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Background Endoscopic vacuum therapy (EVT) is an effective treatment option for leakage of the upper gastrointestinal (UGI) tract. The aim of this study was to evaluate the clinical impact of quality improvements in EVT management on patients’ outcome. Methods All patients treated by EVT at our center during 2012–2021 were divided into two consecutive and equal-sized cohorts (period 1 vs. period 2). Over time several quality improvement strategies were implemented including the earlier diagnosis and EVT treatment and technical optimization of endoscopy. The primary endpoint was defined as the composite score MTL30 (mortality, transfer, length-of-stay > 30 days). Secondary endpoints included EVT efficacy, complications, in-hospital mortality, length-of-stay (LOS) and nutrition status at discharge. Results A total of 156 patients were analyzed. During the latter period the primary endpoint MTL30 decreased from 60.8 to 39.0% (P = .006). EVT efficacy increased from 80 to 91% (P = .049). Further, the need for additional procedures for leakage management decreased from 49.9 to 29.9% (P = .013) and reoperations became less frequent (38.0% vs.15.6%; P = .001). The duration of leakage therapy and LOS were shortened from 25 to 14 days (P = .003) and 38 days to 25 days (P = .006), respectively. Morbidity (as determined by the comprehensive complication index) decreased from 54.6 to 46.5 (P = .034). More patients could be discharged on oral nutrition (70.9% vs. 84.4%, P = .043). Conclusions Our experience confirms the efficacy of EVT for the successful management of UGI leakage. Our quality improvement analysis demonstrates significant changes in EVT management resulting in accelerated recovery, fewer complications and improved functional outcome.

Aquatic research is often recognized as the last real adventure with dedicated scientists sailing on famous research vessels to even remotest areas like the Arctic or Antarctica taking samples with highly sophisticated scientific equipment. Such cruises or even more, scientists in submarines or ROVs are eye-catchers and get a high level of attention in the scientific, public and political community. In contrast, there is a comparatively small group of scientists which indeed physically enter the aquatic ecosystem and do science there - the group of diving scientists. Most surprisingly, this small group of scientists is sometimes not well recognized in science. Very often, scientific divers are assumed to take up their hobby and have mainly fun under water instead of doing serious scientific work. We - the scientific diver community - are often confronted with statements like “oh, you can be outside and can dive the whole day long, I have to stand the entire day in the lab. Your work must be like holydays”. Most of these colleagues have never been out the entire day in a bulky drysuit, spending hours and hours on a small boat while the colleague is under water doing fine tuned work in the three-dimensional space having the air to survive in tanks on the back. Often these colleagues have never spend 6 or more hours outside in a steady swell or with outside temperatures below 0°C of above 30°C and 100% humidity - without a private toilet - on a 6 m long RIB-boat.In this talk, we present the well harmonized European standards for doing excellent science under water, the respective European and German national bodies for scientific diving, as well as the required and recommended occupational safety standards and procedures for a successful, safe and efficient scientific work under water. In contrast, we also stress some possible reasons why doing science under water as diving scientist is, most surprisingly, much less accepted and established in science as doing aquatic science from “outside”, e.g. from a ship floating at the surface.

Background and study aims Measurement of colorectal polyp size during endoscopy is mainly performed visually. In this work, we propose a novel polyp size measurement system (Poseidon) based on artificial intelligence (AI) using the auxiliary water jet as a measurement reference. Methods Visual estimation, biopsy forceps-based estimation, and Poseidon were compared using a CT-colonography-based silicone model with 28 polyps of defined sizes. Four experienced gastroenterologists estimated polyp sizes visually and with biopsy forceps. Furthermore, the gastroenterologists recorded images of each polyp with the water jet in proximity for the application of Poseidon. Additionally, Poseidon's measurements of 29 colorectal polyps during clinical routine were compared to visual estimates. Results Visual estimation had the largest median percentage error (PE) of 25.2% (95% confidence interval (CI95%): 19.1, 30.4), followed by biopsy forceps-based estimation with median 20% (14.4, 25.6) in the silicone model. Poseidon presented a significantly lower median PE of 7.4% (5, 9.4; p

