Attenuating Ischemia and Reperfusion Injury with Polymerized Albumin

Ischemia-reperfusion increased vascular permeability, resulting in extravasation from the intravascular compartment into the tissue space. Fluid and small protein extravasation lead to increase interstitial fluid pressure and capillary collapse, impairing capillary exchange. Polymerized human serum albumin (PolyHSA) has an increased molecular weight (MW) compared to unpolymerized human serum albumin (HSA) and can improve intravascular fluid retention and improve recovery from ischemia-reperfusion injury. To test the hypothesis that polymerization of HSA can improve the recovery from ischemia-reperfusion, we study how exchanges transfusion of 20% of the blood volume with HSA or PolyHSA immediately before reperfusion can affect local ischemic tissue microhemodynamics, vascular integrity, and tissue viability in a hamster dorsal window chamber model. Microvascular flow and functional capillary density were maintained in animals exchanged with PolyHSA compared to HSA. Likewise, exchange transfusion with PolyHSA preserved vascular permeability measured with extravasation of fluorescently labeled dextran. The intravascular retention time of the exchange PolyHSA was significantly longer compared to the intravascular retention time of HAS. Lastly, the viability (apoptotic at 24 hours) tissue subjected to ischemia-reperfusion has increased viability in animals exchange with PolyHSA compared to HSA. Maintenance of microvascular perfusion, improvement in vascular integrity, and reduction in tissue damage resulting from reperfusion with PolyHSA suggest that PolyHSA can be a promising fluid therapy to improve outcomes of ischemia-reperfusion injury.