Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis

Donald A Belcher,Andre F Palmer,Pedro Cabrales,Alexander T Williams

doi:10.1038/s41598-021-90431-z

Abstract

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

Highlights

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock
There were no other significant differences in heart rate (HR) and mean arterial blood pressure (MAP) compared to the baseline conditions in animals resuscitated with polymerized human serum albumin (PolyHSA) for the entirety of the protocol
From 6 h to the end of the protocol, animals resuscitated with PolyHSA had significantly (P < 0.05) greater MAP compared to animals that received human serum albumin (HSA) and those that had no fluid resuscitation

Summary

Introduction

Fluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Small colloidal proteins, such as human serum albumin (HSA), can extravasate from the vascular space into the tissue space, decreasing intravascular, and increasing extravascular colloidal osmotic pressure (COP), which promotes ultrafiltration and prevents reabsorption of fluid (Fig. 1b). Based on PolyHSA’s ability to maintain blood volume, restore blood viscosity, and hemodynamics, we hypothesize that fluid resuscitation with a PolyHSA solution would improve the maintenance of macro- and microcirculatory hemodynamics during a controlled septic shock model with systemic inflammation induced by LPS infusion. In addition to the LPS model, we investigated the effects of fluid resuscitation with PolyHSA in a hamster model of polymicrobial sepsis induced by cecal ligation and puncture (CLP)

Methods

Results

Discussion

Conclusion