Computer-aided polyp detection (CADe) may become a standard for polyp detection during colonoscopy. Several systems are already commercially available. We report on a video-based benchmark technique for the first preclinical assessment of such systems before comparative randomized trials are to be undertaken. Additionally, we compare a commercially available CADe system with our newly developed one.ENDOTEST consisted in the combination of two datasets. The validation dataset contained 48 video-snippets with 22,856 manually annotated images of which 53.2% contained polyps. The performance dataset contained 10 full-length screening colonoscopies with 230,898 manually annotated images of which 15.8% contained a polyp. Assessment parameters were accuracy for polyp detection and time delay to first polyp detection after polyp appearance (FDT). Two CADe systems were assessed: a commercial CADe system (GI-Genius, Medtronic), and a self-developed new system (ENDOMIND). The latter being a convolutional neuronal network trained on 194,983 manually labeled images extracted from colonoscopy videos recorded in mainly six different gastroenterologic practices.On the ENDOTEST, both CADe systems detected all polyps in at least one image. The per-frame sensitivity and specificity in full colonoscopies was 48.1% and 93.7%, respectively for GI-Genius; and 54% and 92.7%, respectively for ENDOMIND. Median FDT of ENDOMIND with 217 ms (Inter-Quartile Range(IQR)8-1533) was significantly faster than GI-Genius with 1050 ms (IQR 358-2767,Our benchmark ENDOTEST may be helpful for preclinical testing of new CADe devices. There seems to be a correlation between a shorter FDT with a higher sensitivity and a lower specificity for polyp detection.

Although Atlantic cod has been observed in Svalbard waters since the 1880s, knowledge about the presence in the Arctic shallow water zone is limited. The regular catch of juvenile Atlantic cod in Kongsfjorden since 2008 is in line with an overall northward shift of boreal fish species toward the Arctic. This is the first study showing the age class composition, growth rates, and stomach content of Atlantic cod in the shallow water zone of Kongsfjorden, Svalbard. From 2012 to 2014 a total of 721 specimens were sampled in 3 to 12 m water depth. The primary age classes were identified as 0+, 1+, and 2+ using otolith age analysis. The different cohorts of these specimens show stable growth rates during the polar day and night. By stomach content analysis, we show that these specimens primarily feed on benthic food sources. These observations support the assumption that the shallow water zone of Kongsfjorden is likely to be a nursery ground for Atlantic cod.

Endoscopic treatment of pancreatic necrosis can be challenging and time-consuming because sticky necrotic debris is sometimes difficult to remove. The over-the-scope-grasper, a new tool that has recently become available for this purpose, might also be useful for other indications. However, clinical data on the efficacy and safety of this new device are lacking.To evaluate the technical success and safety of the device in a multicenter setting.The over-the-scope-grasper was used in nine selected endoscopic centers between November 2020 and October 2021 for appropriate indications. Overall, 56 procedures were included in the study. We retrospectively evaluated procedural parameters of all endoscopic interventions using a predefined questionnaire, with special respect to technical success, indications, duration of intervention, type of sedation, and complications. In the case of pancreatic necrosectomy, the access route, stent type, number of necrosis pieces removed, and clinical handling were also recorded.A total of 56 procedures were performed, with an overall technical success rate of 98%. Most of the procedures were endoscopic pancreatic necrosectomies (33 transgastric, 4 transduodenal). In 70% of the procedures, access to the necrotic cavity was established with a lumen apposing metal stent. The technical success of pancreatic necrosectomy was 97%, with a mean of 8 pieces (range, 2-25 pieces) of necrosis removed in a mean procedure time of 59 min (range, 15-120 min). In addition, the device has been used to remove blood clots (These first multicenter data demonstrate that the over-the-scope-grasper is a promising device for endoscopic pancreatic necrosectomy, which is also appropriate for removing foreign bodies and blood clots, or cleaning insufficiency cavities prior to endoluminal vacuum therapy.

