Complement C5a inhibition improves late hemodynamic and inflammatory changes in a rat model of nonocclusive mesenteric ischemia
| Autor: | Miklós Nógrády, Szilárd Szűcs, Dániel Érces, József Kaszaki, Tamás Fischer-Szatmári, Hidechika Okada, Chun Cao, Mihály Boros, András Mészáros, Noriko Okada, Gabriella Varga |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Mean arterial pressure Pathology medicine.medical_specialty Cardiac output Hemodynamics Pilot Projects Statistics Nonparametric Microcirculation Rats Sprague-Dawley Random Allocation 03 medical and health sciences 0302 clinical medicine Ileum medicine Animals HMGB1 Protein Vascular Patency Inflammation Analysis of Variance Microscopy Video Endothelin-1 Tumor Necrosis Factor-alpha business.industry Serine Endopeptidases Rats Disease Models Animal 030104 developmental biology Mesenteric Ischemia 030220 oncology & carcinogenesis Multivariate Analysis Circulatory system Surgery medicine.symptom Splanchnic business Perfusion Biomarkers Vasoconstriction |
| Zdroj: | Surgery. 159:960-971 |
| ISSN: | 0039-6060 |
| Popis: | Background Nonocclusive mesenteric ischemia (NOMI) can evolve in a variety of low-flow states. Although the mechanisms leading to NOMI-related intestinal necrosis are largely unknown, circumstantial evidence suggests that excessive vasoconstriction and complement activation both play important roles in this process. Because targeting of the circulatory malfunction of the splanchnic area could be of therapeutic relevance, we set out to investigate the long-term effects of treatment with a complement C5a antagonist in a rat model of partial aortic occlusion (PAO)-induced transient mesenteric hypoperfusion. Methods The mean arterial pressure of the splanchnic area was kept between 30 and 40 mm Hg by 60 minutes of PAO in anesthetized male Sprague-Dawley rats. C5a inhibitor acetyl-peptide-A (AcPepA; 4 mg kg−1 intravenously) or vehicle administration was initiated at the 45th minute of PAO. After 24 hours, the animals were reanesthetized to record the macrohemodynamics and ileal microcirculation, and plasma and tissue samples were taken for determination of high-mobility group box protein-1 (HMGB-1), endothelin-1, tumor necrosis factor (TNF)-α levels, and small intestinal leukocyte infiltration. Epithelial structural changes were visualized by in vivo confocal laser scanning endomicroscopy. Results At 24 hours after PAO, mean arterial pressure, heart rate, and cardiac output were significantly greater, the intestinal intramural microcirculation was significantly impaired, and plasma HMGB-1, endothelin-1, TNF-α levels, the degree of epithelial damage and leukocyte infiltration was increased. The AcPepA treatment moderated the hemodynamic and microcirculatory changes, and decreased inflammatory activation and histologic signs of mucosal damage. Conclusion C5a inhibition ameliorated the potentially harmful local mesenteric hypoperfusion and global long-term inflammatory consequences of PAO. This approach is of promise for use in NOMI-associated situations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect