Prevention of ischemia-reperfusion injury on the porcine model of supra-renal aortic clamp by sulodexide

医学 微循环 管周毛细血管 糖萼 泌尿科 血栓调节蛋白 再灌注损伤 缺血 蛋白尿 内科学 麻醉 病理 肾 血小板 免疫学 凝血酶
作者
Ludek Hana,Katerina Tlapakova,Dana Čížková,Alena Tichá,Christine Lehmann,Vladimír Černý,Robert G. Hahn,Jaromír Kočí,David Astapenko
出处
期刊:Clinical Hemorheology and Microcirculation [IOS Press]
卷期号:89 (3): 260-269
标识
DOI:10.1177/13860291241306568
摘要

Background The ischemia-reperfusion injury (IRI) is unavoidable in vascular surgery. Damage to the microcirculation and endothelial glycocalyx might set up a shock with loss of circulatory coherence and organ failure. Sulodexide may help to protect endothelial glycocalyx and alleviate the ischemia-reperfusion injury. Methods Twenty female piglets underwent surgery with a 30-min-long suprarenal aortic clamp, followed by two hours of reperfusion. Ten piglets received sulodexide before the clamp, and 10 received normal saline. Blood and urine samples were taken at baseline and in 20-min intervals until the 120 th minute to analyze the serum syndecan-1, E-selectin, and thrombomodulin. Albumin and glycosaminoglycans were examined in the urine. The kidney biopsies before and after the protocol were examined by light microscopy with hematoxylin-eosin staining. The sublingual microcirculation was recorded by side-stream dark field imaging at the time as blood and urine. Results Based on the 2-way ANOVA testing, there was no statistically significant difference in the parameters of sublingual microcirculation. Serum markers of endothelial cell activation and damage (E-selectin and thrombomodulin) did not show any statistically significant difference either. Syndecan-1, a marker of glycocalyx damage, showed statistically significantly higher values based on the 2-way ANOVA testing (p < 0.0001) with the highest difference in the 80 th minute: 7.8 (3.9–44) ng/mL in the control group and 1.8 (0.67–2.8) ng/mL in the sulodexide group. In the urine, the albuminuria was higher in the control group, although not statistically significant. Glycosaminoglycans were statistically significantly higher in the sulodexide group based on the mixed-effect analysis due to the intervention itself. Histological analysis of the renal biopsies showed necrosis in both groups after reperfusion. Conclusion Administering sulodexide significantly reduced the level of endothelial markers of IRI. The study results support further research into using preemptive administration of sulodexide to modulate IRI in clinical medicine.
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