Search

Background/Purpose Previous studies have shown that a patent, watertight esophageal anastomosis can be accomplished safely using specially-shaped magnets in piglets. However, it is unclear whether such a magnetic esophageal compression anastomosis (MECA) remains patent in the long-term. The purpose of this study was to evaluate the long-term outcome of MECA in an experimental pig model over an observation period of 2 months. Methods Ten piglets underwent creation of an MECA with custom-made 8 mm magnets and a U-shaped esophageal bypass loop to allow peroral nutrition at eight weeks of life. Two weeks later, the bypass loop was closed surgically, requiring the pigs to swallow via the newly created magnetic compression anastomosis. The pigs were fed soft chow for 2 months. They were monitored for weight gain and signs of dysphagia. At the endpoint of two months, esophagoscopy and contrast esophagography was performed. After removal of the esophagus, the tissues were macroscopiocally and histologically assessed. Results Six piglets survived until the endpoint. In two pigs, closure of the bypass loop failed, these demonstrated mean weight gain of 792 gs/day [95% Confidence interval 575 to 1009 gs/day]. Weight gain in four pigs that exclusively fed via the magnetic anastomosis averaged 577 gs/day [95% confidence interval 434 to 719 gs/day (p = 0.18)]. There were no signs of dysphagia. All magnets passed with the stool within 16 days. After 2 months, a well-formed magnetic compression anastomosis was visible and easily negotiated with a 6.5 mm endoscope. Esophogram and macroscopic findings confirmed patentency of the esophageal anastomoses. Histopathology showed a circular anastomosis lined with contiguous epithelium. Conclusion MECA creates a long-term functional and patent anastomosis in pigs. This concept may facilitate minimally-invasive esophageal atresia repair by obviating a technically challenging and time-consuming hand-sewn anastomosis.

Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiOEight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e.,50% in both ptiOOnly 1 of 8 animals demonstrated a decrease of50% in both ptiOIntraparenchymal multiparametric measurements of acute changes in ptiO

Background: 8-week old Sprague Dawley rats represent the standard rodent model of oesophageal surgery, which is challenging and might be eased by larger oesophageal lengths. Therefore, we aimed to ...

Introduction: Swine had special roles in the development of minimally invasive procedures to treat vesicoureteral reflux, and minipigs have been gaining ground in recent years in experimental pediatric urology as they combine small size with less vulnerable adult physiology, but their suitability as a model has never been assessed. We therefore compared a landrace piglet with a juvenile minipig to elucidate comparability. Methods: We evaluated five 3-week old Pietrain piglets and five 3-month old Aachen Minipigs as representatives of landrace and minipig models based on their expected bodyweight being similar to a newborn human. We compared renal weight, volume – via the ellipsoid formula – and ureteral length. In addition, we calculated porcine renal function via Gasthuys’ formula. In order to compare the groups with previously published values for infants, we used resampling techniques to allow comparison to humans. Results: Renal weight was higher in humans than in Pietrain piglets (ΔL = 7.6 g; ΔR = 5.4 g) and Aachen Minipigs (ΔL = 11 g; ΔR = 9.4 g). Renal volumes in humans were higher than in both Pietrain piglets (ΔL = 5.6 mL, p < 0.001; ΔR = 3.7 mL, p = 0.004) and Aachen Minipigs (ΔL = 8.1 mL; ΔR = 6.6 mL; both p < 0.001). Ureteral lengths in humans and both pig breeds were comparable as were estimated renal functions between both pig breeds. Discussion and Conclusion: Both landrace piglets and juvenile minipigs are suitable models for experimental pediatric urology as parameters did not differ between them. In addition, the anatomic parameters are comparable or smaller than in infants. This might facilitate translational research as technical failure is less likely in larger organs. Additional research is necessary to cover higher age ranges than those included in the present pilot study.

Background/aims Motility disorders are common and may affect the entire gastrointestinal (GI) tract but current treatment is limited. Multilocular sensing of GI electrical activity and variable electrical stimulation (ES) is a promising option. The aim of our study is to investigate the effects of adjustable ES on poststimulatory spike activities in 5 GI segments. Methods Six acute porcine experiments were performed with direct ES by 4 ES parameter sets (30 seconds, 25 mA, 500 microseconds or 1000 microseconds, 30 Hz or 130 Hz) applied through subserosal electrodes in the stomach, duodenum, ileum, jejunum, and colon. Multi-channel electromyography of baseline and post-stimulatory GI electrical activity were recorded for 3 minutes with hook needle and hook-wire electrodes. Spike activities were algorithmically calculated, visualized in a heat map, and tested for significance by Poisson analysis. Results Post-stimulatory spike activities were markedly increased in the stomach (7 of 24 test results), duodenum (8 of 24), jejunum (23 of 24), ileum (18 of 24), and colon (5 of 24). ES parameter analysis revealed that 80.0% of the GI parts (all but duodenum) required a pulse width of 1000 microseconds, and 60.0% (all but jejunum and colon) required 130 Hz frequency for maximum spike activity. Five reaction patterns were distinguished, with 30.0% earlier responses (type I), 42.5% later or mixed type responses (type II, III, and X), and 27.5% non-significant responses (type 0). Conclusions Multilocular ES with variable ES parameters is feasible and may significantly modulate GI electrical activity. Automated electromyography analysis revealed complex reaction patterns in the 5 examined GI segments.

