43 levels among BXDs with broad variability in expression. Expression of Tmem43 highly negatively correlated with heart mass and heart rate among BXDs, whereas levels of Tmem43 highly positively correlated with plasma high-density lipoproteins (HDL). Through finding differentially expressed genes (DEGs) between Tmem43 S358L mutant and wild-type (Tmem43 WT ) lines, 18 pathways (out of 42 found in BXDs GRP) that are involved in ARVC, hypertrophic cardiomyopathy, dilated cardiomyopathy, nonalcoholic fatty liver disease, Alzheimer's disease, Parkinson's disease, and Huntington's disease were verified. We further constructed Tmem43 -mediated gene network, in which Ctnna1 , Adcy6 , Gnas , Ndufs6 , and Uqcrc2 were significantly altered in Tmem43 S358L mice versus Tmem43 WT controls. Our study defined the importance of Tmem43 for cardiac- and metabolism-related pathways, suggesting that cardiovascular disease-relevant risk factors may also increase risk of metabolic and neurodegenerative diseases via TMEM43 -mediated pathways.

Introduction: In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?', Methods and Analysis: UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years., Ethics and Dissemination: The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences., Trial Registration Number: ISRCTN85731188., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Optogenetic technology provides researchers with spatiotemporally precise tools for stimulation, sensing, and analysis of function in cells, tissues, and organs. These tools can offer low-energy and localized approaches due to the use of the transgenically expressed light gated cation channel Channelrhodopsin-2 (ChR2). While the field began with many neurobiological accomplishments it has also evolved exceptionally well in animal cardiac research, both in vitro and in vivo . Implantable optical devices are being extensively developed to study particular electrophysiological phenomena with the precise control that optogenetics provides. In this review, we highlight recent advances in novel implantable optogenetic devices and their feasibility in cardiac research. Furthermore, we also emphasize the difficulties in translating this technology toward clinical applications and discuss potential solutions for successful clinical translation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Madrid, Brennan, Yin, Knight and Efimov.)

Background: In FEVAR, visceral stents provide continuity and maintain perfusion between the main body of the stent and the respective visceral artery. The aim of this study was to characterise the incidence and mode of visceral stent failure (type Ic endoleak, type IIIa endoleak, stenosis/kink, fracture, crush and occlusion) after FEVAR in a large cohort of patients at a high-volume centre., Methods: A retrospective review of visceral stents placed during FEVAR over 15 years (February 2003-December 2018) was performed. Kaplan-Meier analyses of freedom from visceral stent-related complications were performed. The outcomes between graft configurations of varying complexity were compared, as were the outcomes of different stent types and different visceral vessels., Results: Visceral stent complications occurred in 47/236 patients (19.9%) and 54/653 stents (8.3%). Median follow up was 3.7 years (IQR 1.7-5.3 years). There was no difference in visceral stent complication rate between renal, SMA and coeliac arteries. Visceral stent complications were more frequent in more complex grafts compared to less complex grafts. Visceral stent complications were more frequent in uncovered stents compared to covered stents. Visceral stent-related endoleaks (type Ic and type IIIa) occurred exclusively around renal artery stents. The most common modes of failure with SMA stents were kinking and fracture, whereas with coeliac artery stents it was external crush., Conclusion: Visceral stent complications after FEVAR are common and merit continued and close long-term surveillance. The mode of visceral stent failure varies across the vessels in which the stents are located., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objectives: This study sought to investigate the shift of leading pacemaker locations in healthy and failing mammalian hearts over the entire range of physiological heart rates (HRs), and to molecularly characterize spatial regions of spontaneous activity., Background: A normal heartbeat originates as an action potential in a group of pacemaker cells known as the sinoatrial node (SAN), located near the superior vena cava. HRs and the anatomical site of origin of pacemaker activity in the adult heart are known to dynamically change in response to various physiological inputs, yet the mechanism of this pacemaker shift is not well understood., Methods: Optical mapping was applied to ex vivo rat and human isolated right atrial tissues, and HRs were modulated with acetylcholine and isoproterenol. RNA sequencing was performed on tissue areas that elicited spontaneous activity, and comparisons were made to neighboring myocardial tissues., Results: Functional and molecular evidence identified and confirmed the presence of 2 competing right atrial pacemakers localized near the superior vena cava and the inferior vena cava-the superior SAN (sSAN) and inferior SAN (iSAN), respectively-which preferentially control the fast and slow HRs. Both of these regions were evident in non-failing rat and human hearts and maintained spontaneous activity in the rat heart when physically separated from one another. Molecular analysis of these 2 pacemaker regions revealed unique but similar transcriptional profiles, suggesting iSAN dominance when the sSAN is silent., Conclusions: The presence of 2 spatially distinct dominant pacemakers, sSAN and iSAN, in the mammalian heart clarifies previous identification of migrating pacemakers and corresponding changes in P-wave morphology in mammalian species., Competing Interests: Author Disclosures Drs. Brennan and Efimov were supported by National Institutes of Health Stimulating Peripheral Activity to Relieve Conditions (SPARC) grant 3OT2OD023848. Drs. Chen and Peng were supported by National Institutes of Health grants AI121080 and AI139874. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: ZO-1 (Zona occludens 1), encoded by the tight junction protein 1 ( TJP1 ) gene, is a regulator of paracellular permeability in epithelia and endothelia. ZO-1 interacts with the actin cytoskeleton, gap, and adherens junction proteins and localizes to intercalated discs in cardiomyocytes. However, the contribution of ZO-1 to cardiac physiology remains poorly defined., Objective: We aim to determine the role of ZO-1 in cardiac function., Methods and Results: Inducible cardiomyocyte-specific Tjp1 deletion mice ( Tjp1 fl/fl ; Myh6 Cre/Esr1* ) were generated by crossing the Tjp1 floxed mice and Myh6 Cre/Esr1* transgenic mice. Tamoxifen-induced loss of ZO-1 led to atrioventricular (AV) block without changes in heart rate, as measured by ECG and ex vivo optical mapping. Mice with tamoxifen-induced conduction system-specific deletion of Tjp1 ( Tjp1 fl/fl ; Hcn4 CreERt2 ) developed AV block while tamoxifen-induced conduction system deletion of Tjp1 distal to the AV node ( Tjp1 fl/fl ; Kcne1 CreERt2 ) did not demonstrate conduction defects. Western blot and immunostaining analyses of AV nodes showed that ZO-1 loss decreased Cx (connexin) 40 expression and intercalated disc localization. Consistent with the mouse model study, immunohistochemical staining showed that ZO-1 is abundantly expressed in the human AV node and colocalizes with Cx40. Ventricular conduction was not altered despite decreased localization of ZO-1 and Cx43 at the ventricular intercalated disc and modestly decreased left ventricular ejection fraction, suggesting ZO-1 is differentially required for AV node and ventricular conduction., Conclusions: ZO-1 is a key protein responsible for maintaining appropriate AV node conduction through maintaining gap junction protein localization.

