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Objective The impact of stent design on venous patency is not well studied. The purpose of this study was to investigate the effect of stent material burden on endothelial coverage of stented venous segments, which may contribute to vessel healing and patency. Methods Segmented self expanding bare nitinol stents (18 × 50 mm) comprising 5 mm long attached metallic rings separated by 2, 5, or 8 mm gaps were implanted in the inferior vena cava (IVC) of 10 sheep. These stents were designed and manufactured for the purposes of this study. At six, 12, and 24 weeks after implantation the animals were euthanised and the stented vessels harvested for histomorphometric analysis. Three sections from the metallic part as well as the gaps between the struts were reviewed for quantification of endothelialisation after six, 12, and 24 weeks. The intimal thickness over and between the stent struts was measured. The endothelialisation score (graded from 1 for complete luminal endothelialisation to 5 for absence of endothelial cells) was determined. Results All stents were successfully deployed and all 10 sheep survived until the time of harvesting. Macroscopic inspection after 24 weeks showed only partial endothelialisation over stents with 2 mm and 5 mm skipped segments, whereas the stents with 8 mm skipped segments were totally incorporated into the vein wall. After 24 weeks, the mean (SD) neointimal thicknesses over stent struts with 2 mm, 5 mm, and 8 mm skipped segments were 254.0 (51.6), 182.2 (98.1), and 194.6 (101.1) μm, respectively. Comparison of endothelialisation scores of stents over time showed statistically significantly better endothelialisation over stents with 8 mm gaps after 12 and 24 weeks. Conclusion Stent designs providing structural support to veins with larger gaps between the scaffold material appear to lead to faster and more complete endothelialisation as well as a thinner intimal layer.

The aim of this study was to compare two variants of a novel polycarbonate polyurethane prosthesis with polyethylene terephthalate (Dacron) prosthesis in an established sheep model of carotid patch angioplasty. Two variants of the polycarbonate polyurethane prosthesis were used: (1) Polycarbonate polyurethane equal (PCU-e) prosthesis consisted of a multilayered porous structure with equal internal and external layers; (2) Polycarbonate polyurethane with more porous inner layers (PCU-mp) prosthesis had more porous inner layers than external layers. Carotid patch angioplasty was performed in 12 sheep: in six sheep, the PCU-e variant and in the other six sheep, the PCU-mp variant was implanted. Dacron patches were implanted in the contralateral carotid artery of all sheep as a control. Half of the animals with each polycarbonate polyurethane variant were euthanized after two weeks and the other half after eight weeks. Cellular infiltration, endothelialization, and neointimal hyperplasia were examined. All grafts were patent, and no thrombus was seen in any of the harvested arteries. The pores of all the three patch materials allowed infiltration of inflammatory cells, capillaries, and connective tissue. After eight weeks, a nearly complete endothelialization was visible in all patch groups without an obvious difference between the three patch materials. The neointima was thinner in the PCU patches (PCU-e: 56 +/- 13 mu m, PCU-mp: 119 +/- 60 mu m) when compared to Dacron patches (156 +/- 64 mu m) after two weeks. After 8 weeks, a further neointimal growth was detectable, without any significant difference of neointimal thickness between the three patch materials (Dacron: 274 +/- 82 mu m, PCU-e: 324 +/- 98 mu m, PCU-mp: 235 +/- 59 mu m). With the novel polycarbonate polyurethane patch materials, we achieved promising functional and morphological results with 100% patency and nearly complete endothelialization. Our findings showed at least a non-inferiority of the novel polycarbonate polyurethane patch material compared to Dacron. There were no significant differences detected between the two polycarbonate polyurethane patch variants.