Background Anastomotic tension has repeatedly been associated with anastomotic leakages after esophagectomy for cancer or esophageal atresia repair. We therefore aimed to determine which anastomotic technique would come as close as possible to the native esophagus in sustaining traction forces. Constant traction for several minutes at esophageal remnants and large suture bites are also considered relevant in long-gap esophageal atresia repair. Methods Porcine esophagi were subjected to linear traction using a motorized horizontal test stand. We compared breaking strengths of native esophagi to simple continuous, simple interrupted, stapled, and barbed suture anastomoses. We also investigated the effects of suture bite length and phases of constant traction on breaking strengths and powered all experiments to at least 80% using exploratory investigations (n = 5 per group). Results Continuous suture anastomoses had a breaking strength comparable to native esophagi (Δ = −5.25 Newton, 95% confidence interval: −10.69 to 0.19 Newton, p = 0.058) and outperformed all other investigated anastomoses (Δ ≥14.01 Newton, p ≤ 0.02). Breaking strength correlated with suture bite length (R = 0.905) and predicted breaking strength for the simple stitch (adjusted R2 = 0.812, p Conclusions Only simple continuous anastomoses achieved the linear breaking strength of native tissue. Our study provides important insights in tolerance to traction forces, but its results have to be corroborated in living animals as anastomotic leakages are multifactorial processes.

Background/purpose: Irreproducibility and missing translatability are major drawbacks in experimental animal studies. Hand-sewn anastomoses in oesophageal surgery are usually continuous, whereas th...

Purpose: This prototype catheter is a newly-developed distal access catheter featuring a self-expanding, flexible, funnel-shaped tip. The purpose of its design is to reduce the risk of thrombus fragmentation during mechanical thrombectomy and improve first-pass recanalization (TICI 3). In this experimental setup, we preclinically evaluated the effectiveness and navigability of the new catheter. Methods: A vessel model was filled with a blood-like-viscous medium, and the image was projected with the corresponding vessel area by camera transmission to correspond to the conditions in an angiography. Thrombi from porcine blood were placed into the Arteria Carotis interna of the vascular model and subsequently mechanically thrombectomized with a stent retriever. In the first part, the prototype was compared to a standard distal-access-catheter without using an external catheter. (N = 20 for each catheter). In the second part the prototype was inserted through a guiding catheter (n=11) to determine the navigability performance. Results: In the first experimental series, mechanical thrombectomy was successful 19 out of 20 times (95% success rate) for the prototype catheter versus 15 out of 20 times (75% success rate) for the standard distal-access-catheter. In the second experimental series, the prototype catheter achieved first-pass recanalization 10 out of 11 times (91 % success rate) and 1 out of 11 times at second pass (9%). Conclusion: This series of experiments demonstrated higher first-pass recanalization rates for the newly-developed funnel-shaped prototype featuring a self-expanding tip in comparison to a cylindrical standard distal-access-catheter.

Prompt reperfusion is important to rescue ischemic tissue; however, the process itself presents a key pathomechanism that contributes to a poor outcome following cardiac arrest. Experimental data have suggested the use of levosimendan to limit ischemia–reperfusion injury by improving cerebral microcirculation. However, recent studies have questioned this effect. The present study aimed to investigate the influence on hemodynamic parameters, cerebral perfusion and oxygenation following cardiac arrest by ventricular fibrillation in juvenile male pigs. Following the return of spontaneous circulation (ROSC), animals were randomly assigned to levosimendan (12 µg/kg, followed by 0.3 µg/kg/min) or vehicle treatment for 6 h. Levosimendan-treated animals showed significantly higher brain PbtO2 levels. This effect was not accompanied by changes in cardiac output, preload and afterload, arterial blood pressure, or cerebral microcirculation indicating a local effect. Cerebral oxygenation is key to minimizing damage, and thus, current concepts are aimed at improving impaired cardiac output or cerebral perfusion. In the present study, we showed that NIRS does not reliably detect low PbtO2 levels and that levosimendan increases brain oxygen content. Thus, levosimendan may present a promising therapeutic approach to rescue brain tissue at risk following cardiac arrest or ischemic events such as stroke or traumatic brain injury.