Human cardiac slice preparations have recently been developed as a platform for human physiology studies and therapy testing to bridge the gap between animal and clinical trials. Numerous animal and cell models have been used to examine the effects of drugs, yet these responses often differ in humans. Human cardiac slices offer an advantage for drug testing in that they are directly derived from viable human hearts. In addition to having preserved multicellular structures, cell-cell coupling, and extracellular matrix environments, human cardiac tissue slices can be used to directly test the effect of innumerable drugs on adult human cardiac physiology. What distinguishes this model from other heart preparations, such as whole hearts or wedges, is that slices can be subjected to longer-term culture. As such, cardiac slices allow for studying the acute as well as chronic effects of drugs. Furthermore, the ability to collect several hundred to a thousand slices from a single heart makes this a high-throughput model to test several drugs at varying concentrations and combinations with other drugs at the same time. Slices can be prepared from any given region of the heart. In this protocol, we describe the preparation of left ventricular slices by isolating tissue cubes from the left ventricular free wall and sectioning them into slices using a high precision vibrating microtome. These slices can then either be subjected to acute experiments to measure baseline cardiac electrophysiological function or cultured for chronic drug studies. This protocol also describes dual optical mapping of cardiac slices for simultaneous recordings of transmembrane potentials and intracellular calcium dynamics to determine the effects of the drugs being investigated.

Small animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.

The spontaneous rhythmic action potentials generated by the sinoatrial node (SAN), the primary pacemaker in the heart, dictate the regular and optimal cardiac contractions that pump blood around the body. Although the heart rate of humans is substantially slower than that of smaller experimental animals, current perspectives on the biophysical mechanisms underlying the automaticity of sinoatrial nodal pacemaker cells (SANCs) have been gleaned largely from studies of animal hearts. Using human SANCs, we demonstrated that spontaneous rhythmic local Ca 2+ releases generated by a Ca 2+ clock were coupled to electrogenic surface membrane molecules (the M clock) to trigger rhythmic action potentials, and that Ca 2+ -cAMP-protein kinase A (PKA) signaling regulated clock coupling. When these clocks became uncoupled, SANCs failed to generate spontaneous action potentials, showing a depolarized membrane potential and disorganized local Ca 2+ releases that failed to activate the M clock. β-Adrenergic receptor (β-AR) stimulation, which increases cAMP concentrations and clock coupling in other species, restored spontaneous, rhythmic action potentials in some nonbeating "arrested" human SANCs by increasing intracellular Ca 2+ concentrations and synchronizing diastolic local Ca 2+ releases. When β-AR stimulation was withdrawn, the clocks again became uncoupled, and SANCs reverted to a nonbeating arrested state. Thus, automaticity of human pacemaker cells is driven by a coupled-clock system driven by Ca 2+ -cAMP-PKA signaling. Extreme clock uncoupling led to failure of spontaneous action potential generation, which was restored by recoupling of the clocks. Clock coupling and action potential firing in some of these arrested cells can be restored by β-AR stimulation-induced augmentation of Ca 2+ -cAMP-PKA signaling., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Long QT syndrome (LQTS) is an inherited or drug induced condition associated with delayed repolarization and sudden cardiac death. The cardiac potassium channel, I Kr , and the adrenergic-sensitive cardiac potassium current, I Ks , are two primary contributors to cardiac repolarization. This study aimed to elucidate the role of β-adrenergic (β-AR) stimulation in mediating the contributions of I Kr and I Ks to repolarizing the human left ventricle (n = 18). Optical mapping was used to measure action potential durations (APDs) in the presence of the I Ks blocker JNJ-303 and the I Kr blocker E-4031. We found that JNJ-303 alone did not increase APD. However, under isoprenaline (ISO), both the application of JNJ-303 and additional E-4031 significantly increased APD. With JNJ-303, ISO decreased APD significantly more in the epicardium as compared to the endocardium, with subsequent application E-4031 increasing mid- and endocardial APD80 more significantly than in the epicardium. We found that β-AR stimulation significantly augmented the effect of I Ks blocker JNJ-303, in contrast to the reduced effect of I Kr blocker E-4031. We also observed synergistic augmentation of transmural repolarization gradient by the combination of ISO and E-4031. Our results suggest β-AR-mediated increase of transmural dispersion of repolarization, which could pose arrhythmogenic risk in LQTS patients.

