The Fibrin-Derived Peptide Bβ15-42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation.
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.
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.
Stefan
S
Bergt
Matthias
M
Gruenewald
Claudia
C
Beltschany
Andrea
A
Grub
Tobias
T
Neumann
Martin
M
Albrecht
Brigitte
B
Vollmar
Kai
K
Zacharowski
Jan P
JP
Roesner
Patrick
P
Meybohm
D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D006323:Heart Arrest / Q000188:drug therapy / Q000628:therapy*; D006334:Heart Function Tests; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control*; D016019:Survival Analysis; D013552:Swine
D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42)