Background Mechanical thrombectomy is the standard treatment for acute ischemic stroke in patients with large vessel occlusion and can be performed up to 24h after symptom onset. Despite high recanalization rates, embolism in new territories has been reported in 8.6% of the cases. Causes for this could be clot abruption during stent retrieval into the smaller opening of a standard distal access catheter, and antegrade blood flow via collaterals despite proximal balloon protection. A funnel-shaped tip with a larger internal diameter was developed to increase the rate of first-pass recanalization and to improve the safety and efficacy of mechanical thrombectomy. Methods This in vitro study compared the efficacy of a funnel-shaped tip with a standard tip in combination with different clot compositions. Mechanical thrombectomy was performed 80 times for each tip, using two stent retrievers (Trevo XP ProVue 3/20 mm, 4/20 mm) and four different clot types (hard vs. soft clots, 0–24h vs. 72h aged clots). Results Significantly higher first-pass recanalization rates (mTICI 3) were observed for the funnel-shaped tip, 70.0% versus 30.0% for the standard tip (absolute difference, 32; relative difference 57.1%; P < .001), regardless of the clot type and stent retriever. Recanalization could be increased using harder Chandler loop clots versus softer statically generated clots, as well as 0–24h versus 72h aged clots, respectively. Conclusion The funnel-shaped tip achieved higher first-pass recanalization rates than the smaller standard tip and lower rates of clot abruption at the tip. Clot compositions and aging times impacted recanalization rates.

Implantable sensors continuously transmit information on vital values or biomarker concentrations in bodily fluids, enabling physicians to survey disease progression and monitor therapeutic success. However, currently available technologies still face difficulties with long-term operation and transferability to different analytes. We show the potential of a generalizable platform based on gold nanoparticles embedded in a hydrogel for long-term implanted biosensing. Using optical imaging and an intelligent sensor/reference-design, we assess the tissue concentration of kanamycin in anesthetized rats by interrogating our implanted sensor noninvasively through the skin. Combining a tissue-integrating matrix, robust aptamer receptors, and photostable gold nanoparticles, our technology has strong potential to extend the lifetime of implanted sensors. Because of the easy adaptability of gold nanoparticles toward different analytes, our concept will find versatile applications in personalized medicine or pharmaceutical development.

Clot-retrieval failure and embolism in new territories (ENT) are complications reducing the efficacy of mechanical thrombectomy (MT). Reasons for these problems are clot abruption during stent retriever retraction into the cylindrical tip of a standard distal access catheter (DAC), and antegrade blood flow during retrieval. To overcome these complications, a funnel-shaped tip catheter model was developed and tested. Using an experimental in vitro setup, this study compared the efficacy of a funnel-shaped tip with a standard cylindrical tip in combination with different clot compositions. Mechanical thrombectomy was performed 80 times for each tip, using two stent retrievers (Trevo XP ProVue 3/20 mm and 4/20 mm) and four different clot types (mechanical vs. static preparation, 0-24h vs. 72h clot aging times). Significantly higher first-pass recanalization rates were observed for the funnel-shaped tip, which reached 70.0% vs. 30.0% for the standard tip (absolute difference, 32; relative difference 20.0%, P

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%, Group 2: 30 ± 12%, Group 3: 18 ± 8% (p &lt, 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.

Aim of the study. To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. Clinical rationale for the study. G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. Material and methods . A controlled traumatic right sciatic nerve lesion was set using a waterjet device. Three treatment groups were created. In the first group, G-CSF was administered after sciatic nerve injury. The second group received G-CSF before and after trauma, while the third group was treated with glucose 5%-solution. Sciatic nerve function was assessed clinically and electrophysiologically at day 1, and after weeks 1, 2, 4 and 6. Additionally, α-motoneurons of the spinal cord and sciatic nerve fibres were counted at week 6. Results. Clinically, rats in both G-CSF groups improved faster compared to the control group. Additionally, animals treated with G-CSF had a significantly better improvement of motor potential amplitude and motor nerve conduction velocity at week 6 (p < 0.05). Histologically, G-CSF treatment resulted in a significantly higher number of α-motoneurons and small myelinated nerve fibres compared to placebo treatment (p < 0.05). Conclusions and clinical implications. Under G-CSF treatment, the recovery of motor nerve conduction velocity and amplitude was enhanced. Further, signs of nerve regeneration and preservation of α-motoneurons were observed. These results indicate that G-CSF might accelerate and intensify the recovery of injured nerves. Thus, treatment with G-CSF may be beneficial for patients with peripheral nerve damage, and should be explored in further clinical studies.

Delayed primary repair is still the method of choice in the management of long-gap oesophageal atresia in many centres, but the timing of anastomoses varies. Some assume the infant's bodyweight to be an important factor, whereas others prefer age. We therefore aimed to clarify whether age or bodyweight determined oesophageal length in a rodent model.We explanted the oesophagi of 20 Sprague-Dawley rats, aged 15 to 444 days (n = two per time point), measured bodyweight, oesophageal length, weight, and linear breaking strength to measure tissue resilience. Univariate and multivariate regression analyses were conducted to determine the influence of age and bodyweight on oesophageal length and linear breaking strength.All parameters were highly correlated (R 0.8), except for age and linear breaking strength (R = 0.65). Both age and bodyweight were univariate significant predictors of oesophageal length, weight, and linear breaking strength (p 0.0001). Multivariate analyses showed bodyweight to be a significant predictor of oesophageal length (p 0.0001), whereas age was not (p = 0.18) [adjusted ROnly weight determines oesophageal length and tissue resilience in rodents, whereas age is irrelevant. If a similar relationship exists in humans, it may facilitate choosing the optimum time point for delayed primary anastomosis.IV - Experimental Paper.