In patients with penetrating neck injuries with clinical soft injury signs, and patients with hard signs of injury who do not require immediate surgery, CT angiography of the neck is the preferred imaging procedure to evaluate extent of injury. Other modalities, such as radiography and fluoroscopy, catheter-based angiography, ultrasound, and MR angiography have their place in the evaluation of the patient, depending on the specific clinical situation and question at hand. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Fenestrated endovascular aneurysm repair (FEVAR) is increasingly being used for juxtarenal aortic aneurysms. The aim of this study was to review long-term results and assess the importance of changing stent-graft design on outcomes., Methods: This was a retrospective review of all patients who underwent FEVAR within a single unit over 12 years (February 2003 to December 2015). Kaplan-Meier analysis of survival, and freedom from target vessel loss, aneurysm expansion, graft-related endoleak and secondary intervention was performed. Comparison between outcomes of less complex grafts (fewer than 3 fenestrations) and more complex grafts (3 or 4 fenestrations) was undertaken., Results: Some 173 patients underwent FEVAR; median age was 76 (i.q.r. 70-79) years and 90·2 per cent were men. Median aneurysm diameter was 63 (59-71) mm and median follow-up was 34 (16-50) months. The adjusted primary technical operative success rate was 95·4 per cent. The in-hospital mortality rate was 5·2 per cent; there was no known aneurysm-related death during follow-up. Median survival was 7·1 (95 per cent c.i. 5·2 to 8·1) years and overall survival was 60·1 per cent (104 of 173). There was a trend towards an increasing number of fenestrations in the graft design over time. In-hospital mortality appeared higher when more complex stent-grafts were used (8 versus 2 per cent for stent-grafts with 3-4 versus fewer than 3 fenestrations; P = 0·059). Graft-related endoleaks were more common following deployment of stent-grafts with three or four fenestrations (12 of 90 versus 6 of 83; P < 0·001)., Conclusion: Fenestrated endovascular aneurysm repair for juxtarenal aneurysm is associated with few aneurysm-related deaths in the long term. Significant numbers of secondary interventions are required, but the majority of these can be performed using an endovascular approach., (© 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

High reliability as a corporate value in healthcare can be achieved by meeting the "Quadruple Aim" of improving population health, reducing per capita costs, enhancing the patient experience, and improving provider wellness. This drive starts with the board of trustees, CEO, and other senior leaders who ingrain high reliability throughout the organization. At WellStar Health System, the board developed an ambitious goal to become a top-decile health system in safety and quality metrics. To achieve this goal, WellStar has embarked on a journey toward high reliability and has committed to Lean management practices consistent with the Institute for Healthcare Improvement's definition of a high-reliability organization (HRO): one that is committed to the prevention of failure, early identification and mitigation of failure, and redesign of processes based on identifiable failures. In the end, a successful HRO can provide safe, effective, patient- and family-centered, timely, efficient, and equitable care through a convergence of people, processes, and technology.