Scientific reports 9, 18153 (2019). doi:10.1038/s41598-019-54541-z, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Background In vascular surgery, novel synthetic prosthesis materials for patch-angioplasties, interpositions, bypasses and shunts are continuously under development and optimization. The characteristics of an ideal vascular prosthesis would display long-term patency, biocompatibility, durability, low porosity, lack of stich hole bleeding, ease of handling, kink resistance, infection resistance and reasonable costs. The aim of this study was to establish and report a reliable sheep model including potential pitfalls where those parameters could be analyzed. Before surgery, sheep were acclimatized for 4–8 weeks, during which parasite infections were treated and blood and serum parameters monitored. Twenty-four sheep underwent surgery, and carotid patch-angioplasties (n = 12), graft interpositions (n = 6) or arteriovenous prosthetic shunts (n = 6) were implanted. Half of the animals in each group were sacrificed after 2 weeks and the other half after 8 weeks. The implants were analyzed for patency, endothelialization, thrombogenicity and biocompatibility by clinical observation, blood flow measurement and pathological and histopathological (H&E, EvG) as well as immunohistochemical (Ki67, CD31) evaluations. Results Health monitoring of the sheep revealed a parasitic burden with endoparasites in all animals. Some animals showed thereby infestations in the bile duct causing fibrotic cholangitis with calcifications in the liver. In addition, sarcosporidia were detected in histopathological specimen of the heart in all animals. Parasitic burden correlated with blood counts and serum bilirubin levels. Both were significantly reduced by albendazole treatment within the acclimatization time. Patches, interposition grafts, and straight shunts were successfully implanted bilaterally in all animals. The total average operation time was 136 ± 21 min. Most animals (23/24) showed good patency rates and general condition after implantation. Pathological and histopathological/immunohistochemical analyses were suitable to determine thrombogenicity, endothelialization, cellular/fibroblastic proliferation, biocompatibility, inflammatory cell infiltration, and thickness of neointima in the prosthesis material. Conclusions We have developed a suitable experimental protocol with standardized and successful anesthesia- and surgical-procedures for patch-angioplasty, graft interposition, and arteriovenous prosthetic shunts. This sheep model allows testing of new prosthetic materials for biocompatibility, thrombogenicity, and endothelialization.

Due to the shortage of suitable organs, the demand for partial liver transplantation from living donors has increased worldwide. N-acetylcysteine (NAC) has shown protective effects as a free radical scavenger during hypothermic preservation and warm ischemia-reperfusion liver injury; however, no study has reported the effects in partial liver transplantation. The aim of this study was to analyze the impact of NAC on liver graft microcirculation and graft function after partial liver transplantation in rats.Orthotopic partial liver transplantations were performed in 40 rats following cold storage in histidine-tryptophan-ketoglutarate solution for 3 h with 20 mM NAC (NAC group, n = 20) or without (control group, n = 20). We assessed portal circulation, graft microcirculation, and biochemical analyses of plasma at 1, 3, 24, and 168 h after portal reperfusion.(Control versus NAC, median and range): Portal venous pressure was significantly lower with NAC (P = 0.03). Microcirculation measured by laser Doppler was significantly improved with NAC throughout the time course (P = 0.003). Alanine aminotransferase levels were significantly lower in the NAC group (P0.05). Total antioxidative capacity was significantly higher in the NAC group at 1 h after reperfusion (Trolox equivalents: median, 3 μM; range, 2.9-6.7 versus median, 16.45 μM; range, 10.4-18.8). Lipid peroxidation was significantly abrogated in the NAC group (median, 177.6 nmol/mL; range, 75.9-398.1 versus median, 71.5 nmol/mL; range, 58.5-79 at 3 h).This study showed that NAC treatment during cold storage resulted in improved microcirculation and preservation quality of partial liver graft likely because of enhanced antioxidant capacity and reduced lipid peroxidation.

Background Due to the drastic shortage of organ donors, clinicians are increasingly considering the use of deceased after cardiac death donors (DCD). Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic bacteria as a cell protectant to survive in harsh environments. We hypothesized that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers. Material and methods Rat livers were harvested from male Wistar rats weighing 250-300 g. Three experimental groups (n=5 per group) were studied: (1) CONTROLS: cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs-Henseleit buffer solution. Results (mean ±SEM, Control vs. DCD vs. DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in DCD+Hydroxyectoine compared to DCD (AST: 9±0.54; 56.8±2.05; 32.2±7.25 U/L, ALT: 9.5±0.5; 37.75±9.6; 17.5±4.17 U/L). Bile production at the end of 45 min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16±1.32; 1.36±0.34; 10.75±2.24 µL/g liver weight/45 min). Malondialdehyde values were significantly lower in DCD+Hydroxyectoine (0.8±0.09, 1.14±0.18, 0.77±0.08 nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in DCD+Hydroxyectoine (219.07±51.79, 431.9±35.70, 205.2±37.71 pg/mL) and the portal venous pressure at 45 min was lower compared to DCD (20.41±0.12, 27.47±0.45, 22.08±0.78 mmHg). Conclusions Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.