Introduction Long-gap esophageal atresia represents a distinct entity among the esophageal atresia spectrum. In many patients, achieving a reasonable anastomosis depends on some millimeters of tissue. We aimed to determine what effect the suturing technique would have on esophageal ex vivo elongation as it may determine the strength of a primary anastomosis. Materials and Methods In an analysis of porcine esophagi from animals for slaughter (100–120 days old with a weight of 100–120 kg), we determined esophageal length gain of simple continuous and simple interrupted suture anastomoses subjected to linear traction until linear breaking strength was reached. Statistical power of 80% was ensured based on an a priori power analysis using five specimens per group in a separate exploratory experiment. Results The simple continuous suture anastomosis in 15 porcine esophagi ( = 4.47 cm, 95% confidence interval: 4.08–4.74 cm) outperformed the simple interrupted suture anastomosis in another 15 esophagi ( = 3.03 cm, 95% confidence interval: 2.59–3.43 cm) in length gain (Δ = 1.44 cm, 95% confidence interval: 0.87–2.01 cm, p Conclusion Simple continuous anastomoses achieved higher length gain compared with simple interrupted suture anastomoses. This effect warrants an experimental assessment in vivo to assess its potential merits for clinical applicability.

Background Anastomotic tension has been linked to leakage and stenosis in esophageal surgery in both adults and children. We aimed to determine the effects of esophageal topography, operative technique, and anastomotic tension on esophageal blood flow. Materials and Methods We divided and reanastomosed the esophagi at the carinal level with increasing levels of anastomotic tension in piglets (n = 10) and sham controls (n = 4). We examined esophageal blood flow pre- and postoperatively using laser Doppler flowmetry at the anastomosis and two predetermined proximal and distal points. Blood flow in relation to distance from the anastomosis was examined by multivariate linear regression. Results Thoracotomy alone did not influence perfusion at the carinal level in shams (Δ = 3.13 laser Doppler units, 95% confidence interval: −3.4 to 9.7, p = 0.2686). We constructed a (F[5,134] = 6.34, p Conclusion Esophageal blood flow is higher at greater distances to the carinal level and hampered by esophageal division and reanastomosis. The extent of resection has less influence than previously assumed. Therefore, leakage and stenosis after esophageal anastomosis may not solely be caused by insufficient anastomotic blood flow.

The motility of the gastrointestinal tract is crucial for digestive activity and dysfunction can lead to severe disease pattern. A method for analysing the motility is needed when treatment approaches shall be evaluated. Therefore markers attached to different locations on the stomach and the bowel of pigs are video tracked in this research study. The markers are designed to provide a high contrast and have an adhesive side for fixation. Above the operation field a video camera has been placed to film the markers during the procedure. To analyse the video data a special algorithm has been implemented. The algorithm requires a registration process at the beginning of each recording which allows the parallel tracking of multiple markers. After the registration the algorithm tracks the position of the marker frame by frame. Each frame is converted into a greyscale picture by adding specified colour values of each pixel. This allows emphasizing certain colours. The centre of the marker is determined by computing the horizontal and vertical centre of the marker starting at the corresponding marker position of the previous frame. After completion the data is stored as coordinates and a video with the marker position displayed for further processing. For advanced analysis the data can be synchronized with electromyography signals, for example. The marked videos show a promising tracking of the markers. However, if the algorithm loses track of a marker during a recording, it is unlikely to relocate it due to the successive processing of the frames. Nevertheless this method provides a simple and easy to use solution for movement detection of the gastrointestinal tract.

Background A novel multiparameter brain sensor (MPBS) allows the simultaneous measurement of brain tissue oxygenation (ptiO2), cerebral blood flow (CBF), intracranial pressure (ICP), and brain temperature with a single catheter. This laboratory investigation evaluates the MPBS in an animal model in relation to established reference probes. Methods The study group consisted of 17 juvenile male pigs. Four MPBS and four reference probes were implanted per pig and compared simultaneously. The measured parameters were challenged by standardized provocations such as hyperoxia, dobutamine, and norepinephrine application, hypercapnia and hypoxia in combination with and without a controlled cortical impact (CCI) injury. Mean values over 2 min were collected for predefined time points and were analyzed using Bland–Altman plots. Results The protocol was successfully conducted in 15 pigs of which seven received CCI. ICP and ptiO2 were significantly influenced by the provocations. Subtraction of MPBS from reference values revealed a mean difference (limits of agreement) of 3.7 (− 20.5 to 27.9) mm Hg, − 2.9 (− 7.9 to 2.1) mm Hg, and 5.1 (− 134.7 to 145.0) % for ptiO2, ICP, and relative CBF, respectively. Conclusions The MPBS is a promising measurement tool for multiparameter neuromonitoring. The conducted study demonstrates the in vivo functionality of the probe. Comparison with standard probes revealed a deviation which is mostly analogous to other multiparameter devices. However, further evaluation of the device is necessary before it can reliably be used for clinical decision making. Electronic supplementary material The online version of this article (10.1007/s12028-018-0541-9) contains supplementary material, which is available to authorized users.

