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Atherosclerosis is the leading cause of cardiovascular disease, which is responsible for the majority of deaths worldwide. Lack of reproducible and controlled induction of atherosclerotic lesions in preclinical animal models limits atherosclerosis research. Here, we developed the first automated system for vessel wall injury that leads to more homogenous damage and more pronounced atherosclerotic plaque development at low balloon pressure in a rabbit model of atherosclerosis, and used this system to investigate the risk factor interplay. Elevated plasma homocysteine is an independent risk factor for atherosclerosis and is strongly linked to cardiovascular mortality. Already in the absence of hypercholesterolemia, deficiency in vitamins and choline required for homocysteine metabolization results in atherogenic transformation of the aorta i.e. impairment of its biomechanical properties, alteration of collagen organization as well as macrophage and lipid accumulation, and aggravation of atherosclerosis including significantly altered water diffusion and impaired vascular reactivity in its presence.

OBJECTIVES/HYPOTHESIS: To reverse sarcopenia and increase the volumes of atrophied laryngeal muscles by functional electrical stimulation (FES) using a minimal invasive surgical procedure in an aged ovine model. STUDY DESIGN: Prospective animal study. METHODS: A stimulation electrode was placed unilaterally near the terminal adduction branch of the recurrent laryngeal nerve (RLN) adjacent to the right cricothyroid joint. The electrode was connected to an implant located subcutaneously at the neck region. Predesigned training patterns were automatically delivered by a bidirectional radio frequency link using a programming device and were repeated automatically by the implant every other day over 11 weeks in the awake animal. Outcome parameters comprised volumetric measurements based on three-dimensional reconstructions of the entire thyroarytenoid muscle (TAM), as well as gene expression analyses. RESULTS: We found significant increases of the volumes of the stimulated TAM of 11% and the TAM diameter at the midmembranous parts of the vocal folds of nearly 40%. Based on gene expression, we did not detect a shift of muscle fiber composition. CONCLUSIONS: FES of the terminal branches of the RLN is a secure and effective way to reverse the effects of age-related TAM atrophy and to increase volumes of atrophied muscles. LEVEL OF EVIDENCE: NA Laryngoscope, 2018.

Summary Objective The aim of the study was to establish a basic data set of combined functional and anatomical measures of aged sheep larynges using ex vivo models. Combining these two approaches in one and the same larynx is an unmet goal so far yet is important as newer treatment strategies aim to preserve the organ structure and new assessment tools are required. Ovine larynges were used as their dimensions, and muscle fiber type distribution highly resemble the human larynx. Study Design Ex vivo animal study. Methods Larynges of six sheep (~9 years of age) were subjected to ex vivo functional phonatory experiments. Phonatory characteristics were analyzed as a function of longitudinal vocal fold (VF) prestress. Anatomical measurements of the same larynges comprised micro-computed tomography scans followed by three-dimensional (3D) reconstructions. Using specially adapted radiological scan protocols with subsequent 3D reconstruction, muscle volumes, surface areas, and anatomical measurements were computed. Results Increasing longitudinal prestress yielded higher subglottal pressure (P S ) for the same airflow. Quantitative differences to previous studies—such as the increased P S and increased phonation threshold pressure—were detected. We achieved excellent visualization of the laryngeal muscles and framework, resulting in accurate 3D reconstructions for quantitative analysis. We found no significant intraindividual volume differences of the thyroarytenoid muscles. Conclusion The established protocol allows precise functional and anatomical measures. The data created provide a reference data set for upcoming therapeutic strategies (eg, growth factor therapy, functional electrical stimulation) that target essential structures of the VFs such as the laryngeal muscles and/or the VF mucosa.

Objective Mesenchymal stem/stromal cells derived from human term placentas (PMSCs) are novel therapeutic agents and more topical than ever. Here we evaluated the effects of three types of PMSCs on wound healing in an in vivo mouse model: Amnion-derived MSCs (AMSCs), blood vessel-derived MSCs (BV-MSCs) from the chorionic plate and Wharton's jelly-derived MSCs (WJ-MSCs) from the umbilical cord. Methods We topically applied PMSCs onto skin wounds in mice using the dermal substitute Matriderm® as carrier and evaluated wound healing parameters. In addition, we investigated the effects of all PMSC types under co-application with placental endothelial cells (PLECs). After 8 days, we compared the percent of wound closure and the angiogenic potential between all groups. Results AMSCs, BV-MSCs and WJ-MSCs significantly induced a faster healing and a higher number of blood vessels in the wound when compared to controls (Matriderm®-alone). PLECs did not further improve the advantageous effects of PMSC-treatment. Quantitative data and 3D analysis by high resolution episcopic microscopy confirmed a lower density of vessels in Matriderm®/PMSCs/PLECs co-application compared to Matriderm®/PMSCs treatment. Conclusion Results indicate that all three PMSC types exert similar beneficial effects on wound closure and neovascularization in our mouse model. Practice Using Matriderm® as carrier for PMSCs propagates rapid cell migration towards the wound area that allows a fast and clinically practicable method for stem cell application. Implications These promising effects warrant further investigation in clinical trials.

