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.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 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.Measurements and Main Results:
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.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 Bβ15–42.