The Fibrin-Derived Peptide Bß15-42 (FX06) Ameliorates Vascular Leakage and Improves Survival and Neurocognitive Recovery: Implications From Two Animal Models of Cardiopulmonary Resuscitation.

ABSTRACT

OBJECTIVES: The fibrin-derived peptide Bß15-42 (FX06) has been proven to attenuate ischemia/reperfusion injury. We tested the hypothesis that Bß15-42 improves survival rate and neurocognitive recovery after cardiopulmonary resuscitation. DESIGN: Pig and mouse model of cardiopulmonary resuscitation. SETTING: Two university hospitals. SUBJECTS: Pigs and mice. INTERVENTIONS: Pigs (n = 16) were subjected to 8-minute cardiac arrest. Successful resuscitated pigs (n = 12) were randomized either to 3 mg/kg Bß15-42 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 Bß15-42 (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. MEASUREMENTS AND MAIN RESULTS: Bß15-42 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, Bß15-42 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). Bß15-42-treated mice showed a significant higher length of intact pulmonary endothelium and reduced pulmonary leukocyte infiltration. CONCLUSIONS: 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 Bß15-42.