Jürgen Zanow

Hemodynamic aspects of reduced platelet adhesion on bioinspired microstructured surfaces.

Occlusion by thrombosis due to the absence of the endothelial cell layer is one of the most frequent causes of failure of artificial vascular grafts. Bioinspired surface structures may have a potential to reduce the adhesion of platelets contributing to hemostasis. The aim of this study was to investigate the hemodynamic aspects of platelet adhesion, the main cause of thrombosis, on bioinspired microstructured surfaces mimicking the endothelial cell morphology. We tested the hypothesis that platelet adhesion is statistically significantly reduced on bioinspired microstructured surfaces compared to unstructured surfaces. Platelet adhesion as a function of the microstructure dimensions was investigated under flow conditions on polydimethylsiloxane (PDMS) surfaces by a combined experimental and theoretical approach. Platelet adhesion was statistically significantly reduced (by up to 78%; p≤0.05) on the microstructured PDMS surfaces compared to that on the unstructured control surface. Finite element method (FEM) simulations of blood flow dynamic revealed a micro shear gradient on the microstructure surfaces which plays a pivotal role in reducing platelet adhesion. On the surfaces with the highest differences of the shear stress between the top of the microstructures and the ground areas, platelet adhesion was reduced most. In addition, the microstructures help to reduce the interaction strength between fluid and surfaces, resulting in a larger water contact angle but no higher resistance to flow compared to the unstructured surface. These findings provide new insight into the fundamental mechanisms of reducing platelet adhesion on microstructured bioinspired surfaces and may lay the basis for the development of innovative next generation artificial vascular grafts with reduced risk of thrombosis.

In vitro testing of a newly developed arteriovenous double-outflow graft

INTRODUCTION The long-term prognosis of arteriovenous polytetrafluoroethylene (PTFE) hemodialysis grafts remains poor, causing significant morbidity and costs. The high failure rate is due to a stenosis development of the graft-vein anastomosis, consisting of two pathophysiologically separate and characteristic lesions emerging from two main mechanisms: development of intimal hyperplasia in the vein and pseudointima in the graft. We developed a new venous anastomotic graft design that combines a flow diffuser and flow division, thereby creating a double-channel graft (Bi-Flow graft) and tested it in vitro. METHODS In vitro experiments have been performed using silastic models of six different anastomotic configurations (straight end-to-side, cuffed Venaflo-type, large and small diffuser, and large and small Bi-Flow) inserted into a pulsatile-flow circuit. The silastic models were created using a computerized numerical control design approach, varying only the venous anastomoses. Velocity fields and shear stresses were obtained using particle image velocimetry, and volumetric flow rates through the models were measured using an ultrasound flowmeter. RESULTS The hooded graft configurations showed significantly lower shear forces than did the end-to-side anastomosis. The shear stresses in the straight end-to-side graft were as high as arterial wall stresses. Large separation areas were present in the hooded grafts, except for the small Bi-Flow graft, which showed only isolated separation zones near the baffle used to divide the flow. The double-channel grafts exhibited a parabolic flow profile consisting of laminar flow in the double-outflow portion of the models laminar flow pattern through the venous anastomosis. A marked flow separation was present in the large Bi-Flow model. Volumetric flow measurements revealed an average flow increase of 21% through the small Bi-Flow graft, which was attributed to the optimization of flow dynamics and pattern within the venous anastomosis of the double-channel graft. CONCLUSION The new arteriovenous Bi-Flow graft design addresses two major problems responsible for the development of venous stenosis of prosthetic hemodialysis grafts in vitro. The new graft design should be further investigated in animal studies.

Quantitative characterization of endothelial cell morphologies depending on shear stress in different blood vessels of domestic pigs using a focused ion beam and high resolution scanning electron microscopy (FIB-SEM)

Microstructured surfaces mimicking the endothelial cell (EC) morphology is a new approach to improve the blood compatibility of synthetic vascular grafts. The ECs are capable of changing their shapes depending on different shear conditions. However, the quantitative correlation between EC morphology and shear stress has not yet been investigated statistically. The aim of this study was to quantitatively investigate the morphology of ECs in dependence on the shear stress. Blood flow rates in different types of natural blood vessels (carotid, renal, hepatic and iliac arteries) originated from domestic pigs were first measured in vivo to calculate the shear stresses. The EC morphologies were quantitatively characterized ex vivo by imaging with high resolution scanning electron microscopy (SEM) and cross-sectioning of the cells using a state-of-the-art focused ion beam (FIB). The relationships between EC geometrical parameters and shear stress were statistically analyzed and found to be exponential. ECs under high shear stress conditions had a longer length and narrower width, i.e. a higher aspect ratio, while the cell height was smaller compared to low shear conditions. Based on these results, suitable and valid geometrical parameters of microstructures mimicking EC can be derived for various shear conditions in synthetic vascular grafts to optimize blood compatibility.

In vivo assessment of the hepatic microcirculation after mesenterico-portal bypass (REX-shunt) using orthogonal polarization spectral imaging.