Background: Chemotherapy with L-asparaginase is associated with hepatotoxicity resulting in organ dysfunction in patients with preexisting liver disorders. This study investigated the protective effect of L-carnitine during chemotherapy in a steatotic rat liver model. Methods: Livers from nonsteatotic and steatotic rats were tested in an isolated liver reperfusion model adding L-asparaginase and L-carnitine to the reperfusate. Portal venous pressure (PVP), hepatic oxygen consumption, aspartate aminotransferase, lactate dehydrogenase, glutamate dehydrogenase and α-glutathione S-transferase levels were assessed. Further histopathological analysis was performed and cytotoxicity was verified in vitro. Results:L-Asparaginase induced toxicity in fatty livers whereas low toxicity was observed in normal livers. L-Carnitine induced a decline in PVP and oxygen consumption, and reduced parenchymal and mitochondrial damage in fatty livers. Cytotoxicity of L-asparaginase was not impaired by the presence of L-carnitine. Conclusions: Our study emphasizes the potential of L-carnitine to reduce L-asparaginase-induced hepatotoxicity in patients with preexisting liver disorders.

Background Due to the severe shortage of deceased donors, demand for living-donor liver transplantation (LDLT) has increased worldwide. Here, we compared POLYSOL, a recently developed low-viscosity preservation solution, and histidine-tryptophan-ketoglutarate (HTK) for cold storage of partial liver graft in this study. Methods Partial liver transplantations with 30% of the native liver were performed in Lewis rats. The graft livers were flushed with either HTK or POLYSOL (n = 25, respectively) and stored in the respective solution for 3 h at 5°C. Graft function was evaluated regarding ischemia-reperfusion injury and regeneration at 1, 3, 24, and 168 h after reperfusion. Results POLYSOL preservation resulted in improvement of portal venous flow (HTK versus POLYSOL; mean ± SEM: 16.8 ± 2.2 versus 21.6 ± 2.1 mL/min; P = 0.005), microcirculation (383 ± 63 versus 532 ± 64 Flux; P = 0.045), ALT (310.2 ± 56.1 versus 181.8 ± 17.0 IU/L; P = 0.0262), LDH (4052.4 ± 764.4 versus 2494.1 ± 410.0 IU/L; P = 0.0215), total bilirubin (21.6 ± 14.2 versus 4.0 ± 0.6 IU/L; P = 0.0236), malondialdehyde (100.0 ± 4.3 versus 69.2 ± 4.0 nmol/mL; P = 0.0015), as well histologic findings at 24 h. Liver regeneration was improved in POLYSOL with regards to liver weight (4.0 ± 0.2 versus 4.3 ± 0.3 g; P = 0.038) and Ki-67 labeling index (9.67 ± 2.17 versus 1.10 ± 0.14%; P

Hepatitis monthly 16(8), e36821 (2016). doi:10.5812/hepatmon.36821, Published by Tehran

Background/Aim: Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. Materials and Methods: Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4°C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. Results: Data are presented as mean ± SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 ± 5.3, 63.2 ± 17.3, 25.6 ± 3.9, and 82.8 ± 27.3 U/l) and lactate dehydrogenase levels (289.4 ± 41.2, 2,139.4 ± 542.7, 577.2 ± 117.2, and 2,429 ± 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 ± 0.3, 2.7 ± 1, 1.0 ± 0, and 3.9 ± 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 ± 1, 21.2 ± 3.1, 16.1 ± 1, and 23.2 ± 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 ± 0.17, 1.8 ± 0.2, 2.7 ± 0.2, and 2.6 ± 0.1 μmol/l). Bile production levels showed no statistical significance (23.2 ± 3.8, 27.3 ± 1.8, 43.5 ± 18, and 31 ± 2.5 μl/45 min). Conclusion: Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts.

