The modulation of endothelial glycocalyx by sulodexide on the porcine model of enzymatic endothelial glycocalyx damage - a pilot study.

David Astapenko, Diana Gorskaja, Marek Zrzavecky, Hanako Kawashima, Edward Ssali, Pavel Navratil, Ludek Hana, Jan Motesicky, Vera Radochova, Radomir Hyspler, Alena Ticha, Christian Lehmann, Manu Lng Malbrain, Zdenek Zadak, Vladimir Cerny
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Abstract

BackgroundSulodexide is a glycosaminoglycan-based drug prescribed to patients with angiopathy. We performed a pilot study to investigate whether sulodexide positively modulates the endothelial glycocalyx (EG) layer and the microcirculation in a porcine model of EG enzymatic damage. The EG is a sugar-based endothelial lining that is involved in the physiology of the capillary wall and the pathogenesis of many diseases.MethodsEG damage was induced in eight piglets by hyaluronidase III and heparanase I given intravenously. Four animals received sulodexide 600 IU intravenously before the enzymes and four animals after the enzymes were administered. Four animals constituted a control group. Sublingual microcirculation by side-stream dark field imaging and plasmatic concentration of syndecan-1 by ELISA were measured at baseline, 20 min after intervention, and at the 40th, and 60th minute onwards. The statistics were performed with a one-way ANOVA test with Turkey's correction for multiple comparisons testing. Timepoint comparison was performed by Student t-test or Mann-Whitney test.ResultsAt baseline, there were no statistically significant differences between the animal groups. After the intervention, the levels of syndecan-1 were significantly lower in the control group. While there were no differences between the two intervention groups. The sublingual microcirculation analysis showed that the DeBacker score was significantly higher in the control group. At 60 min, there was also a statistically significant difference in DeBacker score between the groups (8.1 ± 1.6 mm-1 in the group with enzymes given first and 11 ± 0.92 mm-1 in the group with sulodexide given first, p = 0.03). The analysis of the proportion of perused vessels did not show any statistically significant differences.ConclusionThe results of the study demonstrated a working model of EG damage but no specific action of sulodexide on EG modulation. In the sublingual microcirculation analysis, the sulodexide reduced the fall in absolute tissue perfusion in 60 min.

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舒洛地特对猪酶促内皮糖萼损伤模型内皮糖萼的调节-一项初步研究。
背景:舒洛地特是一种以糖胺聚糖为基础的药物,用于血管病变患者。我们进行了一项初步研究,以调查苏洛地特是否积极调节内皮糖萼(EG)层和EG酶损伤猪模型的微循环。EG是一种糖基内皮细胞,参与毛细血管壁的生理和许多疾病的发病机制。方法:采用静脉注射透明质酸酶III和肝素酶I诱导8头仔猪EG损伤。4只动物在给酶前静脉注射舒洛地特600 IU, 4只动物在给酶后静脉注射舒洛地特。4只动物作为对照组。在基线、干预后20分钟、干预后第40分钟和60分钟分别采用侧流暗场成像法检测舌下微循环和ELISA法检测血浆syndecan-1浓度。统计数据采用单因素方差分析检验,土耳其对多重比较检验进行校正。时间点比较采用Student t检验或Mann-Whitney检验。结果:在基线时,动物组间无统计学差异。干预后,对照组syndecan-1水平明显降低。而两个干预组之间没有差异。舌下微循环分析显示,对照组DeBacker评分明显高于对照组。60 min时,两组DeBacker评分差异也有统计学意义(先给酶组为8.1±1.6 mm-1,先给舒洛地特组为11±0.92 mm-1, p = 0.03)。细读血管比例分析无统计学差异。结论:研究结果证实了脑电损伤的工作模型,但苏洛地特对脑电的调节没有特异性作用。在舌下微循环分析中,舒洛地特在60min内减少了绝对组织灌注的下降。
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