Background The efficiency of artificial intelligence as computer-aided detection (CADe) systems for colorectal polyps has been demonstrated in several randomized trials. However, CADe systems generate many distracting detections, especially during interventions such as polypectomies. Those distracting CADe detections are often induced by the introduction of snares or biopsy forceps as the systems have not been trained for such situations. In addition, there are a significant number of non-false but not relevant detections, since the polyp has already been previously detected. All these detections have the potential to disturb the examiner's work. Objectives Development and evaluation of a convolutional neuronal network that recognizes instruments in the endoscopic image, suppresses distracting CADe detections, and reliably detects endoscopic interventions. Methods A total of 580 different examination videos from 9 different centers using 4 different processor types were screened for instruments and represented the training dataset (519,856 images in total, 144,217 contained a visible instrument). The test dataset included 10 full-colonoscopy videos that were analyzed for the recognition of visible instruments and detections by a commercially available CADe system (GI Genius, Medtronic). Results The test dataset contained 153,623 images, 8.84% of those presented visible instruments (12 interventions, 19 instruments used). The convolutional neuronal network reached an overall accuracy in the detection of visible instruments of 98.59%. Sensitivity and specificity were 98.55% and 98.92%, respectively. A mean of 462.8 frames containing distracting CADe detections per colonoscopy were avoided using the convolutional neuronal network. This accounted for 95.6% of all distracting CADe detections. Conclusions Detection of endoscopic instruments in colonoscopy using artificial intelligence technology is reliable and achieves high sensitivity and specificity. Accordingly, the new convolutional neuronal network could be used to reduce distracting CADe detections during endoscopic procedures. Thus, our study demonstrates the great potential of artificial intelligence technology beyond mucosal assessment.

Recent research showed how to import laser cut 3D models encoded in the form of 2D cutting plans into a 3D editor (assembler3 [28]), which allows users to perform parametric manipulations on such models. In contrast to assembler3 , which requires users to perform this process manually, we present autoAssembler, which performs this process automatically. AutoAssembler uses a beam search algorithm to search possible ways of assembling plates. It uses joints on these plates to combine them into assembly candidates. It thereby preferably pursues candidates (1) that have no intersecting plates, (2) that fit into a small bounding box, (3) that use plates whose joints fit together well, (4) that do not add many unpaired joints, (5) that make use of constraints posed by other plates, and (6) that conform to symmetry axes of the plates. This works for models that have at least one edge joint (finger or t-joint). In our technical evaluation, we imported 66 models using autoAssembler. AutoAssembler assembled 79% of those models fully automatically; another 18% of models required on average 2.7 clicks of post-processing, for an overall success rate of 97%.

Introduction Risk stratification in upper gastrointestinal bleeding (UGIB) currently relies on clinical parameters and risk scores. HemoPill® acute (Ovesco Endoscopy, Tuebingen, Germany) is a pill-shaped, orally administered sensor capsule for real-time blood detection. The aim of this study was to evaluate the system in clinical routine. Material and methods Sixty-one consecutive patients in whom the HemoPill® had been used at 12 international hospitals between July 2019 and March 2020 were retrospectively analysed. Indications for application were the clinical suspicion of UGIB, small bowel bleeding, of rebleeding after hemostasis. Primary endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse events and change of clinical course. Results The capsule was used in 45 (73%) patients with UGIB, in 12 (20%) patients with small bowel bleeding and in four (7%) patients for exclusion of rebleeding. Technical success was 98%. 35/60 (58%) cases were capsule-positive and among these, endoscopy showed bleeding in 20/35 (57%) cases. None of the 25 capsule-negative patients rebled. Emergency endoscopy could be avoided in 18/25 (72%) cases. Serious adverse events did not occur. Conclusion HemoPill®-based blood detection is feasible and safe. Negative capsule results might 'downgrade' the need for urgent endoscopy.

We demonstrate Assembler3 a software tool that allows users to perform 3D parametric manipulations on 2D laser cutting plans. Assembler3 achieves this by semi-automatically converting 2D laser cutting plans to 3D, where users modify their models using available 3D tools (kyub), before converting them back to 2D. In our user study, this workflow allowed users to modify models 10x faster than using the traditional approach of editing 2D cutting plans directly. Assembler3 converts models to 3D in 5 steps: (1) plate detection, (2) joint detection, (3) material thickness detection, (4) joint matching based on hashed joint "signatures", and (5) interactive reconstruction. In our technical evaluation, Assembler3 was able to reconstruct 100 of 105 models. Once 3D-reconstructed, we expect users to store and share their models in 3D, which can simplify collaboration and thereby empower the laser cutting community to create models of higher complexity.

