DRAG-REDUCING HYALURONIC ACID INCREASES SURVIVAL IN PROFOUNDLY HEMORRHAGED RATS

Abstract

We tested the hypothesis that the infusion of a small volume of a drag-reducing polymer (DRP) solution can prolong survival in rats subjected to lethal hemorrhagic shock (HS; shed 51% of estimated blood volume) in the absence of complete resuscitation with fluids or blood. In this set of experiments, we used a newly designed mixture of hyaluronic acid (molecular weight, approximately 2.0 x 10 d; 0.4 mg/mL) and polyethylene oxide (molecular weight, approximately 4 x 10 d; 0.05 mg/mL) dissolved in sterile phosphate-buffered saline. Anesthetized rats were subjected to a volume-controlled HS. During the first 20 min, blood (21.7 mL/kg) was withdrawn. During the next 40 min, additional blood (14 mL/kg) was withdrawn, and during the final 20 min, saline vehicle or saline + DRP (2.8 mL/kg) was simultaneously infused. The survival rate of the rats treated with the hyaluronic acid/polyethylene oxide was significantly higher (P < 0.01). The mean survival times for control and DRP-treated animals were 100.4 +/- 9.5 vs. 154.8 +/- 7.0 min (P < 0.001). MAP was higher (P < 0.005) and skin perfusion was significantly improved in the DRP-treated group after the end of the DRP infusion. These results support the use of nanomolar concentrations of DRP to prolong survival in rats after lethal HS in the absence of fluid resuscitation. The DRP formulation studied here warrants further evaluation for the amelioration of critical illness associated with profound shock when access to resuscitation fluids may not be possible or delayed.