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Recent evidence demonstrated that alterations in the QT interval duration on the ECG are not only determined by mutations in genes for ion channels, but also by modulators of ion channels. Changes in the QT interval duration beyond certain thresholds are pathological and can lead to sudden cardiac death. We here focus on the ion channel modulator nitric oxide synthase 1 adaptor protein (Nos1ap). Whole‐cell patch‐clamp measurements of a conditional transgenic mouse model exhibiting cardiac‐specific Nos1ap over‐expression revealed a Nos1ap‐dependent increase of L‐type calcium channel nitrosylation, which led to increased susceptibility to ventricular tachycardias associated with a decrease in QT duration and shortening of APD90 duration. Survival was significantly reduced (60% after 12 weeks vs. 100% in controls). Examination of the structural features of the hearts of transgenic mice revealed constant heart dimensions and wall thickness without abnormal fibrosis content or BNP production after 3 months of Nos1ap over‐expression compared to controls. Nos1ap over‐expression did not alter cGMP production or ROS concentration. Our study showed that myocardial over‐expression of Nos1ap leads to the shortening of the QT interval and reduces the survival rate of transgenic animals, perhaps via the development of ventricular arrhythmias. We conclude that Nos1ap overexpression causes targeted subcellular localization of Nos1 to the CaV1.2 with a subsequent decrease of ADP90 and the QT interval. This causes detrimental cardiac arrhythmias in transgenic mice. [ABSTRACT FROM AUTHOR]

Background and Aim. In cardiorenal syndrome (CRS) type 3, acute kidney injury (AKI) induces and, sometimes, even perpetuates acute cardiac pathologies such as arrhythmias with or without cardiac decompensation or the latter due to other causes. Epidemiological data on CRS type 3 are limited. The aim of this study was to analyze epidemiological and outcome variables in CRS type 3. Methods. A single-center, retrospective and observational trial. All subjects with positive AKI alert, treated at the University Hospital Brandenburg between January and December 2019, were evaluated. Definition of CRS type 3 was according to predefined criteria. The three endpoint categories were in-hospital death, dialysis, and recovery of kidney function. Results. A total number of 1,334 AKI alerts were screened. Finally, 95 subjects received the diagnosis CRS type 3. The survival rates were 47.1% (females) and 43.6% (males). 46.8% of affected females and 33.3% of the males required dialysis therapy. Complete recovery at the time of discharge occurred in 35.8%, and no recovery at all was found in 54.7%. Conclusions. All three predefined study endpoints, the mortality, the prevalence of dialysis, and the percentage of subjects without recovery of kidney function, were notably high. Therefore, AKI patients with imminent or established cardiac complications require the highest attention of nephrologists in charge. [ABSTRACT FROM AUTHOR]

Aim: Arteriogenesis constitutes the most efficient endogenous rescue mechanism in cases of cerebral ischaemia. The aim of this work was to investigate whether angiotensin‐converting enzyme inhibitors (ACEi) stimulates, and angiotensin II receptor type 1 blockers (ARB) inhibits cerebral collateral growth by applying a three‐vessel occlusion (3‐VO) model in rat. Methods: Cerebral collateral growth was measured post 3‐VO (1) by assessing blood flow using the cerebrovascular reserve capacity (CVRC) technique, and (2) by assessing vessel diameters in the posterior cerebral artery (PCA) via the evaluation of latex angiographies. A stimulatory effect on arteriogenesis was investigated for ACEi administration ± bradykinin receptor 1 (B1R) and 2 (B2R) blockers, and an inhibitory effect was analysed for ARB administration. Results were validated by immunohistochemical analysis and mechanistic data were collected by human umbilical vein endothelial cell (HUVEC) viability or scratch assay and monocyte (THP‐1) migration assay. Results: An inhibitory effect of ARB on arteriogenesis could not be demonstrated. However, collateral growth measurements demonstrated a significantly increased CVRC and PCA diameters in the ACEi group. ACEi stimulates cell viability and migration, which could be partially reduced by additional administration of bradykinin receptor 1 inhibitor (B1Ri). ACEi inhibits the degradation of pro‐arteriogenic bradykinin derivatives, but combined ACEi + B1Ri + B1Ri (BRB) treatment did not reverse the stimulatory effect. Yet, co‐administration of ACEi + BRB enhances arteriogenesis and cell migration. Conclusion: We demonstrate a potent stimulatory effect of ACEi on cerebral arteriogenesis in rats, presumable via B1R. However, results imply a pleiotropic and compensatory effect of ACEi on bradykinin receptor‐stimulated arteriogenesis. [ABSTRACT FROM AUTHOR]