We present Assembler3 a software tool that allows users to perform 3D parametric manipulations on 2D laser cutting plans. Assembler3 achieves this by semi-automatically converting 2D laser cutting plans to 3D, where users modify their models using available 3D tools (kyub), before converting them back to 2D. In our user study, this workflow allowed users to modify models 10x faster than using the traditional approach of editing 2D cutting plans directly. Assembler3 converts models to 3D in 5 steps: (1) plate detection, (2) joint detection, (3) material thickness detection, (4) joint matching based on hashed joint "signatures", and (5) interactive reconstruction. In our technical evaluation, Assembler3 was able to reconstruct 100 of 105 models. Once 3D-reconstructed, we expect users to store and share their models in 3D, which can simplify collaboration and thereby empower the laser cutting community to create models of higher complexity.

Das Ausengelande einer Einrichtung kann gezielt genutzt werden, um vielfaltige psychomotorische Erfahrungen zu ermoglichen. Im vorliegenden Beitrag soll dazu eine ordnende Aufteilung vorgestellt werden. Es werden Gestaltungselemente im naturnahen Ausengelande nach dem kompetenztheoretischen und dem sinnverstehenden Ansatz in der Psychomotorik benannt. Hierzu werden einige konkrete Hinweise zur praktischen Umsetzung dieser Gestaltungsideen vorgestellt.

Despite the increasing incidence and prevalence of Crohn’s Disease (CD), no curative options exist and treatment remains complex. While therapy has mainly focused on medical approaches in the past, growing evidence reveals that in cases of limited inflammation, surgery can suffice as an alternative primary treatment. We retrospectively assessed the disease course and outcomes of 103 patients with terminal Ileitis who underwent primary surgery (n = 29) or received primary medical treatment followed by surgery (n = 74). Primary endpoint was the need for immunosuppressive medication after surgical treatment (ileocecal resection, ICR) during a two-years follow-up. Rates for laparoscopic ICR were enhanced in case of early surgery, but no differences were seen for postoperative complications. In case of immunosuppressive medication, patients with ICR at an early state of disease needed significantly less anti-inflammatory medication during the two-year postoperative follow-up compared to patients who were primarily treated medically. Furthermore, in a subgroup analysis for patients with localized ileocecal disease manifestation, early surgery consistently resulted in a decreased amount of medical therapy postoperatively. In conclusion primary ICR is safe and effective in patients with limited CD, and the need for immunosuppressive medication during the postoperative follow-up is low compared to patients receiving surgery at a later stage of disease.

Purpose Local treatment of small well-differentiated rectal neuroendocrine tumors (NETs) is recommended by current guidelines. However, although several endoscopic methods have been established, the highest R0 rate is achieved by transanal endoscopic microsurgery (TEM). Since a recently published study about endoscopic full thickness resection (eFTR) showed a R0 resection rate of 100%, the aim of this study was to evaluate both methods (eFTR vs. TEM). Methods We retrospectively analyzed all patients with rectal NET treated either by TEM (1999–2018) or eFTR (2016–2019) in two tertiary centers (University Hospital Wuerzburg and Ulm). We analyzed clinical, procedural, and histopathological outcomes in both groups. Results Twenty-eight patients with rectal NET received local treatment (TEM: 13; eFTR: 15). Most tumors were at stage T1a and grade G1 or G2 (in the TEM group two G3 NETs were staged T2 after neoadjuvant chemotherapy). In both groups, similar outcomes for en bloc resection rate, R0 resection rate, tumor size, or specimen size were found. No procedural adverse events were noted. Mean procedure time in the TEM group was 48.9 min and 19.2 min in the eFTR group. Conclusion eFTR is a convincing method for local treatment of small rectal NETs combining high safety and efficacy with short interventional time.

Background Endoscopic removal of foreign bodies, coagulated blood, or necrotic debris is sometimes challenging and time-consuming, partly because of inadequate endoscopic instruments. Therefore, new devices are needed to overcome the current limitations. Methods The over-the-scope grasper (OTSG) is a new grasping tool that can be attached to any standard gastroscope. It has been developed for endoscopic removal of larger particles. We present retrospective data on five patients who were treated using the device for various indications, including necrosectomy, bolus impaction, and removal of blood clots. Results In two patients, the OTSG was used through a lumen-apposing metal stent for direct endoscopic necrosectomy after severe pancreatitis. The other patients had a massive blood clot in the esophagus after endoscopic submucosal dissection, or aphagia due to large meat chunks clogging the esophagus. The OTSG was used with technical success in all of the patients and without any procedure-associated complications. Conclusion The OTSG appears to be a useful device for endoscopic removal of larger particles, blood clots, or necrotic debris. Preliminary experience shows that the device is effective and easy to use.