Background: Extrahepatic portal vein thrombosis, not associated with cirrhosis or tumours, is the second most frequent cause of portal hypertension worldwide. Especially in children, anatomic mesenterico‐portal interposition (REX‐shunt) has become an established treatment. The changes in hepatic microcirculation after reperfusion of the shunt have not been investigated so far.

[Liver transplantation with living donor : current aspects, perspectives and significance in Germany].

More than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.ZusammenfassungVor mehr als 20 Jahren wurde die Lebertransplantation mit Lebendspenden in die Klinik eingeführt. Zunächst für Kinder und später auch für erwachsene Empfänger wurden Spezifika dieser Methode insbesondere in Regionen, die nicht über ein postmortales Programm der Lebertransplantation verfügen, entwickelt. Der sensibelste Punkt der Lebendspende, die Gefährdung eines gesunden Verwandten für die Realisierung der Transplantation, ist systemimmanent und stellt sie damit klar hinter die Möglichkeit einer postmortalen Organspende. Nach weltweiter anfänglicher Euphorie ist sie im neuen Jahrtausend in der westlichen Welt zahlenmäßig deutlich zurückgegangen. Insbesondere in den Ländern Asiens wurde intensiv an der Optimierung gearbeitet, sodass die Sicherheit für den Spender und die Ergebnisqualität für den Empfänger in großen Patientenserien überzeugend gezeigt werden konnten. Der bis heute bestehende eklatante Spenderorganmangel und die Möglichkeit durch die Lebendspende individuell ein optimales (Teil-)Organ zu allozieren, haben die Diskussion über die weitere Profilierung der Lebendspende auch bei uns wieder aktualisiert. Mit der Novelle des deutschen Transplantationsgesetzes im Sommer 2012 wurde eine Reihe versicherungsrechtlicher Voraussetzungen für Lebendspender fixiert. Aktueller Stand und Perspektiven werden hier vorgestellt.AbstractMore than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.

Prostaglandin application improves macro- and microcirculation after aorto-hepato-mesenteric bypass in chronic mesenteric ischemia

Chronic mesenterial ischemia (CMI) is an uncommon cause of abdominal afflictions. The spectrum of therapeutic options ranges from mesenteric artery angioplasty and stenting to surgical revascularization. We used orthogonal polarization spectral (OPS) imaging to assess microcirculation after revascularization of the celiac artery and the superior mesenteric artery. Furthermore, we applicated a prostaglandin I2 derivate (iloprost, Ilomedin®, BayerVital GmbH, Leverkusen, Germany) after bypass reperfusion and demonstrated the effect of this vasodilatative agent to microcirculatory parameters. Our patient was a 52-year-old woman who suffered from a complete obstruction of the celiac artery as well as high-grade stenosis of the superior mesenteric artery (SMA). Therefore, we performed an open revascularization using the greater saphenous vein of the left thigh as graft (reversed vein bypass from the supraceliac aorta sequentially to the celiac artery (termino-lateral anastomosis) and the superior mesenteric artery (termino-terminal anastomosis)). After bypass reperfusion, we administered 3 μg iloprost as bolus directly into the bypass. The agreement of the patient was obtained before the aforementioned procedure and the measurements. Immediately following laparotomy, bypass reperfusion and iloprost administration, we measured the microcirculation of stomach, pancreas, small intestine and right hemi-colon. Microhemodynamic analysis included the quantitative analysis of capillary diameter (D), functional capillary density (FCD) and red blood cell velocity (RBCV). Using these parameters, we calculated the individual capillary volumetric flow rate (capillary blood flow (CBF); in picoliter/s; pl/s) and the perfusion index (PI).

Multimodal imaging of aortoiliac occlusive disease with three‐dimensional postprocessing of PET angiography and CT

Two patients with aortoiliac occlusive disease underwent dynamic and late-static positron emission tomography/computed tomography (PET/CT) acquisitions with 257 and 244 MBq F-18 FDG (CT scan parameters 50 mAs, 120 kV, pitch 1.25). Three-dimensional reconstructions revealed an occluded aortic stent and a high-grade aortic stenosis and demonstrated the relations of vascular pathologies to adjacent structures. Early-dynamic PET can be performed without additional radioactive tracer and may be valuable for evaluation and intervention planning in patients with contraindications to other angiographic modalities.