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Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak link of insulin pump therapy. Wear-time considerably varies between patients and the choice of catheter material is based on personal preferences rather than scientific facts. Therefore, we systematically assessed and quantified the inflammatory tissue response to steel versus Teflon CSII catheters over a maximum wear-time of 7 days in swine. Tissue surrounding catheters was analysed using histopathology and quantitative real-time PCR. The area of inflammation increased significantly over time independent of material which was confirmed by an increase in CD68 expression and an increase in mononuclear and neutrophil cell infiltrate around the catheters. We observed substantially higher fibrin deposition (p

Despite the popularity of a simultaneous application of dermal matrices and split-thickness skin grafts, scarce evidence exists about the process of revascularization involved. In this study, we aimed at analyzing the progression of revascularization by high-resolution episcopic microscopy (HREM) in a porcine excisional wound model. Following the surgical procedure creating 5 × 5 cm(2) full-thickness defects on the back, one area was covered with an autologous split-thickness skin graft alone (control group), the other with a collagen-elastin dermal matrix plus split-thickness skin graft (dermal matrix group). Two skin biopsies per each group and location were performed on day 5, 10, 15, and 28 postoperatively and separately processed for H&E as well as HREM. The dermal layer was thicker in the dermal matrix group vs. control on day 5 and 28. No differences were found for revascularization by conventional histology. In HREM, the dermal matrix did not appear to decelerate the revascularization process. The presence of the dermal matrix could be distinguished until day 15. By day 28, the structure of the dermal matrix could no longer be delineated and was replaced by autologous tissue. As assessed by conventional histology and confirmed by HREM, the revascularization process was comparable in both groups, notably with regard to the vertical ingrowth of sprouting vessels. The presented technique of HREM is a valuable addition for analyzing small vessel sprouting in dermal matrices in the future.

Silver-containing wound dressings are an integral part of wound therapy in adult and pediatric burn patients. The antimicrobial effect of silver is well known and has been described in numerous studies. Side effects are rarely reported from silver-containing wound care products, even though systemic absorption of silver has been shown by elevated levels of silver in the blood of patients after silver exposure during wound therapy. This animal study investigated the silver levels of blood and in which organs and tissues silver is detectable after long-term application of silver-containing wound dressings after a burn trauma. In male rats, a major full-thickness scald was created on their backs according to a standardized burn model. Two different silver-containing wound dressings (nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied initially and changed every 7 days. Weekly blood drawings revealed an increase of blood silver in week three with significant higher values in the SSF compared with NCS group (Ag μg/kg 135.8 vs. 61.7; means; p ≤ 0.05). Thereafter, the NCS group showed significantly higher blood silver levels than the SSF group at week five (Ag μg/kg 192.3 vs. 81.3; means; p ≤ 0.01) and six (Ag μg/kg 168.2 vs. 32.9; means; p ≤ 0.01). After 6 weeks, the animals were sacrificed, and the organs and tissues were analyzed for their silver content by inductively coupled plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue samples, with higher silver values in parenchymatous organs in the NCS than SSF group (Ag μg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs. 313; means; p ≤ 0.05). Silver was also detectable in brain, testis, lung, heart, and muscle tissue.

Amnion-derived mesenchymal stem cells (AMSC) are a promising tool in regenerative medicine. Here we evaluated the utility of Matrigel and Matriderm as carrier for the topical application of AMSC to mice skin wounds. In both application forms, AMSC promoted neovascularization of the wound area. Matrigel proved as excellent matrix for AMSC and immigrating mouse cells, but the solid Matriderm enabled a more adequate positioning of AMSC into the wound. Although AMSC did not attach to Matriderm, they reliably induced wound reduction. Thus, a combined administration of AMSC/Matriderm could be beneficial to potentiate the encouraging effects on wound healing.