Measuring environmental variables over longer times in coastal marine environments is a challenge in regard to sensor maintenance and data processing of continuously produced comprehensive datasets. In the project “MOSES” (Modular Observation Solutions for Earth Systems), this procedure became even more complicated because seven large Helmholtz centers from the research field Earth and Environment (E&E) within the framework of the German Ministery of Educatiopn and Research (BMBF) work together to design and construct a large scale monitoring network across earth compartments to study the effects of short-term events on long term environmental trends. This requires the development of robust and standardized automated data acquisition and processing routines, to ensure reliable, accure and precise data.Here, the results of two intercomparison workshops on senor accuracy and precicion for selected environmental variables are presented. Environmental sensors which were to be used in MOSES campaigns on hydrological extremes (floods and draughts) in the Elbe catchment and the adjacent coastal areas in the North Sea in 2019 to 2020 were compared for selected parameters (temperature, salinity, chlorophyll-A, turbidity and methane) in the same experimentally controlled water body, assuming that all sensors provide comparable data. Results were analyzed with respect to individual sensor accuracy and precision related to an “assumed” real value as well as with respect to a cost versus accuracy/precision index for measuring specific environmental data. The results show, that accuracy and precision of sensors do not necessarily correlate with the price of the sensors and that low cost sensors may provide the same or even higher accuracy and precision values as even the highest price sensor types.

Objective To report surgical results and complications of cochlear implantation in patients with far-advanced otosclerosis (FAO). Materials and methods This was a retrospective chart review of surgical results in terms of electrode insertion as well as peri- and postoperative complications. Ten cochlear implantations (CIs) were performed in eight patients with FAO. A prior stapedotomy had been performed in all cases. Results Full electrode insertion was achieved in nine of the 10 operations (90%) and partial insertion in one operation. An unintended opening of the vestibule during drilling was the only perioperative complication. Postoperative complications occurred as two cases of vertigo (one prolonged). No chorda tympani syndrome and no cases of facial nerve stimulation were noted. Conclusion Although based on a limited number of cases, we conclude that full electrode insertion can be achieved in almost all cases and that major complications are infrequent in CI in patients with FAO. Postoperative vertigo appears to be the most commonly occurring complication.

A combined year-round assessment of selected oceanographic data and a macrobiotic community assessment was performed from October 2013 to November 2014 in the littoral zone of the Kongsfjorden polar fjord system on the western coast of Svalbard (Norway). State of the art remote controlled cabled underwater observatory technology was used for daily vertical profiles of temperature, salinity, and turbidity together with a stereo-optical assessment of the macrobiotic community, including fish. The results reveal a distinct seasonal cycle in total species abundances, with a significantly higher total abundance and species richness during the polar winter when no light is available underwater compared to the summer months when 24 h light is available. During the winter months, a temporally highly segmented community was observed with respect to species occurrence, with single species dominating the winter community for restricted times. In contrast, the summer community showed an overall lower total abundance as well as a significantly lower number of species. The study clearly demonstrates the high potential of cable connected remote controlled digital sampling devices, especially in remote areas, such as polar fjord systems, with harsh environmental conditions and limited accessibility. A smart combination of such new digital sampling methods with classic sampling procedures can provide a possibility to significantly extend the sampling time and frequency, especially in remote and difficult to access areas. This can help to provide a sufficient data density and therefore statistical power for a sound scientific analysis without increasing the invasive sampling pressure in ecologically sensitive environments.

Projections show that climate change will lead to structural change in Arctic ecosystems. Studies project the extinction of local species and intense species invasion to the Arctic Ocean. A lack of basic biological data about the Arctic shallow water fish community will make it hard to assess whether these communities will change or not. Baseline studies in combination with future reassessments are needed to establish a basic knowledge about the change of these communities. This study provides a quantitative first time description of the shallow water fish community of Kongsfjorden, Svalbard. The fish assemblage in the depth range from 3 to 12 m was determined with respect to abundance and species composition. Among a total sample size of 2804 specimens, the presence of 12 fish species and one family (Liparidae) was detected. Myoxocephalus scorpius (shorthorn sculpin) (74.9 %), Gadus morhua (Atlantic cod) (17.2 %), and Gymnocanthus tricuspis (Arctic staghorn sculpin) (3.8 %) were identified as the most abundant species across all sampling sites. A signif- icant relationship between algal coverage and fish abun- dance was detected. Furthermore, we demonstrated a fjord inward increase in biodiversity along the south shore that might be correlated with a change in hydrographic regime.