Lebertransplantation mit Lebendspende

More than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.ZusammenfassungVor mehr als 20 Jahren wurde die Lebertransplantation mit Lebendspenden in die Klinik eingeführt. Zunächst für Kinder und später auch für erwachsene Empfänger wurden Spezifika dieser Methode insbesondere in Regionen, die nicht über ein postmortales Programm der Lebertransplantation verfügen, entwickelt. Der sensibelste Punkt der Lebendspende, die Gefährdung eines gesunden Verwandten für die Realisierung der Transplantation, ist systemimmanent und stellt sie damit klar hinter die Möglichkeit einer postmortalen Organspende. Nach weltweiter anfänglicher Euphorie ist sie im neuen Jahrtausend in der westlichen Welt zahlenmäßig deutlich zurückgegangen. Insbesondere in den Ländern Asiens wurde intensiv an der Optimierung gearbeitet, sodass die Sicherheit für den Spender und die Ergebnisqualität für den Empfänger in großen Patientenserien überzeugend gezeigt werden konnten. Der bis heute bestehende eklatante Spenderorganmangel und die Möglichkeit durch die Lebendspende individuell ein optimales (Teil-)Organ zu allozieren, haben die Diskussion über die weitere Profilierung der Lebendspende auch bei uns wieder aktualisiert. Mit der Novelle des deutschen Transplantationsgesetzes im Sommer 2012 wurde eine Reihe versicherungsrechtlicher Voraussetzungen für Lebendspender fixiert. Aktueller Stand und Perspektiven werden hier vorgestellt.AbstractMore than 20 years ago living donor liver transplantation was introduced into clinical practice. Specifics of this method were developed initially for children and later on for adults particularly in regions where a liver transplantation program using deceased donors was not readily available. The most sensitive aspect of living donation, namely the danger to a healthy relative in order to perform the transplantation is immanent in the system and, thus, it is definitively a secondary option as compared to deceased organ donation. Following worldwide initial euphoria the numbers have markedly decreased in the western world since the start of the new millennium. In Asian countries in particular, much work has been done to optimize the procedure so that the donor safety and the outcome quality for the recipient have been impressively demonstrated in large patient populations. There is still a severe donor organ shortage and the option to allocate an optimal (partial) organ on an individual basis by living donation has given new impact to the discussion about a further rise in the profile of living donations here as well. The new version of the German transplantation legislation implemented in summer 2012 requires a number of conditions with respect to insurance for living donors. The current state and perspectives are presented here.

Acute Stroke Treatment by Surgical Recanalization of Extracranial Internal Carotid Artery Occlusion: A Single Center Experience

Ischemic stroke due to an acute occlusion of the extracranial internal carotid artery (eICA) is associated with high morbidity and mortality. The best treatment option remains unclear. This study aims to increase the available therapeutic experience documented for surgical recanalization of acute eICA occlusions. We retrospectively reviewed all hospital records of the University Hospital Jena between 2006 and 2018 to identified patients with acute ischemic stroke due to an occlusion of the eICA who underwent emergent surgical recanalization. We analyzed clinical data, surgical reports, imaging data, and outpatient records. The primary outcome parameter was the modified Rankin Scale (mRS) at 3 months. During the survey, 12 patients (mean age: 62.3 ± 10.8 years; range: 35-87) underwent emergent surgical recanalization for an acutely symptomatic eICA occlusion. All patients presented with neurological deficits with a mean National Institutes of Health Stroke Scale score at admission of 15.0 ± 5.1 (range 2-23). Patients were selected for surgery mainly due to the extent of the perfusion mismatch, while stroke severity and age were also considered. The median time from symptom onset to surgery was 309 ± 122 minutes (range 112-650 minutes). Complete recanalization was obtained in all 12 patients. No patient deteriorated postoperatively, no intracranial hemorrhage was observed, and no patient died in the following 3 months. Favorable outcomes (mRS: 0-2) after 3 months were achieved in 7 of 12 patients. The current study adds support to previous findings that the surgical recanalization of acute eICA occlusions is a possible and safe treatment option. However, a critical patient selection based on mismatch size in perfusion imaging is crucially important for successful treatment.

Bowel Ischemia in ICU Patients: Diagnostic Value of I-FABP Depends on the Interval to the Triggering Event

Background Intestinal fatty acid-binding protein (I-FABP) has been shown to be of high diagnostic value in patients with acute mesenteric ischemia. Whether these results can be reproduced in critically ill patients on the ICU was to be investigated. Materials and Methods I-FABP was measured in serum and urine of 43 critically ill patients in ICU when mesenteric ischemia was suspected. Bowel ischemia was confirmed in 21 patients (group 1). 22 patients who survived at least seven days without confirmation of ischemia were assigned to group 2. I-FABP levels were compared between the groups, and interval from the event that has triggered ischemia to I-FABP measurement was recorded. Results For the identification of patients with mesenteric ischemia, sensitivity, specificity, and area under the curve (AUC) for serum and urine I-FABP were 33.3%, 95.5%, and 0.565 and 81.3%, 70.0%, and 0.694, respectively. I-FABP measurements performed within 12 to 48 h after the event that triggered ischemia showed a sensitivity, specificity, and AUC for serum and urine of 75%, 100%, and 0.853 and 100%, 73.3%, and 0.856, respectively. Conclusions In ICU patients, one single I-FABP measurement at the time of clinical suspicion failed to reliably detect or exclude mesenteric ischemia. A higher diagnostic value of I-FABP was only confirmed in the early stages of mesenteric ischemia. I-FABP may be used most appropriately in perioperative monitoring.