Heart failure (HF) is a major cause of morbidity and mortality worldwide. The global burden of HF continues to rise, with prevalence rates estimated at 1-2% and incidence approaching 5-10 per 1000 persons annually. The complex pathophysiology of HF impacts virtually all aspects of normal cardiac function - from structure and mechanics to metabolism and electrophysiology - leading to impaired mechanical contraction and sudden cardiac death. Pharmacotherapy and device therapy are the primary methods of treating HF, but neither is able to stop or reverse disease progression. Thus, there is an acute need to translate basic research into improved HF therapy. Animal model investigations are a critical component of HF research. However, the translation from cellular and animal models to the bedside is hampered by significant differences between species and among physiological scales. Our studies over the last 8 years show that hypotheses generated in animal models need to be validated in human in vitro models. Importantly, however, human heart investigations can establish translational platforms for safety and efficacy studies before embarking on costly and risky clinical trials. This review summarizes recent developments in human HF investigations of electrophysiology remodelling, metabolic remodelling, and β-adrenergic remodelling and discusses promising new technologies for HF research., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Cardiovascular research has made a major contribution to an unprecedented 10 year increase in life expectancy during the last 50 years: most of this increase due to a decline in mortality from heart disease and stroke. The majority of the basic cardiovascular science discoveries, which have led to this impressive extension of human life, came from investigations conducted in various small and large animal models, ranging from mouse to pig. The small animal models are currently popular because they are amenable to genetic engineering and are relatively inexpensive. The large animal models are favored at the translational stage of the investigation, as they are anatomically and physiologically more proximal to humans, and can be implanted with various devices; however, they are expensive and less amenable to genetic manipulations. With the advent of CRISPR genetic engineering technology and the advances in implantable bioelectronics, the large animal models will continue to advance. The rabbit model is particularly poised to become one of the most popular among the animal models that recapitulate human heart diseases. Here we review an array of the rabbit models of atrial and ventricular arrhythmias, as well as a range of the imaging and device technologies enabling these investigations., (Copyright © 2016. Published by Elsevier Ltd.)

The presence of a nonrecurrent inferior laryngeal nerve (NRILN) is a significant risk factor for nerve injury during thyroid, parathyroid, and vascular surgeries involving the paratracheal area of the head and neck. The objective of this report is to review the association between an aberrant right subclavian artery (SCA) identified on preoperative imaging and an NRILN identified intraoperatively during thyroid and parathyroid surgery. We reviewed 3 selected cases in which we preoperatively identified an aberrant right SCA and determined the intraoperative position of the inferior laryngeal nerve on the right. It is important to note that 1 of these cases demonstrated that the inferior laryngeal nerve may be found in its normal anatomic position, coursing inferiorly through the tracheoesophageal groove. This anatomic finding is unexpected in a patient with a preoperatively identified aberrant right SCA. We also performed a literature review of more than 250 cases to investigate the association between an intraoperative finding of NRILN and vascular anomalies on imaging. We found 5 reported cases that involved an aberrant right SCA, predictive of NRILN, with the nerve identified in the tracheoesophageal groove.

In the United States, the health of a community falls on a continuum ranging from healthy to unhealthy and fluctuates based on several variables. Research policy and public health practice literature report substantial disparities in life expectancy, morbidity, risk factors, and quality of life, as well as persistence of these disparities among segments of the population. One such way to close this gap is to streamline medical education to better prepare our future physicians for our patients in underserved communities. Medical schools have the potential to close the gap when training future physicians by providing them with the principles of social medicine that can contribute to the reduction of health disparities. Curriculum reform and systematic formative assessment and evaluative measures can be developed to match social medicine and health disparities curricula for individual medical schools, thus assuring that future physicians are being properly prepared for residency and the workforce to decrease health inequities in the United States. We propose that curriculum reform includes an ongoing social medicine component for medical students. Continued exposure, practice, and education related to social medicine across medical school will enhance the awareness and knowledge for our students. This will result in better preparation for the zero mile stone residency set forth by the Accreditation Council of Graduate Medical Education and will eventually lead to the outcome of higher quality physicians in the United States to treat diverse populations.

Purpose: To report a systematic literature review of late rupture of abdominal aortic aneurysm (AAA) after endovascular aneurysm repair (EVAR) and the results of a pooled analysis of causes, treatment, and outcomes., Methods: Electronic information sources and bibliographic reference lists were interrogated using a combination of free text and controlled vocabulary searches; 11 articles were ultimately identified that fulfilled the inclusion criteria. The articles reported a total of 190 patients who were included in the qualitative and quantitative synthesis. Mortality within 30 days or during the admission with aneurysm rupture was a primary endpoint; major perioperative morbidity was a secondary endpoint. A meta-analysis was performed for 30-day/in-hospital mortality using the random effects model., Results: A total of 152 ruptures occurred after 16,974 EVAR procedures reported by 8 of the case series, giving an incidence of 0.9% [95% confidence interval (CI) 0.77 to 1.05]. The mean time to rupture was 37 months. Twenty-nine percent (95% CI 20 to 39) of the patients had at least one previous secondary endovascular intervention following the initial EVAR, and 37% (95% CI 30 to 45) were not compliant with surveillance. Type I and III endoleaks were the predominant causes of rupture. Open surgical treatment was undertaken in 61% (95% CI 53 to 68) of the patients who underwent treatment. The pooled estimate for perioperative mortality was 32% (95% CI 24 to 41). A significantly lower mortality was found with endovascular treatment than open surgical management (p=0.027)., Conclusion: Graft-related endoleaks appear to be the predominant causes of late aneurysm rupture. Quality of and compliance with post-EVAR surveillance are important factors in late rupture; a large proportion of late ruptures are amenable to endovascular treatment., (© The Author(s) 2015.)