Objective To evaluate the effect of local anaesthesia of the mesovarium on end-tidal isoflurane (F e ′iso) concentration and vital parameters during canine ovariohysterectomy. Study design Prospective, randomized, blinded study. Animals Twenty client-owned dogs undergoing elective ovariohysterectomy. Mean age 1.7 (±0.53, SD) years and mean body weight 21 kg (±5.9, SD). Methods Pre-medication was with intravenous acepromazine (0.02 mg kg−1) and methadone (0.1 mg kg−1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen. One group (n = 10) received local infiltration of the mesovarium with 0.5 mL lidocaine 2% and one group (n = 10) with 0.5 mL NaCl 0.9%. Heart (HR) and respiratory rates (fr), invasive mean arterial blood pressure (MAP) and F e ′isowere recorded. The F e ′iso was adjusted according to changes in HR, RR and MAP. Time points used for comparison were T1 (after induction of anaesthesia before surgery), T2 (after lidocaine infiltration of the mesovarium) and T3 (surgical manipulation of the ovaries). Data were analysed using a mixed model for repeated measurement anova and the Tukey adjustment. Results are presented as mean ± SD; p Results In both groups, HR and fr remained stable at the three time points. Mean values ranged from 84 to 94 beats minute−1 and from 10 to 14 breaths minute−1. The F e ′iso was significantly lower at T3 compared to T1 and mean values ranged from 0.95% to 1.24%. The mean arterial blood pressure was significantly higher at T3 compared to T1 and mean values ranged from 58 to 96 mm Hg. At none of the time points were there significant differences between the two groups for HR, fr, MAP or F e ′iso. Conclusion Neither an isoflurane sparing effect nor a difference in autonomic response to surgery was demonstrated following local anaesthesia of the mesovarium. Clinical relevance There appeared to be minimal benefit from local anaesthesia of the mesovarium during this study.

Despite the popularity of a simultaneous application of dermal matrices and split-thickness skin grafts, scarce evidence exists about the process of revascularization involved. In this study, we aimed at analyzing the progression of revascularization by high-resolution episcopic microscopy (HREM) in a porcine excisional wound model. Following the surgical procedure creating 5 × 5 cm(2) full-thickness defects on the back, one area was covered with an autologous split-thickness skin graft alone (control group), the other with a collagen-elastin dermal matrix plus split-thickness skin graft (dermal matrix group). Two skin biopsies per each group and location were performed on day 5, 10, 15, and 28 postoperatively and separately processed for HE as well as HREM. The dermal layer was thicker in the dermal matrix group vs. control on day 5 and 28. No differences were found for revascularization by conventional histology. In HREM, the dermal matrix did not appear to decelerate the revascularization process. The presence of the dermal matrix could be distinguished until day 15. By day 28, the structure of the dermal matrix could no longer be delineated and was replaced by autologous tissue. As assessed by conventional histology and confirmed by HREM, the revascularization process was comparable in both groups, notably with regard to the vertical ingrowth of sprouting vessels. The presented technique of HREM is a valuable addition for analyzing small vessel sprouting in dermal matrices in the future.

Silver-containing wound dressings are an integral part of wound therapy in adult and pediatric burn patients. The antimicrobial effect of silver is well known and has been described in numerous studies. Side effects are rarely reported from silver-containing wound care products, even though systemic absorption of silver has been shown by elevated levels of silver in the blood of patients after silver exposure during wound therapy. This animal study investigated the silver levels of blood and in which organs and tissues silver is detectable after long-term application of silver-containing wound dressings after a burn trauma. In male rats, a major full-thickness scald was created on their backs according to a standardized burn model. Two different silver-containing wound dressings (nanocrystalline silver [NCS] and silver sulphate foam [SSF]) were applied initially and changed every 7 days. Weekly blood drawings revealed an increase of blood silver in week three with significant higher values in the SSF compared with NCS group (Ag μg/kg 135.8 vs. 61.7; means; p ≤ 0.05). Thereafter, the NCS group showed significantly higher blood silver levels than the SSF group at week five (Ag μg/kg 192.3 vs. 81.3; means; p ≤ 0.01) and six (Ag μg/kg 168.2 vs. 32.9; means; p ≤ 0.01). After 6 weeks, the animals were sacrificed, and the organs and tissues were analyzed for their silver content by inductively coupled plasma mass-spectrometry. Silver was detectable in all analyzed organs and tissue samples, with higher silver values in parenchymatous organs in the NCS than SSF group (Ag μg/kg; spleen: 3,469 vs. 260; kidney: 3,186 vs. 289; liver: 2,022 vs. 313; means; p ≤ 0.05). Silver was also detectable in brain, testis, lung, heart, and muscle tissue.