Alternative materials, like recycling materials, industrial by-products and soils already influenced by human activities (e.g. urban soils) are commonly accepted as building material in earthwork constructions. The risk of contaminant leaching from these materials can be limited by reducing the amount of percolating water. Technical safeguards are means to achieve this, but they must be adapted to the requirements of road construction. The research project aims to better knowledge of the percolation and leaching processes in road embankments constructed from alternative materials with different technical safeguards.The input and behavior of water and contaminants from re-used soils and road runoff is measured in eight field lysimeters at an urban road in an enterprise zone in Augsburg, southern Germany with about 9,700 vehicles per day. Each lysimeter contains the cut out of an embankment. The technical safeguards aim to decrease percolation and include a capillary barrier / drainage layer from geotextile and a second one from gravel, a bituminous film of 1kg/m2 and a modified mineral sealing of 10cm.A sandy gravel and a loamy soil were each used for construction of the embankment cut out in four lysimeters. The soils were spiked with a low contamination of Cd, Cu and CN- to test the efficiency of the technical safeguards. In the percolate water of the lysimeters as well as in the road runoff the pH value, electrical conductivity and the concentrations of sulphate, chloride, As, Pb, CN-, Cr, Cu, Hg, Ni, Mo, Sb, Tl, V and Zn have been analyzed in two-week composite samples since July of 2010. The amount of road runoff, lysimeter runoff and percolating water with its electrical conductivity are measured continuously. It has to be noted that measures were taken during a testing period in order to solve imperfections in the test set-up. These measures will have affected the observations presented.Results show that the unfiltered road runoff shows considerable concentrations of Zn and also elevated concentrations of Pb, as expected from former experience and literature. Up to now, all embankment types lead to a strong retention of these two substances. However, elevated Zn and Pb concentrations can be found in the percolating water during times of high chloride concentrations originating from deicing salt. Furthermore it was shown that the average contaminant leaching of each lysimeter was relatively small during the measurement period.Changes in concentrations of other parameters seem to be induced mainly by high chloride content of the infiltrating road runoff, but the time of occurrence of the changes in the effluent as well as the temporal variations depend also on the soil type, soil pH and the technical safeguards. Additionally, it seems that the soil type has a stronger influence on the percolation process compared to the different technical safeguards. Possible reasons will be discussed.

A combined year round assessment of selected oceanographic data and a macrobiotic community assessment was performed from October 2013 to November 2014 in the littoral zone of the polar fjord systems Kongsfjorden on the west coast of Svalbard (Norway). A state of the art remote controlled cabled underwater observatory technology was used for daily vertical profiles of temperature, salinity and turbidity together with a stereo-optical assessment of the macrobiotic community, including fish. The results reveal a distinct seasonal cycle in total species abundances with a significantly higher total abundance and species richness during the polar winter when no light is available under water compared to the summer months when 24-h light is available. During the winter months, a temporally highly segmented community was observed with respect to species occurrence with single species dominating the winter community for restricted times. In contrast, the summer community showed an overall lower total abundance, as well as a significantly lower number of species. The study clearly demonstrates the high potential of cable connected remote controlled digital sampling devices, especially in remote areas, such as the polar fjord systems, with harsh environmental conditions and limited accessibility. A smart combination of such new digital “sampling” methods with classic sampling procedures can provide a possibility to significantly extend the sampling time and frequency especially in remote and difficult to access areas. This can help to provide a sufficient data density and therefore statistical power for a sound scientific analysis without increasing the invasive sampling pressure in ecologically sensitive environments.

