A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.

Abstract

Haemorrhagic shock causes ischaemia and subsequent fluid resuscitation causes reperfusion injury, jointly resulting in high morbidity and mortality. We tested whether the anti-inflammatory fibrin-derived peptide, Bbeta(15-42), also called FX06, is tissue protective in a model of haemorrhagic shock. In a pig model, we standardised the severity of haemorrhagic shock by achieving a cumulative oxygen deficit of approximately 100ml/kg body weight by withdrawing blood over a period of 1h. This was followed by resuscitation with shed blood and full electrolyte solution, and pigs were monitored for 3 days. At reperfusion, 17 pigs were randomly assigned to FX06 or solvent treatment. FX06-treated pigs demonstrated improved cardiac function (stroke volume index: 67ml/m(2) versus 33ml/m(2)), decreased troponin T release in the early reperfusion (0.24ng/ml versus 0.78ng/ml), decreased AST levels after 24h (106U/l versus 189U/l) and decreased creatinine levels after 24h (108micromol/l versus 159micromol/l). Furthermore, FX06-treated pigs demonstrated preservation of the gut/blood barrier, while controls demonstrated high endotoxin plasma levels indicating translocation of bacteria and/or its products (0.2EU/ml versus 24.3EU/ml) after 24h. This study also demonstrates a significantly improved neurological performance in the FX06 group as determined by S100beta serum levels (0.72microg/l versus 1.25microg/l) after 48h and neurological deficit scores (11 versus 70) after 24h. FX06 - when administered as an adjunct to fluid resuscitation therapy - is organ protective in pigs. Further investigations are warranted to reveal the protective mechanism of FX06.