This work explored the mechanism of augmented stress‐induced vascular reactivity of senescent murine femoral arteries (FAs). Mechanical and pharmacological reactivity of young (12–25 weeks, y‐FA) and senescent (>104 weeks, s‐FAs) femoral arteries was measured by wire myography. Expression and protein phosphorylation of selected regulatory proteins were studied by western blotting. Expression ratio of the Exon24 in/out splice isoforms of the regulatory subunit of myosin phosphatase, MYPT1 (MYPT1‐Exon24 in/out), was determined by polymerase chain reaction (PCR). While the resting length–tension relationship showed no alteration, the stretch‐induced‐tone increased to 8.3 ± 0.9 mN in s‐FA versus only 4.6 ± 0.3 mN in y‐FAs. Under basal conditions, phosphorylation of the regulatory light chain of myosin at S19 was 19.2 ± 5.8% in y‐FA versus 49.2 ± 12.6% in s‐FA. Inhibition of endogenous NO release raised tone additionally to 10.4 ± 1.2 mN in s‐FA, whereas this treatment had a negligible effect in y‐FAs (4.8 ± 0.3 mN). In s‐FAs, reactivity to NO donor was augmented (pD2 = −4.5 ± 0.3 in y‐FA vs. ‐5.2 ± 0.1 in senescent). Accordingly, in s‐FAs, MYPT1‐Exon24‐out‐mRNA, which is responsible for expression of the more sensitive to protein‐kinase G, leucine‐zipper‐positive MYPT1 isoform, was increased. The present work provides evidence that senescent murine s‐FA undergoes vascular remodelling associated with increases in stretch‐activated contractility and sensitivity to NO/cGMP/PKG system. [ABSTRACT FROM AUTHOR]

Objectives: Low emotional intelligence (EI) may predispose individuals to applying maladaptive coping strategies. This may maintain anxious worrying, which is highly prevalent in patients with chronic heart failure (CHF) and may affect mental (MCS) and physical component summaries (PCS) of health-related quality of life (HRQoL).Design: The current study is a cross-sectional and cross-cultural survey.Methods: N = 200 outpatients with CHF were recruited at cardiology institutes in Germany and Pakistan and assessed with self-report questionnaires.Results: Path analysis (χ2 (4) = 7.59, p = .11, GFI = .99) revealed that the expected associations between low EI and lower SF-36 MCS and PCS of HRQoL were fully mediated by negative metacognition and maladaptive coping in the Pakistani sample (p's ≤ .05). The German sample applied different maladaptive coping strategies, which also led to lower MCS and PCS scores, but did not mediate a direct positive effect of EI on HRQoL.Conclusion: The current findings support culture-independent validity of the metacognitive model but also reveal major cultural differences regarding the application and effect of specific maladaptive coping strategies. This has important implications for caregivers in a cross-cultural context and highlights the need for culture-specific tailoring of psychosocial interventions. Statement of contribution What is already known on this subject? Worry, an integral component of generalized anxiety disorder (GAD) and highly comorbid in chronic heart failure (CHF) patients, contributes to anxiety and resulting stress as evident from metacognitive model of GAD. In addition, previous literature has also established the protective role of emotional intelligence (EI) against stress, thus maintaining quality of life. What does this study add? Cross-cultural (Pakistan vs. Germany) validation of the metacognitive model of GAD. Supportive evidence for the metacognitive model in patients with CHF. Mediation of maladaptive metacognitions and negative coping in the relationship of low trait EI and low health-related quality of life. [ABSTRACT FROM AUTHOR]

Electromagnetic geophysical methods often rely on measurements of naturally occurring or artificially impressed electric fields. It is technically impossible, however, to measure the electric field directly. Instead, the electric field is approximated by recording the voltage difference between two electrodes and dividing the obtained voltage by the distance between the electrodes. Typically, modelling and inversion algorithms assume that the electric fields are obtained over infinitely short point‐dipoles and thus measured fields are assigned to a single point between the electrodes. Such procedures imply several assumptions: (1) The electric field between the two electrodes is regarded as constant or being a potential field and (2) the receiver dimensions are negligible compared to the dimensions of the underlying modelling grid. While these conditions are often fulfilled for horizontal electric fields, borehole sensors for recordings of the vertical electric field have dimensions in the order of ≈100 m and span several modelling grid cells. Observations from such elongated borehole sensors can therefore only be interpreted properly if true receiver dimensions and variations of electrical conductivity along the receiver are considered. Here, we introduce a numerical solution to include the true receiver geometry into electromagnetic modelling schemes, which does not rely on such simplifying assumptions. The algorithm is flexible, independent of the chosen numerical method to solve Maxwell's equations and can easily be implemented in other electromagnetic modelling and inversion codes. We present conceptual modelling results for land‐based controlled source electromagnetic scenarios and discuss consideration of true receiver geometries for a series of examples of horizontal and vertical electric field measurements. Comparison with Ez data measured in an observation borehole in a producing oil field shows the importance of both considering the true length of the receiver and also its orientation. We show that misalignment from the vertical axis as small as 0.1° may seriously distort the measured signal, as horizontal electric field components are mapped into the desired vertical component. Adequate inclusion of elongated receivers in modelling and inversion can also help reducing effects of static shift when interpreting (natural source) magnetotelluric data. [ABSTRACT FROM AUTHOR]

Objective: Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.Methods: To determine the long-term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30-minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.Results: Focal cerebral ischemia induced a long-term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.Interpretation: Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β-blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729-743. [ABSTRACT FROM AUTHOR]

A rare consequence of dog bites is the infection with Capnocytophaga canimorsus, and only a few cases have been documented. We describe a 41-year-old, formerly healthy woman who died from septic shock and multiorgan failure. It is the first case of a young individual without obvious immunosuppression. [ABSTRACT FROM AUTHOR]

Thrombus-in-transit crossing an interatrial communication is a rare but potentially serious clinical condition, which has so far not been described after implantation of left atrial appendage ( LAA) closure devices. Here, we describe the case of a 76-year-old woman with permanent atrial fibrillation and contraindication for oral anticoagulation therapy, who developed pericardial tamponade and acute pulmonary embolism with visible thrombus-in-transit formation following LAA closure. Most likely manipulation of the Watchman device in the LAA during two failed attempts in device positioning led to pericardial tamponade and venous puncture, manual compression after completion of the procedure and further immobilization resulted in deep vein thrombosis with consecutive pulmonary embolism and thrombus-in-transit formation. This case highlights the value of echocardiography after LAA closure. [ABSTRACT FROM AUTHOR]

ABSTRACT We carried out a magnetotelluric field campaign in the South-East Lower Saxony Basin, Germany, with the main goal of testing this method for imaging regional Posidonia black shale sediments. Two-dimensional inversion results of the magnetotelluric data show a series of conductive structures correlating with brine-saturated sediments but also with deeper, anthracitic Westphalian/Namurian coals. None of these structures can be directly related with the Posidonia black shale, which appears to be generally resistive and therefore difficult to resolve with the magnetotelluric method. This assumption is supported by measurements of electrical resistivity on a set of Posidonia shale samples from the Hils syncline in the Lower Saxony basin. These rock samples were collected in shallow boreholes and show immature (0.53% Ro), oil (0.88% Ro), and gas (1.45% Ro) window thermal maturities. None of the black shale samples showed low electrical resistivity, particularly those with oil window maturity show resistivity exceeding 104 Ωm. Moreover, we could not observe a direct correlation between maturity and electrical resistivity; the Harderode samples showed the highest resistivity, whereas the Haddessen samples showed the lowest. A similar trend has been seen for coals in different states of thermal maturation. Saturation of the samples with distilled and saline water solutions led to decreasing electrical resistivity. Moreover, a positive correlation of electrical resistivity with porosity is observed for the Wickensen and Harderode samples, which suggests that the electrical resistivity of the Posidonia black shale is mainly controlled by porosity. [ABSTRACT FROM AUTHOR]

ABSTRACT To advance and optimize secondary and tertiary oil recovery techniques, it is essential to know the areal propagation and distribution of the injected fluids in the subsurface. We investigate the applicability of controlled-source electromagnetic methods to monitor fluid movements in a German oilfield (Bockstedt, onshore Northwest Germany) as injected brines (highly saline formation water) have much lower electrical resistivity than the oil within the reservoir. The main focus of this study is on controlled-source electromagnetic simulations to test the sensitivity of various source-receiver configurations. The background model for the simulations is based on two-dimensional inversion of magnetotelluric data gathered across the oil field and calibrated with resistivity logs. Three-dimensional modelling results suggest that controlled-source electromagnetic methods are sensitive to resistivity changes at reservoir depths, but the effect is difficult to resolve with surface measurements only. Resolution increases significantly if sensors or transmitters can be placed in observation wells closer to the reservoir. In particular, observation of the vertical electric field component in shallow boreholes and/or use of source configurations consisting of combinations of vertical and horizontal dipoles are promising. Preliminary results from a borehole-to-surface controlled-source electromagnetic field survey carried out in spring 2014 are in good agreement with the modelling studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Electromagnetic methods are routinely applied to image the subsurface from shallow to regional structures. Individual electromagnetic methods differ in their sensitivities towards resistive and conductive structures and in their exploration depths. If a good balance between different electromagnetic data can be be found, joint 3D inversion of multiple electromagnetic datasets can result in significantly better resolution of subsurface structures than the individual inversions. We present a weighting algorithm to combine magnetotelluric, controlled source electromagnetic, and geoelectric data. Magnetotelluric data are generally more sensitive to regional conductive structures, whereas controlled source electromagnetic and geoelectric data are better suited to recover more shallow and resistive structures. Our new scheme is based on weighting individual components of the total data gradient after each model update. Norms of individual data residuals are used to assess how much of the total data gradient must be assigned to each method to achieve a balanced contribution of all datasets for the joint inverse model. Synthetic inversion tests demonstrate advantages of joint inversion in general and also the influence of the weighting. In our tests, the controlled source electromagnetic data gradients are larger than those of the magnetotelluric and geoelectric datasets. Consequently, direct joint inversion of controlled source electromagnetic, magnetotelluric, and geoelectric data results in models that are mostly dominated by structures required by the controlled source electromagnetic data. Applying the new adaptive weighting scheme results in an inversion model that fits the data better and resembles more the original model. We used the modular system electromagnetic as a framework to implement the new joint inversion and briefly describe the new modules for forward modelling and their interfaces to the modular system electromagnetic package. [ABSTRACT FROM AUTHOR]

PDZ (PSD-95/Disc large/Zonula occludens-1) protein interaction domains bind to cytoplasmic protein C-termini of transmembrane proteins. In order to identify new interaction partners of the voltage-gated L-type Ca2+ channel Cav1.2 and the plasma membrane Ca2+ ATPase 4b (PMCA4b), we used PDZ domain arrays probing for 124 PDZ domains. We confirmed this by GST pull-downs and immunoprecipitations. In PDZ arrays, strongest interactions with Cav1.2 and PMCA4b were found for the PDZ domains of SAP-102, MAST-205, MAGI-1, MAGI-2, MAGI-3, and ZO-1. We observed binding of the Cav1.2 C-terminus to PDZ domains of NHERF1/2, Mint-2, and CASK. PMCA4b was observed to interact with Mint-2 and its known interactions with Chapsyn-110 and CASK were confirmed. Furthermore, we validated interaction of Cav1.2 and PMCA4b with NHERF1/2, CASK,MAST-205 and MAGI-3 viaimmunoprecipitation. We also verified the interaction of Cav1.2 and nNOS and hypothesized that nNOS overexpression might reduce Ca2+ influx through Cav1.2. To address this, we measured Ca2+ currents in HEK 293 cells co-expressing Cav1.2 and nNOS and observed reduced voltage-dependent Cav1.2 activation. Taken together, we conclude that Cav1.2 and PMCA4b bind promiscuously to various PDZ domains, and that our data provides the basis for further investigation of the physiological consequences of these interactions. [ABSTRACT FROM AUTHOR]

There are serious concerns regarding safety when performing magnetic resonance imaging in patients with implanted conductive medical devices, such as cardiac pacemakers, and associated leads, as severe incidents have occurred in the past. In this study, several approaches for altering an implant's lead design were systematically developed and evaluated to enhance the safety of implanted medical devices in a magnetic resonance imaging environment. The individual impact of each design change on radiofrequency heating was then systematically investigated in functional lead prototypes at 1.5 T. Radiofrequency-induced heating could be successfully reduced by three basic changes in conventional pacemaker lead design: (1) increasing the lead tip area, (2) increasing the lead conductor resistance, and (3) increasing outer lead insulation conductivity. The findings show that radiofrequency energy pickup in magnetic resonance imaging can be reduced and, therefore, patient safety can be improved with dedicated construction changes according to a 'safe by design' strategy. Incorporation of the described alterations into implantable medical devices such as pacemaker leads can be used to help achieve favorable risk-benefit-ratios when performing magnetic resonance imaging in the respective patient group. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Terra Nova, 24, 207-212, 2012 Abstract The subsurface structure of the Cape Fold Belt (CFB) that traverses southern Africa remains largely unknown because it lacks deep-penetrating, high-resolution geophysics. This hampers studies from local-scale exploration for important resources such as water, to continental-scale modelling, such as Gondwana reconstructions. Our Magnetotelluric (MT) soundings across the CFB provide a high-resolution crustal-scale electrical conductivity image. Inversion models of these data correlate well with surface geology, and resolve deep resistive roots of the CFB's regional Palaeozoic quartzite ridges (Swartberg and Outeniqua Mountains) and thin tectonic wedges of Proterozoic rocks of higher resistivity (Kango and Kaaimans Inliers), separated by 2-3 km of Cretaceous sediments in asymmetric intermontaine basins. One of these basins, the Oudtshoorn Basin, is flanked by a listric normal fault rooted in an upper crustal detachment zone, and is underlain by a massive conductivity anomaly that is likely to be a major saline water reservoir. [ABSTRACT FROM AUTHOR]

Implanted medical devices such as cardiac pacemakers pose a potential hazard in magnetic resonance imaging. Electromagnetic fields have been shown to cause severe radio frequency-induced tissue heating in some cases. Imaging exclusion zones have been proposed as an instrument to reduce patient risk. The purpose of this study was to further assess the impact of the imaging landmark on the risk for unintended implant heating by measuring the radio frequency-induced electric fields in a body phantom under several imaging conditions at 1.5T. The results show that global radio frequency-induced coupling is highest with the torso centered along the superior-inferior direction of the transmit coil. The induced E-fields inside the body shift when changing body positioning, reducing both global and local radio frequency coupling if body and/or conductive implant are moved out from the transmit coil center along the z-direction. Adequate selection of magnetic resonance imaging landmark can significantly reduce potential hazards in patients with implanted medical devices. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Radiofrequency (RF)-related heating of cardiac pacemaker leads is a serious concern in magnetic resonance imaging (MRI). Recent investigations suggest such heating to be strongly dependent on an implant's position within the surrounding medium, but this issue is currently poorly understood. In this study, phantom measurements of the RF-induced electric currents inside a pacemaker lead were performed to investigate the impact of the device position and lead configuration on the amount of MRI-related heating at the lead tip. Seven hundred twenty device position/lead path configurations were investigated. The results show that certain configurations are associated with a highly increased risk to develop MRI-induced heating, whereas various configurations do not show any significant heating. It was possible to precisely infer implant heating on the basis of current intensity values measured inside a pacemaker lead. Device position and lead configuration relative to the surrounding medium are crucial to the amount of RF-induced heating in MRI. This indicates that a considerable number of implanted devices may incidentally not develop severe heating in MRI because of their specific configuration in the body. Small variations in configuration can, however, strongly increase the risk for such heating effects, meaning that hazardous situations might appear during MRI. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the distribution of RF-induced E-fields inside a gel-filled phantom of the human head and torso and compare the results with the RF-induced temperature rise at the tip of a straight conductive implant, specifically examining the dependence of the temperature rise on the position of the implant inside the gel. MRI experiments were performed in two different 1.5T MR systems of the same manufacturer. E-field distribution inside the liquid was assessed using a custom measurement system. The temperature rise at the implant tip was measured in various implant positions and orientations using fluoroptic thermometry. The results show that local E-field strength in the direction of the implant is a critical factor in RF-related tissue heating. The actual E-field distribution, which is dependent on phantom/body properties and the MR-system employed, must be considered when assessing the effects of RF power deposition in implant safety investigations. Magn Reson Med 60:312-319, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Myocardial scars from heart surgery are a source of tachycardia, eventually causing late morbidity and sudden death. In general, catheter ablation has been shown to be an effective therapy for various rhythm disorders, but it has been rarely described after atrioventricular valve replacement. We report on a 45-year-old man who developed atrial flutter after implantation of a tricuspid valve bioprosthesis. An electrophysiological investigation revealed typical type-I counterclockwise atrial flutter that was successfully terminated by catheter ablation. A sinus rhythm was restored and remained stable during the course of treatment; the valvular function was not diminished. It is demonstrated that safe mapping and ablation of typical atrial flutter is possible after a tricuspid valve replacement. [ABSTRACT FROM AUTHOR]