Recent studies have revealed an important role for LTBP-4 in elastogenesis. Its mutational inactivation in humans causes autosomal recessive cutis laxa type 1C (ARCL1C), which is a severe disorder caused by defects of the elastic fiber network. Although the human gene involved in ARCL1C has been discovered based on similar elastic fiber abnormalities exhibited by mice lacking the short Ltbp-4 isoform (Ltbp4S−/−), the murine phenotype does not replicate ARCL1C. We therefore inactivated both Ltbp-4 isoforms in the mouse germline to model ARCL1C. Comparative analysis of Ltbp4S−/− and Ltbp4-null (Ltbp4−/−) mice identified Ltbp-4L as an important factor for elastogenesis and postnatal survival, and showed that it has distinct tissue expression patterns and specific molecular functions. We identified fibulin-4 as a previously unknown interaction partner of both Ltbp-4 isoforms and demonstrated that at least Ltbp-4L expression is essential for incorporation of fibulin-4 into the extracellular matrix (ECM). Overall, our results contribute to the current understanding of elastogenesis and provide an animal model of ARCL1C.

Objective: Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential. The aim was to investigate mechanical characteristics of modified second-generation BNC tubes, to evaluate in vivo performance and biocompatibility, and to analyze patency rates.Methods: We replaced the right carotid artery of 23 sheep with second-generation BNC tubes. Compared with our firstgeneration tubes, tubes were modified with different surface properties and diminished wall thickness (inner diameter, 4.0-5.0 mm; wall thickness, 1.0-2.5 mm; length, 100 mm) to generate a smoother inner surface with reduced thrombogenic potential and a more porous outer zone, allowing easier cell immigration.Results: At the end of the investigational period, BNC tubes were explanted and grafts were processed for histopathologic analysis. Histologic analysis revealed no acute signs of foreign body reaction such as immigration of giant cells or other acute inflammatory reaction and therefore provided evidence for good biocompatibility of the second-generation tubes. However, all grafts of the sheep without antiplatelet therapy were occluded after 9 months, whereas grafts in sheep receiving dual platelet inhibition showed a patency rate of 67% (six of nine grafts). Further modified grafts revealed a patency rate of 80% (four of five grafts remained open).Conclusions: Patency rates of the second-generation tubes could be substantially improved compared with our firstgeneration tubes. However, poor patency rates of tissue-engineered blood vessels still limit their use in clinical studies. Further efforts in terms of in vitro and in vivo studies are essential to improve grafts of BNC.

Hypothermia is a severe, unpleasant side effect during general anesthesia. Thus, temperature surveillance is a prerequisite in general anesthesia settings during experimental surgeries. The gold standard to measure the core body temperature (Tcore) is placement of a Swan-Ganz catheter in the pulmonary artery, which is a highly invasive procedure. Therefore, Tcore is commonly examined in the urine bladder and rectum. However, these procedures are known for their inaccuracy and delayed record of temperatures. Zero-heat-flux (ZHF) thermometry is an alternative, non-invasive method quantifying Tcore in human patients by applying a thermosensoric patch to the lateral forehead. Since the porcine cranial anatomy is different to the human’s, the optimal location of the patch remains unclear to date. The aim was to compare three different patch locations of ZHF thermometry in a porcine hypothermia model. Hypothermia (33.0°C Tcore) was conducted in 11 anesthetized female pigs (26-30kg). Tcore was measured continuously by an invasive Swan-Ganz catheter in the pulmonary artery (Tpulm). A ZHF thermometry device was mounted on three different defined locations. The smallest average difference between Tpulm and TZHF during stable temperatures was 0.21 ± 0.16°C at location A, where the patch was placed directly behind the eye. Also during rapidly changing temperatures location A showed the smallest bias with 0.48 ± 0.29°C. Location A provided the most reliable data for Tcore. Therefore, the ZHF thermometry patch should be placed directly behind the left temporal corner of the eye to provide a non-invasive method for accurate measurement of Tcore in pigs.

Background An open abdomen is often necessary for survival of patients after peritonitis, compartment syndrome, or in damage control surgery. However, abdominal wall retraction relieves delays and complicates abdominal wall closure. The principle of the newly fascia preserving device (FPD) is the application of anteriorly directed traction on both fascial edges over an external support through a longitudinal beam to relieve increased abdominal pressure and prevent fascial retraction. Methods Twelve pigs were randomly divided into two groups. Both groups underwent midline laparotomy under general anesthesia. Group one was treated with the new device, group two served as controls. The tension for closing the abdominal fascia was measured immediately after laparotomy as well as at 24 and 48 h. Vital parameters and ventilation pressure were recorded. Post mortem, all fascial tissues were histologically examined. Results All pigs demonstrated increases in abdominal circumference. In both groups, forces for closing the abdomen increased over the observation period. Concerning the central closing force after 24 h we saw a significant lower force in the FPD group (14.4 ± 3 N) vs. control group (21.6 ± 5.7 N, p < 0.001). By testing the main effects using an ANOVA analysis we found a significant group related effect concerning closing force and abdominal circumference of the FDP-group vs. control group ( p < 0.001; p < 0.001). The placement of the device on chest and pelvis did not influence vital parameters and ventilation pressure. Histologic exam detected no tissue damage. Conclusions This trial shows the feasibility to prevent fascial retraction during the open abdomen by using the new device. Thus, it is expected that an earlier closure of the abdominal wall will be possible, and a higher rate of primary closure will be attained.

BackgroundContribution of the small intestine to systemic inflammation after cardiac arrest (CA) is poorly understood. The objective was to evaluate whether an in vivo rat model of 6 min CA is suitable to initiate intestinal ischaemia-reperfusion-injury and to evaluate histomorphological changes and inflammatory processes in the small intestinal mucosa resp. in sera.MethodsAdult male Wistar rats were subjected to CA followed by cardio-pulmonary resuscitation. Proximal jejunum and serum was collected at 6 h, 24 h, 72 h and 7 d post return of spontaneous circulation (ROSC) and from a control group. The small intestine was evaluated histomorphologically. Cytokine concentrations were measured in jejunum lysates and sera.ResultsHistomorphological evaluation revealed a significant increase in mucosal damage in the jejunum at all timepoints compared to controls (p < 0.0001). In jejunal tissues, concentrations of IL-1α, IL-1β, IL-10, and TNF-α showed significant peaks at 24 h and were 1.5- to 5.7-fold higher than concentrations at 6 h and in the controls (p < 0.05). In serum, a significant higher amount of cytokine was detected only for IL-1β at 24 h post-ROSC compared to controls (15.78 vs. 9.76 pg/ml).ConclusionCA resulted in mild small intestinal tissue damage but not in systemic inflammation. A rat model of 6 min CA is not capable to comprehensively mimic a post cardiac arrest syndrome (PCAS). Whether there is a vital influence of the intestine on the PCAS still remains unclear.Electronic supplementary materialThe online version of this article (10.1186/s12871-018-0530-8) contains supplementary material, which is available to authorized users.