Background: Bipolar sealing devices are routinely used to seal blood vessels. The aim of the study is to evaluate the feasibility and safety of colonic sealing with the use of the bipolar energy devices in rats as model for experimental appendectomy. Methods: Seventy-five male Wistar rats underwent a cecal resection with four different bipolar sealing devices or a linear stapler. The harvesting procedure was performed immediately or at postoperative day (POD) 7. The sealing front bursting pressure (BP) was measured in both groups. At POD7, the resection line was clinically examined and the hydroxyproline (HDP) levels were determined. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the sealing front as well. Results: There was no mortality and no insufficiency. The BPs between the bipolar sealing devices showed no statistical differences. The early phase of the seal (POD 0) provides a low BP with an 30.8% increase until POD 7. The BPs in the stapler group showed significant better values. The hydroxyproline levels did not differ statistically between the groups. Histopathologically, there were more signs of ischemic necrosis in the stapler group than in the sealing devices groups. Conclusion: The resection and sealing of the cecum as an experimental appendectomy model with the use of bipolar energy devices proved feasible and safe in rats. The different energy devices in this study produce comparable results. To justify clinical practice in humans, several studies on the underlying mechanisms of early stage wound healing are needed.

Objective Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. Methods In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48 tenecteplase) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of tenecteplase and urokinase with different treatment periods were examined (overall 117 clots), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA or with 0.9% sodium chloride solution. Results The optimal treatment scheme of tenecteplase was found to be 100 IU with an incubation time of 30 min, for urokinase it was 50 000 IU with an incubation time of 20 min. The relative clot end weight of tenecteplase and urokinase (31.3±11.9%, 34.8 ±7.7%) was comparable to rtPA (36.7±10.7%). Larger clots were more effectively treated with tenecteplase compared to the control group (P=0.0013). urokinase and tenecteplase had similar lysis rates in aged clots and 90 min clots. One and two repetitive treatments with tenecteplase were as effective as two and three cycles of urokinase. Conclusions In our in vitro clot model we could determine optimal treatment regimens of tenecteplase (100 IU, 30 min) and urokinase (50 000 IU, 20 min). Urokinase and tenecteplase were comparable in their fibrinolytic potential compared to 1mg rtPA in small clots and showed an effective lysis in aged clots. tenecteplase was more effective in larger clots.

One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig’s blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.

Background: Prompt reperfusion is essential to rescue ischemic tissue, but in itself represents a key pathomechanism contributing to poor outcome after cardiac arrest. Experimental data suggest levosimendan as a therapeutic drug to limit ischemia-reperfusion injury by improving cerebral microcirculation and thereby reducing neuronal injury. However, recent studies question its effect on cardiac output and cerebral microcirculation in normally pumping hearts. The present study was designed to investigate the influence of levosimendan on hemodynamic parameters, cerebral perfusion, and cerebral oxygenation after cardiac arrest and resuscitation.Methods: Ventricular fibrillation was induced in anesthetized juvenile male pigs for 7 min, followed by cardiopulmonary resuscitation. After return of spontaneous circulation (ROSC) animals were randomly assigned to levosimendan (12µg/kg, followed by 0.3µg/kg/min) or vehicle (normal saline) treatment for 6 hours. Cerebral oxygen saturation and brain tissue oxygen levels were determined with near-infrared spectroscopy (NIRS) and fluorescence quenching tissue PbtO 2 probes. Cerebral and kidney perfusion were quantified by fluorescent-labeled microspheres and laser-doppler flowmetry. Results: Compared to vehicle, levosimendan treated animals showed significantly higher brain tissue oxygen levels after ROSC. This effect was not accompanied by changes in cardiac output, cardiac preload and afterload, arterial blood pressure, nor cerebral microcirculation, indicating a local levosimendan-mediated effect in the brain.Conclusions: Cerebral oxygenation is key to minimizing neurological damage during and after cardiac arrest. Therefore, current concepts aim at improving impaired cardiac output or cerebral perfusion pressure. In the present study we provide evidence that NIRS fails to reliably detect low brain tissue oxygen levels and that levosimendan improves brain oxygen content. Levosimendan may therefore present a promising therapeutic approach to rescue brain tissue at risk in patients after cardiac arrest or other causes of cerebral ischemia or malperfusion such as stroke or traumatic brain injury.

Background Fluorescent-guided techniques in vascular neurosurgery can be demonstrated via black and white indocyanine green videoangiography (ICG-VA). Multispectral imaging (MFL) is a new method, which overlaps fluorescence with the white light and provides a fluorescent white light augmented reality image to the surgeon. Objective To investigate (a) whether MFL can enhance the visualization of the blood-flow with simultaneous visualization of the anatomic structures and (b) if MFL can ergonomically improve the microvascular surgical treatment compared to ICG-VA. Methods A digital imaging of the blood flow after intravenous injection of ICG on 7 pigs was performed in real time under white light, standard fluorescence, and MFL. The blood flow was interrupted with a surgical clip, demonstrating the blockage of the blood flow. We prospectively included 30 patients with vascular deformities. The vasculature was visualized on the microscope's monitor and through the microscope's eyepiece. Results In the animal experiment, the visualization of the anatomy and the blood flow under MFL produced high resolution images. The occlusion of blood vessels demonstrated sufficiently the blockage of tissue perfusion and its reperfusion after clip removal. During all 30 surgical cases, the MFL technique and the direct delivery of the pseudo-colored image through the eyepiece allowed for enhanced anatomic and dynamic data. Conclusion MFL was shown to be superior to the classic ICG-VA, delivering enhanced data and notably improving the workflow due to the simultaneous and precise white light visualization of the blood flow and the surrounding anatomic structures.