Context: When a health care system deals with complex trauma patients while simultaneously serving as an educational platform, teamwork and clear communication are imperative. While there are numerous tools and resources available to address the concerns surrounding patient safety, Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) emphasizes a team approach to improve communication among all caregivers and is specifically designed to improve patient safety through improved communication. This article reports the interim results of implementation of TeamSTEPPS in the operating room environment at the most complex and busiest tertiary military trauma center in the Department of Defense in the midst of the longest period of continuous combat operations in US history., Methods: Data were collected from December 2013 through March 2014 on the number of total cases performed by month, number of debrief surveys submitted for those months, and associated percentage of surveys completed based on case category., Results: The overall compliance rate for the TeamSTEPPS process (from the pre-op brief to the debrief survey completion) was 75.1%. Responses showed a decrease in concerns in all areas during the period of observation. Equipment-related complaints decreased by 48%; instrument-related issues decreased by 29.9%; supply issues decreased by 53.3%; personnel issues decreased by 90.5%; case scheduling issues decreased by 35.7%; and preference card issues decreased by 72.1%., Conclusions: Our results demonstrate that TeamSTEPPS can be successfully implemented in an integrated level-1 trauma center in the midst of combat casualty care with a greater than 75% overall compliance with TeamSTEPPS briefs. Further study on the sustainability of these results and the effect on operating room safety, productivity, and efficiency is necessary.

