Nógrády Miklós, Varga Gabriella, Szűcs Szilárd, Kaszaki József, Boros Mihály, Érces Dániel
Sebészeti Műtéttani Intézet, Szegedi Tudományegyetem 6720 Szeged, Szőkefalvi-Nagy Béla u. 6.
Szülészeti és Nőgyógyászati Klinika, Szegedi Tudományegyetem Szeged.
Magy Seb. 2017 Sep;70(3):221-231. doi: 10.1556/1046.70.2017.3.2.
Non-occlusive mesenteric ischemia (NOMI) develops without anatomical causes. Early diagnosis is challenging and treatments are of questionable effectiveness. We investigated the role of complement activation in the pathophysiology of NOMI in animal models through the inhibition of complement C5a.
60-min partial aortic occlusion (PAO; abdominal aorta, proximal to celiac trunk; mean arterial pressure: 30-40 mmHg) was established in Sprague-Dawley rats (n = 28) and 60-min cardiac tamponade in minipigs (n = 19; mean arterial pressure: 40-50 mmHg) to observe short- and long-term circulatory and inflammatory consequences of NOMI. Macro- and microhemodynamics, leukocyte infiltration, plasma levels of inflammatory mediators (endothelin, HMGB-1) were measured. C5a inhibitor (Acetyl-Peptid-A; 4 mg/kg iv) was administered at the 45th min of PAO or tamponade, respectively.
Twenty-four hours after PAO systemic inflammatory response increased cardiac output and superior mesenteric artery flow (SMAF). C5a inhibition reduced the elevated cardiac output (203.1 ± 5 vs 269.6 ± 8.1 ml/min/kg) and SMAF and increased ileal microcirculation (833.5 ± 33.8 vs 441.9 ± 22.4 μm/s). In pigs, after the tamponade, C5a inhibition reduced the immediate hemodynamic disturbances, temporarily increased SMAF and permanently the ileal microcirculation. The Acetyl-Peptid-A treatment reduced leukocyte infiltration and plasma levels of inflammatory mediators in both NOMI models.
Complement activation plays central role in the macro- and microcirculatory disturbance during NOMI. C5a inhibition reduces the inflammatory activation and influences the hemodynamic consequences of experimental NOMI.
非闭塞性肠系膜缺血（NOMI）无解剖学病因。早期诊断具有挑战性，治疗效果也存在疑问。我们通过抑制补体C5a，在动物模型中研究了补体激活在NOMI病理生理学中的作用。
在Sprague-Dawley大鼠（n = 28）中建立60分钟的部分主动脉闭塞（PAO；腹主动脉，腹腔干近端；平均动脉压：30 - 40 mmHg），在小型猪（n = 19；平均动脉压：40 - 50 mmHg）中建立60分钟的心包填塞，以观察NOMI的短期和长期循环及炎症后果。测量宏观和微观血流动力学、白细胞浸润、炎症介质（内皮素、HMGB-1）的血浆水平。分别在PAO或心包填塞的第45分钟给予C5a抑制剂（乙酰肽A；4 mg/kg静脉注射）。
PAO后24小时全身炎症反应增加了心输出量和肠系膜上动脉血流（SMAF）。C5a抑制降低了升高的心输出量（203.1 ± 5 vs 269.6 ± 8.1 ml/min/kg）和SMAF，并增加了回肠微循环（833.5 ± 33.8 vs 441.9 ± 22.4 μm/s）。在猪中，心包填塞后，C5a抑制减轻了即刻血流动力学紊乱，暂时增加了SMAF，并永久性增加了回肠微循环。乙酰肽A治疗降低了两种NOMI模型中的白细胞浸润和炎症介质血浆水平。
补体激活在NOMI期间的宏观和微观循环紊乱中起核心作用。C5a抑制减少了炎症激活，并影响实验性NOMI的血流动力学后果。