While clinically the safety and efficacy of waterjet resection of brain tumors have been shown, evidence that waterjet dissection improves tumor resection radicality in comparison with conventional techniques is still missing. In the present study, resection radicality and tumor-free long-term survival of both techniques were evaluated in a C6-glioma model.Fifty-thousand C6-glioma cells were stereotactically transplanted in the left frontal lobe of 100 male Sprague-Dawley rats. After MRI-scanning for evaluation of tumor extension, microsurgical tumor resection was performed with conventional techniques (n=50) or with the waterjet dissector at pressures of 6bar (n=50). Twenty-five animals of each group were sacrificed after surgery for histological analysis. For analysis of survival after tumor resection, twenty-five animals of each group were followed-up to analyze tumor-free survival using the Kaplan Meier method.In the waterjet group, the resection cavity was free of C6-tumor cells in 10/25 (40%) rats showing a trend (p=0.3) towards better resection radicality compared to the rats that were treated conventionally (7/10; 28%). R1-resection with up to 250C6 cells/object slice was found in 14/25 (56%) rats after waterjet dissection compared to 6/25 (24%) rats treated conventionally showing significance (p0.01). Probability of survival was 38% after 2 weeks and 20% after 6 months in the waterjet group compared to 30% and 16% respectively in the conventional group. Diffuse tumor cell spreading with possible influence on survival was shown in 47/50 rats.In this experimental model, waterjet tumor resection did reveal significantly better resection radicality compared to the conventional technique. Although a direct transfer of these results to human glioma surgery is prohibited, the waterjet technique might contribute to the best possible resection radicality in human gliomas. Nevertheless, tumor cell spreading remains a major problem. Further studies have to address that the surgical results - in deed - improve the postoperative outcome.

Introduction: Thoracoscopic esophageal atresia repair has become increasingly popular, but is still limited to a few expert centers and has some challenges and shortcomings. One of them ha...

Introduction Fashioning a patent, watertight anastomosis in patients with esophageal atresia is a challenging task in pediatric surgery, particularly when performed under tension. A reproducible suture-less alternative would decrease operative time. We evaluated magnetic esophageal compression anastomoses in a novel bypass-loop swine model. Methods Eight-week-old piglets underwent thoracotomy to mobilize the esophagus at the carina to create a U-shaped loop. Custom-made 8 mm diameter Neodymium Magnets were inserted into the esophagus proximal and distal to the loop, then mated side-to-side at the future anastomosis site. Pigs were observed for 8 (n = 4), 10 (n = 6), and 12 (n = 2) days and then sacrificed. The magnetic compression anastomosis was evaluated macroscopically, by radiography, burst pressure testing, and histology. Results All 12 pigs survived until the endpoint. Separation of the magnets occurred at a median of 9 days. Contrast esophagrams showed patency and no leak. All anastomoses withstood pressures well over 13 kPa without leak. Histopathology showed epithelialized circular scar tissue. Conclusion Magnetic compression anastomoses of the esophagus using our specially-designed magnets are formed between the 8th and 10th postoperative day, are patent and mechanically resistant to supraphysiologic intraluminal pressures. These data lay the basis for a potential clinical application in patients born with esophageal atresia. Level of evidence Not applicable (experimental animal study).

Introduction Traction procedures are useful to preserve the child's own esophagus in long-gap forms of esophageal atresia. To date, it remains unclear what suture size or position of the traction sutures is optimal to account for differences in anatomy and to reduce the risk of traction sutures being torn out of the esophageal tissue. Materials and Methods Explanted porcine esophagi (from swine aged 100–120 days and weighing 100–120 kg) were divided at the carinal level. Traction sutures were either placed circumferentially or only in the dorsal wall and the breaking strength—circumferential disruption of the muscular layer—was measured. Suture size (USP 4–0 vs. 5–0) was also evaluated in a similar way. Results Neither traction suture position did not influence breaking strengths between circumferentially placed traction sutures or those exclusively placed in the dorsal esophageal wall (Δ = 0.47 N, 95% confidence interval: −2.83 to 3.76 N, p = 0.771, n = 11 per group) nor differing suture sizes of USP 4–0 and USP 5–0 (Δ = 1.46 N, 95% confidence interval: −3.2 to 0.28 N, p = 0.0946, n = 9 per group) affected breaking strengths. Conclusion Suture size and suture positioning do not affect mechanical stability in Foker's procedure and therefore can be adapted as needed according to patient's anatomy and size.

Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise of the mice caused the most pronounced vascular effects and dysregulation of Foxo3/circadian clock as revealed by next generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein down-regulation, and Nox2 activation. NGS revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, night-time aircraft noise increased oxidative stress, and inflammation biomarkers in serum. Conclusion Aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce night-time aircraft noise are warranted.