Objective: This study analyzed outcomes for patients with persistent intraoperative type Ia endoleaks after standard endovascular aneurysm repair (EVAR)., Methods: The study group was identified from a consecutive cohort of 209 patients undergoing EVAR in a tertiary center in the United Kingdom during a 2-year period. Data prospectively collected on departmental computerized databases were retrospectively analyzed. Primary outcome parameters were defined as freedom from type Ia endoleak, EVAR-related reintervention, aneurysm rupture, and aneurysm-related mortality., Results: A completion angiogram identified 44 patients (21%) as having a type Ia endoleak, and 33 (75%) had a persistent endoleak after intraoperative adjunctive procedures, including repeated balloon moulding, aortic cuff extension, and Palmaz stent (Cordis, Miami Lakes, Fla) deployment. In the 11 patients (25%) whose endoleak was successfully abolished intraoperatively, there was no recurrence of type Ia endoleak or secondary intervention to treat type 1a endoleak during a median follow-up period of 27 months. Of the 33 patients with persistent endoleak, 31 (94%) demonstrated resolution of the endoleak on first surveillance computed tomography angiography. One patient was lost to follow-up. Embolization of the endoleak in another patient was successful using Onyx (Micro Therapeutics, Inc, Irvine, Calif) 8 days after the initial procedure. No type Ia endoleak was identified after this on any surveillance imaging, and the patient was alive 28 months later with a stable aneurysm size. In the rest of the patients, no recurrence of the endoleak in any subsequent imaging was noticed, and no secondary intervention was required during follow-up. No aneurysm-related deaths occurred, and 91% of the patients had a stable or shrinking aneurysm., Conclusions: Despite adjunctive intraoperative maneuvers, persistent type Ia endoleaks can be relatively common. Our study indicates that they may be observed in selected patients. Further research is required to investigate the natural course and management of type Ia endoleaks identified intraoperatively., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Compelling evidence from large randomized trials demonstrates the salutary effects of statins on primary and secondary protection from adverse cardiovascular events in high-risk populations. Our objective was to investigate the role of perioperative statin therapy in noncardiac vascular and endovascular surgery., Methods: Electronic information sources were systematically searched to identify studies comparing outcomes after noncardiac surgical or endovascular arterial reconstruction in patients who were and were not taking statin in the perioperative or peri-interventional period. The Cochrane Collaboration's tool and the Newcastle-Ottawa scale were used to assess the methodologic quality and risk of bias of the selected studies. Random-effects models were applied to calculate pooled outcome data., Results: Four randomized controlled trials and 20 observational cohort or case-control studies were selected for analysis. The randomized studies enrolled 675 patients, and the observational studies enrolled 22,861 patients. Statin therapy was associated with a significantly lower risk of all-cause mortality (odds ratio [OR], 0.54; 95% CI, [CI], 0.38-0.78), myocardial infarction (OR, 0.62; 95% CI, 0.45-0.87), stroke (OR, 0.51; 95% CI, 0.39-0.67), and the composite of myocardial infarction, stroke, and death (OR, 0.45; 95% CI, 0.29-0.70). No significant differences in cardiovascular mortality (OR, 0.82; 95% CI, 0.41-1.63) and the incidence of kidney injury (OR, 0.90; 95% CI, 0.58-1.39) between the groups were identified., Conclusions: Our analysis demonstrated that statin therapy is beneficial in improving operative and interventional outcomes and should be considered as part of the optimization strategy for prevention of adverse cardiovascular and cerebrovascular events and death., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Secure fixation of endovascular stent grafts is essential for successful endovascular aneurysm repair. Hemodynamic distraction forces are generated by blood pressure and blood flow and act against fixation force to encourage migration that may eventually lead to late stent graft failure. The aim of this in silico study was to determine which morphologic features were associated with greater distraction force., Methods: Computer models of 54 in situ fenestrated stent grafts were constructed from postoperative computed tomography scans by use of image processing software. Computational fluid dynamic analysis was then performed by use of a commercial finite volume solver with boundary conditions representative of peak systole. Distraction force results were obtained for each component of the stent graft. Distraction force was correlated with lumen cross-sectional area (XSA) at the inlet and outlet of components and was compared between groups of components, depending on the magnitude of four predefined angles within the aortoiliac territory that we describe in detail., Results: Median total resultant distraction force (RDF) acting on the fenestrated proximal bodies was 4.8 N (1.3-15.7 N); bifurcated distal bodies, 5.6N (1.0-8.0 N); and limb extensions, 1.7 N (0.6-8.4N). Inlet XSA exhibited strong, positive correlation with total RDF in proximal body and distal body components (Spearman correlation coefficient ρ, 0.883 and 0.802, respectively). Outlet XSA exhibited a similarly strong, positive correlation with total RDF in limb extension components (ρ, 0.822). Outlet angulation ≥ 45 degrees was associated with greater total RDF in the limb extension components only (P = .004)., Conclusions: For a given blood pressure, XSA was the most important morphologic determinant of total RDF. Angulation within the aorta was not large enough to influence this, whereas iliac angulation affecting outlet angulation of limb extension components was associated with significantly greater total RDF., (Copyright © 2014 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Meta-analysis supports patch angioplasty after carotid endarterectomy (CEA); however, studies indicate considerable variation in practice. The hemodynamic effect of a patch is unclear and this study attempted to elucidate this and guide patch width selection., Methods: Four groups were selected: healthy volunteers and patients undergoing CEA with primary closure, trimmed patch (5 mm), or 8-mm patch angioplasty. Computer-generated three-dimensional models of carotid bifurcations were produced from transverse ultrasound images recorded at 1-mm intervals. Rapid prototyping generated models for flow visualization studies. Computational fluid dynamic studies were performed for each model and validated by flow visualization. Mean wall shear stress (WSS) and oscillatory shear index (OSI) maps were created for each model using pulsatile inflow at 300 mL/min. WSS of <0.4 Pa and OSI >0.3 were considered pathological, predisposing to accretion of intimal hyperplasia. The resultant WSS and OSI maps were compared., Results: The four groups comprised 8 normal carotid arteries, 6 primary closures, 6 trimmed patches, and seven 8-mm patches. Flow visualization identified flow separation and recirculation at the bifurcation increased with a patch and was related to the patch width. Computational fluid dynamic identified that primary closure had the fewest areas of low WSS or elevated OSI but did have mild common carotid artery stenoses at the proximal arteriotomy that caused turbulence. Trimmed patches had more regions of abnormal WSS and OSI at the bifurcation, but 8-mm patches had the largest areas of deleteriously low WSS and high OSI. Qualitative comparison among the four groups confirmed that incorporation of a patch increased areas of low WSS and high OSI at the bifurcation and that this was related to patch width., Conclusions: Closure technique after CEA influences the hemodynamic profile. Patching does not appear to generate favorable flow dynamics. However, a trimmed 5-mm patch may offer hemodynamic benefits over an 8-mm patch and may be the preferred option., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Aphis gossypii (Glover) has been found to possess multiple mutations in the acetylcholinesterase (AChE) gene (Ace) that might involve target site insensitivity. In vitro functional expression of AChEs reveals that the resistant Ace1 (Ace1R) and Ace2 (Ace2R) were significantly less inhibited by eserine, omethoate, and malaoxon than the susceptible Ace1 (Ace1S) and Ace2 (Ace2S). Furthermore, in both the mutant and susceptible AChEs, Ace2 was significantly less sensitive to eserine, omethoate, and malaoxon than Ace1. These results suggested that both the mutant Ace1 and Ace2 were responsible for omethoate resistance, while the mutant Ace2 played a major role in insecticide resistance. The DNA copy number and transcription level of Ace2 were 1.52- and 1.88-fold higher in the ORR strain than in the OSS strain. Furthermore, the DNA copy number and transcription level of Ace2 were significantly higher than that of Ace1 in either OSS or ORR strains, demonstrating the involvement of Ace2 gene duplication in resistance. Thus, the authors conclude that omethoate resistance in cotton aphids appears to have evolved through a combination of multiple mutations and extensive Ace2R gene duplication., (Copyright © 2012 Wiley Periodicals, Inc.)

