1Institute of Surgical Research, University of Szeged, Szeged, Hungary. 2Second Department of Medicine, University of Szeged, Szeged, Hungary. 3Department of Traumatology, University of Szeged, Szeged, Hungary. 4Department of Immunology, Nagoya City University School of Medicine, Nagoya, Japan. 5Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.
Crit Care Med. 2013 Nov;41(11):e344-51. doi: 10.1097/CCM.0b013e31828a6768.
Cardiogenic shock often leads to splanchnic macro- and microcirculatory complications, and these events are linked to local and systemic inflammatory activation. Our aim was to investigate the consequences of complement C5a antagonist treatment on the early circulatory and inflammatory changes in a clinically relevant large animal model of cardiac tamponade.
A randomized, controlled in vivo animal study in a university research laboratory.
Anesthetized, ventilated, and thoracotomized Vietnamese mini pigs (24 ± 3 kg).
Group 1 (n = 6) served as sham-operated control. In group 2 (n = 7), cardiac tamponade was induced for 60 minutes by the administration of intrapericardial fluid, while the mean arterial pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg) after 45 minutes of tamponade.
The macrohemodynamics, including the superior mesenteric artery flow, was monitored; the average red blood cell velocity in the small intestinal mucosa was determined by an intravital orthogonal polarization imaging technique. The whole blood superoxide production, the plasma level of high-mobility group box protein-1 and big-endothelin and the small intestinal myeloperoxidase activity were measured. One hundred eighty minutes after the relief of tamponade, the mean arterial pressure was decreased, while the plasma levels of superoxide, high-mobility group box protein-1, and big-endothelin, and the intestinal myeloperoxidase activity were increased. The administration of acetyl-peptide-A normalized the mean arterial pressure and preserved the cardiac output, while the superior mesenteric artery flow and mucosal average red blood cell velocity were increased significantly, and the plasma superoxide, high-mobility group box protein-1, big-endothelin, and intestinal myeloperoxidase levels were reduced.
These results provide evidence that blockade of the C5a effects significantly influences the acute splanchnic macro- and microhemodynamic complications and decreases the potentially harmful inflammatory consequences of experimental cardiogenic shock.
心源性休克常导致内脏大、微循环并发症，这些事件与局部和全身炎症激活有关。我们的目的是研究补体 C5a 拮抗剂治疗对心脏压塞临床相关大动物模型中早期循环和炎症变化的影响。
在大学研究实验室进行的随机、对照体内动物研究。
麻醉、通气和开胸的越南迷你猪（24±3 公斤）。
第 1 组（n=6）作为假手术对照。第 2 组（n=7）通过心包内液给药诱导心脏压塞 60 分钟，同时保持平均动脉压在 40 至 45mmHg 之间。第 3 组（n=6）在压塞 45 分钟后用补体 C5a 拮抗剂化合物（肽乙酰肽-A，4mg/kg）治疗。
监测宏观血液动力学，包括肠系膜上动脉血流；通过活体正交偏振成像技术测定小肠黏膜的平均红细胞速度。测量全血超氧化物产生、血浆高迁移率族蛋白-1 和大内皮素水平以及小肠髓过氧化物酶活性。压塞解除后 180 分钟，平均动脉压降低，而血浆中超氧化物、高迁移率族蛋白-1 和大内皮素水平以及小肠髓过氧化物酶活性增加。乙酰肽-A 的给药使平均动脉压正常化并维持心输出量，同时肠系膜上动脉血流和黏膜平均红细胞速度显著增加，血浆中超氧化物、高迁移率族蛋白-1、大内皮素和肠髓过氧化物酶水平降低。
这些结果表明，阻断 C5a 作用显著影响急性内脏大、微循环并发症，并降低实验性心源性休克的潜在有害炎症后果。