Intestinal electrical stimulation via implants is already used to treat several disorders like constipation or incontinence. Stimulation parameters are most often empiric and not based on systematic studies. One prerequisite to evaluate effects of intestinal electrical stimulation is a direct assessment of intestinal motility. Some common methods are strain gauge transducers or manometry. With both the methods, it is not possible to record the exact 3-D movement. Therefore, we established a new method to record gastrointestinal motility with ultraminiaturized accelerometers, directly glued to the outer surface of the stomach, small intestine, and colon. With this technique, we were able to record precise local motility changes after electrical stimulation. Due to the low energy demand and the small size of the system, it is potentially useful for chronic measurements at multiple sites of the intestinal tract. We will present our first results regarding stimulation-dependent motility changes using up to eight implanted accelerometers in an acute pig model.

Background Many centers use the Pringle's maneuver during liver resections. Since this maneuver might impair healing of bowel anastomoses, we evaluated its influence on the healing of colonic anastomosis in rats. Methods Male Wistar rats underwent median laparotomy and sigmoid resection with end-to-end anastomosis under inhalation anesthesia. Thereafter, rats received a 25 minutes Pringle's maneuver (PM, group 1) or were kept under anesthesia for the same period of time (group 2). The anastomotic bursting pressure (BP) was measured on postoperative days (POD) 3, 6 and 9. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the anastomosis. The Mann-Whitney U and χ2 -tests were used, p Results All animals (n=48) lost body weight (BW) until POD3 (95.2% vs. 85.7%, p=0.003), and BW remained lower after PM (106.2% vs. 92.8%, p=0.001). The anastomotic BP was lower in group 1 compared to group 2 on POD 3 (116mmHg vs. 176.28mmHg, p=0.001), POD 6 (182.8mmHg vs. 213mmHg, p=0.029) and POD 9 (197.2mmHg vs. 251.7mmHg, p=0.009), and mortality was higher in group 1 (1 vs. 7, p=0.022). Conclusions Pringle's maneuver increases anastomotic complications in rats. Therefore, a Pringle's maneuver should be avoided during simultaneous liver and colorectal surgery.

Until today, brain tumors especially glioblastoma are difficult to treat and therefore, results in a poor survival rate of 0-14% over five years. To overcome this problem, the development of novel therapeutics as well as optimization of neurosurgical procedures to remove the tumor tissue are subject of intensive research. The main problem of the tumor excision, as the primary clinical intervention is the diffuse infiltration of the tumor cells in unaltered brain tissue that complicates the complete removal of residual tumor cells. In this context, we are developing novel approaches for the label-free discrimination between tumor tissue and unaltered brain tissue in real-time during the surgical process. Using our impedance spectroscopy-based measurement system in combination with flexible microelectrode arrays we could successfully demonstrate the discrimination between a C6-glioma and unaltered brain tissue in an in vivo rat model. The analysis of the impedance spectra revealed specific impedance spectrum shape characteristics of physiologic neuronal tissue in the frequency range of 10-500 kHz that were significantly different from the tumor tissue. Moreover, we used an adapted equivalent circuit model to get a deeper understanding for the nature of the observed effects. The impedimetric label-free and real-time discrimination of tumor from unaltered brain tissue offers the possibility for the implementation in surgical instruments to support surgeons to decide, which tissue areas should be removed and which should be remained.

Background: The current standard for pelvic intraoperative neuromonitoring (pIONM) is based on intermittent direct nerve stimulation. This study investigated the potential use of transcutaneous sacral nerve stimulation for non‐invasive verification of pelvic autonomic nerves. Methods: A consecutive series of six pigs underwent low anterior rectal resection. For transcutaneous sacral nerve stimulation, an array of ten electrodes (cathodes) was placed over the sacral foramina (S2 to S4). Anodes were applied on the back, right and left thigh, lower abdomen, and intra‐anally. Stimulation using the novel method and current standard were performed at different phases of the experiments under electromyography of the autonomic innervated internal anal sphincter (IAS). Key Results: Transcutaneous stimulation induced increase of IAS activity could be observed in each animal under specific cathode‐anode configurations. Out of 300 tested configurations, 18 exhibited a change in the IAS activity correlated with intentional autonomic nerve damage. The damage resulted in a significant decrease of the relative area under the curve of the IAS frequency spectrum (P

arXiv:1611.05693v1.-- et al., Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants., JAG, BMB, and SD acknowledge support by the German Research Foundation (DFG) in the framework of the Priority Program 1459 Graphene, the Nanosystems Initiative Munich (NIM), and the Graphene Flagship (Contract No. 604391). JAG, BMB, SD, LR, AH and OK acknowledge support by the European Union under the NeuroCare FP7 project (Grant Agreement 280433). NTC, JW, and MVS-V acknowledge support by the EU FF7 FET CORTICONIC contract 600806. BMB, NTC, AGB, JW, SD, RV, MVS-V and JAG received funding for this project from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 696656. ICN2 acknowledges support from the Severo Ochoa Program (MINECO, Grant SEV-2013-0295).

It was tested to what extend torsional acoustic resonators can serve to in vivo differentiate between healthy and tumorous brain tissue. The resonators employed consist of crystalline quartz. They are cylindrically shaped. The resonance frequency at the fundamental is 78 kHz. The best correlation between the shifts of resonance frequency and resonance bandwidth, on the one hand, and the state of the tissue, on the other, was found when analyzing ratios of the shifts in resonance frequency and resonance bandwidth. These ratios are independent of contact area. Taking data on the fundamental mode as well as the third overtone further improved the efficiency and precision of the technique. These results suggest that torsional resonators can serve as diagnostic tools in neurosurgery.

Objective/Background Aim of the current study was to localize and differentiate between tumor (glioma) and healthy tissue in rat brains on a cellular level. Near-infrared multiphoton microscopy takes advantage of the simultaneous absorption of two or more photons to analyze various materials such as cell and tissue components via the observation of endogenous fluorophores such as NAD(P)H, FAD, porphyrins, melanin, elastin, and collagen, with a very high resolution, without inducing the problems of photo-bleaching on out-of-focus areas. Methods In vitro and in vivo studies on healthy rat brains as well as C6 glioma cell line allografts have been performed. Near-infrared laser pulses (λ = 690–1060 nm, τ ∼140 fs) generated by an ultrafast Ti:Sapphire tunable laser system (Chameleon, Coherent GmbH, Santa Clara, CA) were coupled into a laser scanning microscope (LSM 510 META, Carl Zeiss, Germany) to observe high quality images. Results Several image acquisitions have been performed by varying the zoom scale of the multiphoton microscope, image acquisition time and the wavelength (765, 840 nm) to detect various tissue components. With a penetration depth of ∼200 µm in vitro and about 30–60 µm in vivo into the brain tissue it was possible to differentiate between tumor and healthy brain tissue even through thin layers of blood. Conclusion Near-infrared multiphoton microscopy allows the observation and possibly differentiation between tumor (glioma) and healthy tissue in rat brains on a cellular level. Our findings suggest that a further miniaturization of this technology might be very useful for scientific and clinical applications in neurosurgery. Lasers Surg. Med. 44: 719–725, 2012. © 2012 Wiley Periodicals, Inc.

A recent research reveals that complement activation exacerbates cerebral infarction. However, involvement of the lectin pathway, (the third complement activation pathway) in cerebral ischemia is not well studied. In this study, we investigated the appearance of mannose-binding lectin (MBL) in ischemic brain tissue. Male Wistar rats ( n = 25) were divided into three groups: untreated control, sham, and vein occlusion (VO). Rats in the VO group had two adjacent photochemically occluded cortical veins. Regional cerebral blood flow (rCBF) was measured in the sham and VO groups. Rats were perfusion-fixed at 72 h in the sham group and at 3, 24, and 72 h after inducing ischemia in the VO group. Neuronal immunoreactivity for MBL, C1q, C3, and C5b-9 was graded on a scale from 0 (no staining) to 4 (strong immunoreactivity). rCBF significantly decreased in the VO group compared to the sham group. Immunohistochemical staining results were negative in the control group. MBL immunoreactivity was significant increased at 24 and 72 h after inducing ischemia in the VO group compared to the sham group. After inducing ischemia, C1 immunoreactivity was significantly increased at 3, 24, and 72 h, while C3 immunoreactivity increased at 72 h. C5b-9 immunoreactivity exhibited a tendency for only positive staining. In brain tissue after focal cerebral ischemia, MBL expression, as well as C1q and C3, appeared at 3 h, peaked at 24 h, and was maintained at 72 h. These results suggest that an MBL inhibitor administered during the relatively early ischemic phase might attenuate tissue damage.

Aim Intra-operative neuromonitoring is increasingly applied in several surgical disciplines and has been introduced to facilitate pelvic autonomic nerve preservation. Nevertheless, it has been considered a questionable tool for the minimization of risk, as the results are variable and might be misleading. The aim of the present experimental study was to develop an intra-operative neuromonitoring system with improved reliability for monitoring pelvic autonomic nerve function. Method Fifteen pigs underwent low anterior rectal resection with pelvic autonomic nerve preservation. Intra-operative neuromonitoring was performed under autonomic nerve stimulation with observation of electromyographic signals of the internal anal sphincter and bladder manometry. As the internal anal sphincter frequency spectrum during stimulation was found to be mainly in the range of 5–20 Hz, intra-operative neuromonitoring signals were postoperatively processed by implementation of matching band pass filters. Results In 10 preliminary experiments, signal processing was performed offline in the postoperative analysis. Of 163 stimulations intra-operatively assessed by the surgeon as positive responses, 135 (83%) were confirmed after signal processing. In the following five consecutive experiments intra-operative online signal processing was realized and demonstrated reliable intra-operative neuromonitoring signals of internal anal sphincter activity with significant increase during pelvic autonomic nerve stimulation [0.5 μV (interquartile range = 0.3–0.7) vs 4.8 μV (interquartile range = 2.5–7.5) ;P