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Accession Number:

AD1122898

Title:

Novel Artificial Erythrocyte for In-Field Resuscitation of Hemorrhagic Shock

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Report Date:

2019-10-01

Abstract:

The first ErythroMer prototype (EM-V1) was structurally stable, toroidal (size: 17510nm; pdi: 0.260.0 by DLS, confirmed by TEM and AFM). CH50 (complement activation) results were indistinguishable from negative controls, and we observed no impact on plasma viscosity(1:10 and 1:5 dilution) with EM-V1. For the most recent variant of EM-V1 with increased concentration of the allosteric effector, p50 was33.33 Torr (control RBC p50: 24.76). EM NO sequestration varied with shell crosslinking and was RBCs. Important to the future successful testing of EM in various models of prolonged-field care (PFC), we developed and fine-tuned a rabbit hemorrhagic shock model. Initial shock studies in a rodent model: 40 blood volume was removed; animals were resuscitated with EM-V1 (40wt/vol , [Hb]=4mM) or normal saline (N=6, each). EM stabilized hemodynamics and following parameters within 1h: lactic acidosis (8.22.1 v 3.21.5 mM) [for EM and NS, respectively, throughout]; A-VO2 difference (2411 v 6723 ) and brain pO2 (30.51.4 v 17.21.3Torr); p<0.05, for all. Hemodilution model: HIF-1(ODD)luciferase mice underwent hemodilution (70 v/v) with pentastarch, blood/autotransfusion, or EM [N=6, all; native Hb target nadir 5 mg/dL). HIF-luc radiance was higher with HES than autotransfusion and EM, which did not differ (p<0.01). We recently transitioned to our second prototype, EM-V2, and have preliminarily structural data (size: 320nm; pdi: 0.37 by DLS). We will endeavor to mirror the recent p50 results from our first prototype in Y2 of this grant with EM-V2. Early PK testing with EM-V2 revealed distributiont1/2=4.5hrs in rabbits (n=2). In rabbit oxygenation/acute shock studies, sufficient blood volume (BV) was removed to induce an increase in lactate, decrease in liver pO2 and decrease in mean arterial pressure; animals were resuscitated with EM (~30 BV, N=3) or 5 Albumin or Auto-transfusion (N=5) of whole blood (N=6)

Pages:

18

File Size:

1.41MB

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Distribution Statement:

Approved For Public Release

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