Energy-based technologies for tissue sealing and cutting are increasingly supplementing current standards used for haemostasis and dissection during laparoscopic surgery. For their safe and efficacious use in clinical practice, these instruments have to guarantee sufficient burst resistance and low thermal damage to adjacent tissue in combination with good cutting characteristics.The novel laparoscopic, bipolar electrosurgical sealing and cutting instrument BiCision® was compared to a commercially available laparoscopic device (EnSeal(™)) on visceral and peripheral arteries and veins in an animal model.For all parameters investigated (burst pressure, cut quality, tissue adhering to the instrument, time needed to seal and cut the vessel and thermal damage), BiCision® was at least as good as EnSeal(™). Regarding the burst pressure, BiCision® was superior over EnSeal(™) in arteries: 600 mmHg (±478) versus 241 (±269) mmHg, respectively (p0.0001*). In veins, almost equivalent burst pressures of 155 ± 134 mmHg (BiCision®) and 173 ± 139 mmHg (EnSeal(™)) were obtained.BiCision® appeared to be as good as or even superior to EnSeal(™). Since EnSeal(™) has already been shown to be safe and has been successfully used in clinical practice, BiCision® is assumed to be as efficient and reliable as EnSeal(™) under pre-clinical conditions.

Laparoscopic techniques are increasingly applied for the treatment of diverse gastrointestinal diseases. With regard to reports of a pronounced decrease of intra-abdominal blood flow with increasing intra-abdominal pressure, the present study investigates the impact of pressure and gas type on ischemia in small bowel anastomoses in the rat model. Laparotomy and ileoileal anastomosis were performed in 39 male Sprague-Dawley rats. A CO2 or helium pneumoperitoneum of 3 mm Hg or of 6 mm Hg was maintained before and after anastomoses. Rats in the control group received no pneumoperitoneum. Animals were sacrificed after 5 d, and the anastomotic region was explanted for subsequent histopathological examinations. In hematoxylin and eosin (HE)-stained sections, the Chiu score, villi configuration, and number of goblet cells were analyzed. Proliferation (Ki67) and expression of a matrix metalloproteinase (MMP-8) were examined by immunohistochemistry. Mucosal damage according to the scoring system by Chiu, the number of goblet cells, the villus length, the proliferation (Ki67), and the submucosal expression of MMP-8 was similar in all groups. Our results suggest that within a certain range of pressures and time, laparoscopic assisted surgery using CO2 pneumoperitoneum can be performed safely. Helium gas offers no advantages over CO2.

To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection.Forty-four male Wistar rats were assigned to three groups: (1) control group (CG); (2) bile duct ligation with meloxicam treatment (BDL + M); and (3) bile duct ligation without meloxicam treatment (BDL). Secondary biliary liver cirrhosis was induced via ligature of the bile duct in the BDL + M and BDL groups. After 2 wk, the animals underwent a 50% hepatectomy. In the BDL + M group 15 min prior to the hepatectomy, one single dose of meloxicam was administered. Parameters measured included: microcirculation of the liver and small bowel; portal venous flow (PVF); gastrointestinal (GI) transit; alanine aminotransferase (ALT); malondialdehyde; interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1) and hypoxia-inducible factor 1 alpha (HIF-1α) levels; mRNA expression of cyclooxigenase-2 (COX-2), IL-6 and TGF-β1; liver and small bowel histology; immunohistochemical evaluation of hepatocyte and enterocyte proliferation with Ki-67 and COX-2 liver expression.Proliferative activity of hepatocytes after liver resection, liver flow and PVF were significantly higher in CG vs BDL + M and CG vs BDL group (P0.05), whereas one single dose of meloxicam ameliorated liver flow and proliferative activity of hepatocytes in BDL + M vs BDL group. COX-2 liver expression at 24 h observation time (OT), IL-6 concentration and mRNA IL-6 expression in the liver especially at 3 h OT, were significantly higher in BDL group when compared with the BDL + M and CG groups (P0.01, P0.001, P0.01, respectively). Liver and small bowel histology, according to a semi quantitative scoring system, showed better integrity in BDL + M and CG as compared to BDL group. ALT release and HIF-1α levels at 1 h OT were significantly higher in BDL + M compared to CG and BDL group (P0.001 and P0.01, respectively). Moreover, ALT release levels at 3 and 24 h OT were significantly higher in BDL group compared to CG, P0.01. GI transit, enterocyte proliferative activity and number of goblet cells were in favor of meloxicam treatment vs BDL group (P0.05, P0.001, P0.01, respectively). Additionally, villus length were higher in BDL + M as compared to BDL group.One single dose of meloxicam administered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel.