Recombinant Bcl-xL attenuates vascular hyperpermeability in a rat model of hemorrhagic shock

Following hemorrhagic shock (HS), vascular hyperpermeability, that is, the leakage of fluid, nutrients and proteins into the extravascular space occurs primarily due to the disruption of the endothelial cell–cell adherens junctional complex. Studies from our laboratory demonstrate that activation of the mitochondria-mediated ‘intrinsic’ apoptotic signaling cascade has a significant role in modulating HS-induced hyperpermeability. Here we report the novel use of recombinant Bcl-xL, an anti-apoptotic protein, to control HS-induced vascular hyperpermeability. Our results corroborate involvement of vascular hyperpermeability and apoptotic signaling. HS (the mean arterial pressure (MAP) was reduced to 40 mm Hg for 60 min followed by resuscitation to 90 mm Hg for 60 min) in rats resulted in vascular hyperpermeability as determined by intravital microscopy. Treatment of Bcl-xL (2.5 µ g/ml of rat blood in non-lipid cationic polymer, i.v.) before, during and even after HS attenuated or reversed HS-induced vascular hyperpermeability significantly ( P