Bergt Stefan, Gruenewald Matthias, Beltschany Claudia, Grub Andrea, Neumann Tobias, Albrecht Martin, Vollmar Brigitte, Zacharowski Kai, Roesner Jan P, Meybohm Patrick
1Department of Anesthesiology and Critical Care Medicine, University Hospital Rostock, Rostock, Germany.2Department of Anesthesiology and Intensive Care Medicine, Schleswig-Holstein University Hospital, Campus Kiel, Kiel, Germany.3Department of Anesthesiology and Intensive Care Medicine, University Hospital of Cologne, North Rhine-Westphalia, Germany.4Institute for Experimental Surgery, Rostock University, Rostock, Germany.5Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.6Department of Anesthesiology and Intensive Care Medicine, Suedstadt Hospital, Rostock, Germany.
Crit Care Med. 2016 Oct;44(10):e988-95. doi: 10.1097/CCM.0000000000001860.
The fibrin-derived peptide Bβ15-42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bβ15-42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation.
Pig and mouse model of cardiopulmonary resuscitation.
Two university hospitals.
Pigs and mice.
Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bβ15-42 followed by a continuous infusion of 1 mg/kg/hr for 5 hours (pFX06; n = 6) or the control group (pCONTROL; n = 6). Cardiac damage, function, and hemodynamics were recorded up to 8 hours. Mice (n = 52) were subjected to 4-minute cardiac arrest followed by cardiopulmonary resuscitation, and randomized either to two boli of 2.4 mg/kg Bβ15-42 (mFX06; n = 26) or the control group (mCONTROL; n = 26). Fourteen-day survival rate, neurocognitive function, and endothelial integrity (additional experiment with n = 26 mice) were evaluated.
Bβ15-42 reduced cumulative fluid intake (3,500 [2,600-4,200] vs 6,800 [5,700-7,400] mL; p = 0.004) within 8 hours in pigs. In mice, Bβ15-42 improved 14-day survival rate (mFX06 vs mCONTROL; 11/26 vs 6/26; p < 0.05) and fastened neurocognitive recovery in the Water-Maze test (15/26 vs 9/26 mice with competence to perform test; p < 0.05). Bβ15-42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration.
This study confirms the new concept of an important role of fibrin derivatives in global ischemia/reperfusion injury, which can be attenuated by the fibrin-derived peptide Bβ15-42.
纤维蛋白衍生肽Bβ15 - 42（FX06）已被证明可减轻缺血/再灌注损伤。我们检验了Bβ15 - 42能提高心肺复苏后存活率和神经认知恢复的假说。
心肺复苏的猪和小鼠模型。
两家大学医院。
猪和小鼠。
猪（n = 16）经历8分钟心脏骤停。成功复苏的猪（n = 12）被随机分为两组，一组给予3 mg/kg Bβ15 - 42，随后以1 mg/kg/小时的速度持续输注5小时（pFX06组；n = 6），另一组为对照组（pCONTROL组；n = 6）。记录长达8小时的心脏损伤、功能和血流动力学情况。小鼠（n = 52）经历4分钟心脏骤停后进行心肺复苏，随机分为两组，一组给予两剂2.4 mg/kg Bβ15 - 42（mFX06组；n = 26），另一组为对照组（mCONTROL组；n = 26）。评估14天存活率、神经认知功能和内皮完整性（对另外26只小鼠进行的额外实验）。
在猪中，Bβ15 - 42在8小时内减少了累积液体摄入量（3500 [2600 - 4200] vs 6800 [5700 - 7400] mL；p = 0.004）。在小鼠中，Bβ15 - 42提高了14天存活率（mFX06组与mCONTROL组相比；11/26 vs 6/26；p < 0.05），并在水迷宫试验中加快了神经认知恢复（能够完成试验的小鼠，15/26 vs 9/26；p < 0.05）。接受Bβ15 - 42治疗的小鼠肺内皮完整长度显著更长，肺白细胞浸润减少。
本研究证实了纤维蛋白衍生物在全身性缺血/再灌注损伤中起重要作用的新概念，纤维蛋白衍生肽Bβ15 - 42可减轻这种损伤。