Existing literature indicates significant comorbidity between posttraumatic stress disorder (PTSD) and major depression. We examined whether PTSD's dysphoria and mood/cognitions factors, conceptualized by the empirically supported four-factor DSM-5 PTSD models, account for PTSD's inherent relationship with depression. We hypothesized that depression's somatic and non-somatic factors would be more related to PTSD's dysphoria and mood/cognitions factors than other PTSD model factors. Further, we hypothesized that PTSD's arousal would significantly mediate relations between PTSD's dysphoria and somatic/non-somatic depression. Using 181 trauma-exposed primary care patients, confirmatory factor analyses (CFA) indicated a well-fitting DSM-5 PTSD dysphoria model, DSM-5 numbing model and two-factor depression model. Both somatic and non-somatic depression factors were more related to PTSD's dysphoria and mood/cognitions factors than to re-experiencing and avoidance factors; non-somatic depression was more related to PTSD's dysphoria than PTSD's arousal factor. PTSD's arousal did not mediate the relationship between PTSD's dysphoria and somatic/non-somatic depression. Implications are discussed., (© 2013 Published by Elsevier Ireland Ltd.)

Objective: This article reports the incidence, timing, and related sequelae for proximal and distal migration of the Zenith Fenestrated AAA Endovascular Graft (Cook Medical, Bloomington, Ind) used to treat abdominal aortic aneurysms., Method: A prospectively maintained database at a tertiary referral hospital was used to identify 83 patients who underwent endovascular repair using the Zenith fenestrated stent graft. Inclusion criteria included a postoperative computed tomography (CT) scan within 6 weeks of implantation and at least one additional follow-up CT scan (>5 months) available electronically at our institution. Eligible patients underwent assessment of stent graft migration using a CT-based central luminal line (CLL) technique. The proximal and distal margins of the stent graft were measured using CLLs relative to vascular landmarks on all available follow-up CT scans. Migration was defined as stent graft movement ≥4 mm., Results: Fifty-five patients were included in this study, mean age was 74 ± 7 years, and 89% were men. Mean preoperative aneurysm diameter was 67 ± 9 mm. In these 55 patients, fenestrations were applied to 162 target vessels with the commonest design accommodating two renal arteries (RAs) and the superior mesenteric artery (SMA). Median follow-up was 24 (range, 5-97) months; 80% of patients (n = 44) had both the proximal and two distal attachment sites assessed for evidence of migration. Twelve iliac limbs in 11 patients were excluded from analysis due to occlusion of one internal iliac artery precluding CLL assessment (n = 7), or image quality issues (n = 5). Using CLLs and based on those patients who exhibited migration, the median proximal and distal migration distances were +5.0 (range, +4.0 to +8.1) mm and -5.0 (range, -4.3 to -21.3) mm, respectively. Kaplan-Meier analysis for proximal migration revealed migration rates of 14% and 22% at 12 and 36 months, respectively. Distal migration rates were lower at 3% and 8%, respectively. There have been no incidences of late rupture or open conversion. Of the patients with proximal migration, two patients lost a single target vessel (two RAs) and three patients were reported to have target vessel stenosis (two SMAs, one RA). These cases did not require reintervention., Conclusions: Both suprarenal fabric extension and visceral artery stenting are known to provide additional fixation for fenestrated aortic stent grafts. Despite this, minor proximal migration still occurs in up to one quarter of fenestrated endovascular repair patients by 4 years. We believe this is mainly due to the engagement of the barbs of the anchoring stent. Distal migrations occur with lower frequency., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: To report an initial experience of concomitant endovascular repair of abdominal aortic aneurysms (AAA) and cardiac surgery., Methods: Records for 10 consecutive patients (all men; median age 68 years, range 60-79) with AAA treated by a multidisciplinary team at a tertiary specialist center were retrospectively reviewed. Each patient had independent indications for surgical correction of their cardiac disease and AAAs. The patients underwent endovascular aneurysm repair (EVAR) followed by cardiac surgery under the same anesthesia. Eight patients had concomitant coronary artery bypass grafting (CABG; 4 off-pump), 1 patient had CABG and left ventricular aneurysmectomy, and 1 patient required aortic root replacement., Results: All combined procedures were performed successfully under a single general anesthesia and took a median of 508 minutes (range 425-625). Median intensive care stay was 3 days (range 2-4), while hospital stay was 8 days (range 7-21) days. There were no deaths in-hospital or within 30 days. Complications were minor and self-limiting; there were no instances of renal failure. At a median follow-up of 29 months (range 14-38), no EVAR-related secondary interventions were required., Conclusion: Concomitant EVAR and cardiac surgery delivered by a multidisciplinary team is feasible, appears safe, and eliminates the risk associated with staged operations. Improved patient satisfaction and efficient use of resources are potential advantages.