The hypothesis was tested that vardenafil, a PDE5 inhibitor, specifically enhances coronary vasodilation during acidosis. In isolated constant pressure perfused guinea pig hearts, infusion of vardenafil (or= 1 microM) increased coronary flow concentration-dependently 34 % above baseline. In parallel, cGMP release increased (0.44 +/- 0.094 vs. 0.14 +/- 0.017 pmol/min x g at 0.5 microM vardenafil vs. baseline). Flow increases occurred in the absence of changes in heart function (LVP, heart rate, dP/dt(max), heart rate - pressure product). Infusion of the NO synthase blocker L-NMMA (100 microM) caused a rightward shift of the dose-response curve of vardenafil. To test whether vardenafil treatment may enhance metabolic coronary vasodilation, arterial pCO(2) was raised from 38 to 61 mmHg, which resulted in a steady state flow increase of 18.8 +/- 4.5%. Infusion of vardenafil, given at a threshold flow enhancing concentration, doubled the coronary flow response during hypercapnic acidosis to 38.4 +/- 4.2 % (p=0.004). This flow amplification during acidosis was not shared by the K(ATP) channel opener cromakalim, indicating a specific effect of vardenafil on flow control during myocardial acidosis. We conclude that vardenafil specifically relaxes coronary resistance vessels through NO/cGMP-dependent pathways and increases the coronary flow response toward hypercapnic acidosis. This finding further supports the importance of the NO-cGMP axis in mediation of this flow response.

Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency-genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-β1- or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.

Was macht ein Extremjobber in seiner Freizeit? Er versucht, sich zu entspannen – und setzt sich dabei oft selbst unter Druck. Da er gerne 110% gibt, kann aus „einer Runde Joggen“ das Trainieren fur einen Marathon werden, aus dem einfachen „Fuse hochlegen“ ein durchgeplanter Wellness-Tag, aus dem „Abend mit Freunden“ eine Barbecue-Party mit zahlreichen Gasten. Durch zu hohe Anspruche an das Abschalten vom Job steht sich ein Extremjobber oft selbst im Weg, er will sich wenn auch „richtig“ entspannen und dabei keine halben Sachen machen.

Aims This study addressed the hypotheses that the hypercapnic flow response in wild-type (WT) mouse heart is mainly mediated by nitric oxide (NO) and, thus, severely blunted in endothelial nitric oxide synthase knockout (eNOS-KO) mice and in WT mice after continuous pharmacological block (2 weeks) of NOS enzymes (WT-LN). Methods and results Step changes of arterial pCO2 were performed in isolated perfused hearts ( n = 105). Contributions of NOS (L-NAME, TRIM), cyclooxygenase (indomethacin), epoxyeicosanotrienes (miconazole), adenosine A2A-receptors (SCH 58261), KV-channels (4-AP), KCa-channels (TEA), and KATP-channels (glibenclamide) were studied in WT and eNOS-KO mouse hearts. Change of arterial pCO2 increased coronary flow by 31.3 ± 4% in WT, a response that was significantly decreased to 9.2 ± 6% after L-NAME. Additional glibenclamide infusion ( n = 5) completely abolished the steady-state flow increase during hypercapnic acidosis (−4.2 ± 2.3%, P = 0.004 vs. control). Hearts from eNOS-KO mice as well as WT-LN showed a fully preserved flow response insensitive towards NOS-blockade. Whereas indomethacin, miconazole, TEA, and SCH 58261 were ineffective to reduce the flow response, glibenclamide blunted it in eNOS-KO hearts. Conclusion NO-production and KATP-channel activation together may fully account for the steady-state hypercapnic flow response in mouse heart. However, chronic deletion of eNOS does not result in a reduced hypercapnic flow response. Enhanced activation of KATP-channels and potentially Kv-channels contributes to the compensatory mechanisms involved in the hypercapnic flow response when eNOS activity is absent.

The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic control models have been proposed. 1) An oxygen sensor located in the wall of coronary vessels coupling to smooth muscle tension. Endothelial prostaglandin production may support this concept. 2) An oxygen sensing mechanism located in the myocardium and changing metabolism in response to changes of local pO(2). Adenosine is a metabolite produced at an accelerated rate when the supply-to-demand relationship for oxygen falls. 3) Sensing of oxygen turnover may be achieved by carbon dioxide production and, potentially, by mitochondrial production of reactive oxygen species. 4) The red blood cell might serve as an oxygen sensor in response to changes of haemoglobin oxygenation. A potential link to vessel relaxation may be red cell ATP release. A large body of experimental evidence supports the notion that K(ATP) channels play a significant role causing smooth muscle hyper-polarization. However, additional yet unknown effector mechanisms must exist, because block of K(ATP) channels does not lead to deterioration of coronary flow control under conditions of exercise. Thus, although several lines of evidence show that metabolic flow regulation is effective during hypoxic conditions,mechanisms mediating normoxic metabolic flow control still await further clarification.