Protective Function of Endothelial Glycocalyx (EG) during Hemorrhagic Shock (HS) in Skeletal Muscle: Integration of Systemic and Local Parameters In Vivo

Successful resuscitation after HS requires tissue stabilization and restoration of microcirculatory function. EG shedding may be associated with endothelial and secondary injury, such as edema, inammation, and coagulation disturbances. This study examined fluid resuscitation effects on in vivo EG reconstitution, inflammation, coagulation function, arterial pressure (AP) and other traditional systemic parameters. Anesthetized rats (n=15) subjected to 1h of 40% HS were resuscitated with fresh frozen plasma (FFP) or normal saline (NS). EG thickness, blood flow, leukocyte rolling and adhesion, as well as permeability were studied on over 30 cremaster venules using intravital microscopy. HS reduced AP and EG thickness 54 ± 5 % and 40 ± 5 % respectively, compared to baseline (p<0.05). In NS‐treated rats, permeability was 50% higher while leukocyte rolling and adhesion increased 2‐fold compared to FFP treatment (p<0.05). Compared to baseline levels, both fluids improved systemic parameters and local blood flow, but only FFP significantly restored EG thickness (600 ± 40nm), plasma syndecan‐1 levels (5.9 ± 2.5μg/dl), clotting time (47 ± 2s), clot elasticity (707 ± 31dynes/cm 2 ), and reduced leukocyte adhesion as well as permeability. We concluded that recovery of EG may be essential to a better outcome after HS, since EG can be modulated by some resuscitation fluids and is associated with endothelial and microvascular functions. This integrated approach allows a better understanding of underlying injury mechanisms in vivo and the selection of more effective therapeutic strategies to HS. Supported by US Army Medical Research & Materiel Command.