Stent fracture after fenestrated endovascular aneurysm repair is a recognized complication. In this report, we record the occurrence of superior mesenteric artery stent fractures in our series and describe the management of embolized stent fragments during secondary intervention., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: Balloon expandable stents may on occasion be deployed in close proximity to the anchoring barbs of endovascular grafts. The aim of this study was to determine the risk and effect of balloon perforation by anchoring barbs and to assess whether these risks are different if the balloon is protected by a covered stent mounted upon it., Methods: A bench-top model was developed to mimic the penetration of anchoring barbs into the lumen of medium sized blood vessels. The model allowed variation of angle and depth of vessel penetration. Both bare balloons and those with covered stents mounted upon them were tested in the model to determine whether there was a risk of perforation and which factors increased or decreased this risk., Results: All combinations of barb angle and depth caused balloon perforation but this was most marked when the barb was placed perpendicular to the long axis of the balloon. When the deployment of covered stents was attempted balloon perforation occurred in some cases but full stent deployment was achieved in all cases where the perforation was in the portion of the balloon covered by the stent. The only situation in which stent deployment failed was where the barb was intentionally placed in the uncovered portion of the balloon. This resulted in only partial deployment of the stent., Conclusions: Balloon rupture is a distinct possibility when deploying balloon-expandable stents in close proximity to anchoring barbs. Care should be taken in this circumstance to ensure that the barb is well away from the uncovered portion of the balloon., (Copyright © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Rationale: α7 nicotinic acetylcholine receptor (nAChR) agonists are proposed as candidate agents for the adjunctive treatment of cognitive deficits associated with schizophrenia. Despite the pursuit of such an approach clinically, it is surprising that the preclinical profile of pro-cognitive agents in conjunction with antipsychotic drugs is currently unexplored., Objectives: We determined if the memory-enhancing effects of the selective α7 nAChR agonist WYE-103914 were preserved in the presence of the atypical antipsychotic drug risperidone, and if the antipsychotic-like profile of risperidone was preserved in the presence of WYE-103914., Methods: Using the rat novel object recognition (NOR) paradigm, the maintenance of memory-enhancing activity of the α7 nAChR agonist WYE-103914 in the presence of risperidone was examined. Similarly, in the standard tests of antipsychotic-like activity, apomorphine-induced climbing (AIC) in mice and conditioned avoidance responding (CAR) in rats, the preservation of antipsychotic-like activity of risperidone was evaluated in the presence of WYE-103914., Results: WYE-103914 exhibited memory-enhancing activity in rat NOR, and this effect of WYE-103914 was retained in the presence of risperidone. In AIC, the atypical antipsychotic profile of risperidone was not significantly altered by WYE-103914. In contrast, WYE-103914 moderately potentiated the efficacy profile of risperidone in CAR, an effect that did not appear to be convincingly linked to a pharmacokinetic interaction., Conclusions: These data underscore the value of a preclinical evaluation of the adjunctive profile of a memory-enhancing agent in combination with antipsychotics and provide further support to augmentation with α7 nAChR agonists to address the cognitive deficits associated with schizophrenia.

Purpose: To measure the stiffness of commonly used "stiff" guidewires in terms of their flexural modulus, an engineering parameter related to bending stiffness., Methods: Eleven different intact stiff guidewires were selected to undergo a 3-point bending test performed using a tensile testing machine. Testing was performed on 3 new and intact specimens of each guidewire at 10 locations along the wire's length, excluding the floppy tip. The flexural modulus (in gigapascals, GPa) was calculated from the results of the bending test., Results: The flexural modulus of the plain Amplatz wire was 9.5 GPa compared to 11.4 to 14.5 GPa for the "heavy duty" wires. Within the Amplatz family of guidewires, the flexural modulus was 17 GPa for the "stiff," 29.2 GPa for the "extra stiff," 60.3 GPa for the "super stiff," and 65.4 GPa for the "ultra stiff." The Backup Meier measured 139.6 GPa and the Lunderquist Extra Stiff 158.4 GPa., Conclusion: The Instructions for Use of some endovascular devices specify a wire type selected from a range of undefined "stiffness" descriptors. These descriptors have little correlation with the measured flexural modulus. Two guidewires with the description "extra stiff" can have a 5-fold difference in flexural modulus. We recommend that guidewire catalogues and packaging include the flexural modulus and that device manufacturers amend their Instructions for Use accordingly.

Purpose: To quantify the compression force acting on target vessel stents as a consequence of the misalignment between the native aortic anatomy and the fenestrated stent-graft owing to measuring errors during the design of the device., Methods: The material properties of a fenestrated Zenith stent-graft were determined using a standardized tensile testing protocol. Aortic anatomy was modeled using fresh porcine aortas that were subjected to tensile testing. The net force acting on a target vessel stent due to incremental discrepancy between the target vessel ostia and the stent-graft fenestrations was calculated as the difference in wall tension between the aorta and the stent-graft in diastole and systole. The change in diameter between diastole and systole was set to 8%., Results: Using the diastole model, underestimation of circumferential target vessel position by 15°, 22.5°, and 30° resulted in net forces on the target vessel stent of 0.6, 0.8, and 1.1 N, respectively. Overestimation of target vessel position by the same increments resulted in net forces of 0.3, 0.6, and 0.9 N, respectively. With the systolic model, underestimating target vessel position by 30° resulted in a 2.1-N maximum force on the stent, which potentially threatened the seal. In the longitudinal direction, underestimating target vessel separation by up to 10 mm resulted in a maximal force on the stent of 6.1 N, while overestimating target vessel separation did not result in any additional force on the stent due to fabric infolding., Conclusion: The magnitude of the forces generated solely due to mismatch between stent-graft design and native anatomy is modest and is unlikely to cause significant deformation of target vessel stents. Mismatch, however, may cause loss of seal.