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Background: Resuscitation from hemorrhagic shock (HS) by blood transfusion restores oxygen (O2) delivery and provides hemodynamic stability. Current regulations allow red blood cells (RBCs) to be stored and used for up to 42 days. During storage, RBCs undergo many structural and functional changes. These storage lesions have been associated with adverse events and increased mortality after transfusion, increasing the need for improved RBC storage protocols. This study evaluates the efficacy of anaerobically stored RBCs to resuscitate rats from severe HS compared with conventionally stored RBCs., Methods and Results: Rat RBCs were stored under anaerobic, anaerobic/hypercapnic, or conventional conditions for a period of 3 weeks. Hemorrhage was induced by controlled bleeding, shock was maintained for 30 min, and RBCs were transfused to restore and maintain blood pressure near the prhemorrhage level. All storage conditions met current regulatory 24-h posttransfusion recovery requirements. Transfusion of anaerobically stored RBCs required significantly less RBC volume to restore and maintain hemodynamics. Anaerobic or anaerobic/hypercapnic RBCs restored hemodynamics better than conventionally stored RBCs. Resuscitation with conventionally stored RBCs impaired indices of left ventricular cardiac function, increased hypoxic tissue staining and inflammatory markers, and affected organ function compared with anaerobically stored RBCs., Conclusions: Resuscitation from HS via transfusion of anaerobically stored RBCs recovered cardiac function, restored hemodynamic stability, and improved outcomes.

In 2013, nearly 15 million units of banked blood were transfused in the United States of America alone. Blood shortages are expected to increase globally. Donated blood is not equal due to differences in quality and deterioration rate. There are no methods to detect time-dependent biochemical and biophysical changes of red blood cells (RBCs) or the deterioration rate of donated RBCs. Nine randomly selected RBC units collected by the San Diego Blood Bank were examined for interdonor variability over six weeks of storage. In vitro RBC quality was assessed weekly by conventional biochemical tests including free Hb, K+, ATP, P50, 2,3 DPG, lactate, and pH. Deformability was measured via cell filtration. Briefly, the RBC suspension (10% Hct), was forced through a 5.0-μm pore membrane (106 mm 2 ) at various flow rates. No interdonor variability in biochemical or mechanical parameters was observed at baseline. Interdonor variability in biochemical properties (free Hb, K+, ATP, P50, 2,3 DPG, lactate, and pH) was observed after 14 days of storage. However, significant differences from baseline in RBC mechanical properties (i.e., filterability) were observed as early as 7 days into storage at the lowest flow rates and after 28 days of storage at all flow rates. There was a net decrease in filterability over time for all donors, but the rate at which filterability decreased (i.e., deterioration rates) was different when comparing individual donors. Changes in all biochemical parameters were significant different between donors. These data suggest that filterability is more sensitive to changes in blood quality than conventional biochemical parameters.

Background: Small rodent models are routinely used to evaluate the safety and efficacy of blood transfusions. Limited comprehensive literature exists about effect of different storage solutions in rat red blood cells (RBCs) characteristics. RBCs undergo time dependent biochemical and biophysical changes during storage known as hypothermic storage lesions (HSLs)., Objective: This study evaluates the effects of RBC additive solutions (AS) during storage of rat RBCs., Methods: Blood was leukoreduced and stored as per manufacturer instructions at 4°C up to 42-days. Three solutions, CPDA-1; AS-1; and AS-7 (SOLX), were evaluated. Biochemical parameters measured included extracellular K+, pH, hemolysis, 2,3-diphosphoglycerate (2,3-DPG), oxygen affinity, ATP, and lactate. Mechanical properties measured included RBC deformability, elongation index (EI), RBC membrane shear elastic modulus (SEM), mean corpuscular volume (MCV), viscosity, and aggregability., Results: There were no differences in biochemical or mechanical parameters at baseline or after one week of storage. However, after two weeks, AS-7 preserved biochemical and mechanical properties as compared to CPDA-1 and AS-1. Changes were observed to be significant after 14-days of storage. AS-7 prevented extracellular K+ increase, reduced acidosis, showed lower hemolysis, preserved ATP and 2,3-DPG levels (consequently oxygen affinity), and reduced lactate. AS-7, when compared to CPDA-1 and AS-1, prevented the reduction in RBC deformability and was found to preserve the EI at multiple shear stresses, the membrane SEM, the aggregability and viscosity., Discussion: Rat RBCs stored with AS-7 presented reduced changes in biochemical and mechanical parameters, when compared with rat RBCs stored in CPDA-1 and AS-1, after as early as two weeks of storage.

BackgroundSmall rodent models are routinely used to evaluate the safety and efficacy of blood transfusions. Limited comprehensive literature exists about effect of different storage solutions in rat red blood cells (RBCs) characteristics. RBCs undergo time dependent biochemical and biophysical changes during storage known as hypothermic storage lesions (HSLs).ObjectiveThis study evaluates the effects of RBC additive solutions (AS) during storage of rat RBCs.MethodsBlood was leukoreduced and stored as per manufacturer instructions at 4°C up to 42-days. Three solutions, CPDA-1; AS-1; and AS-7 (SOLX), were evaluated. Biochemical parameters measured included extracellular K+, pH, hemolysis, 2,3-diphosphoglycerate (2,3-DPG), oxygen affinity, ATP, and lactate. Mechanical properties measured included RBC deformability, elongation index (EI), RBC membrane shear elastic modulus (SEM), mean corpuscular volume (MCV), viscosity, and aggregability.ResultsThere were no differences in biochemical or mechanical parameters at baseline or after one week of storage. However, after two weeks, AS-7 preserved biochemical and mechanical properties as compared to CPDA-1 and AS-1. Changes were observed to be significant after 14-days of storage. AS-7 prevented extracellular K+ increase, reduced acidosis, showed lower hemolysis, preserved ATP and 2,3-DPG levels (consequently oxygen affinity), and reduced lactate. AS-7, when compared to CPDA-1 and AS-1, prevented the reduction in RBC deformability and was found to preserve the EI at multiple shear stresses, the membrane SEM, the aggregability and viscosity.DiscussionRat RBCs stored with AS-7 presented reduced changes in biochemical and mechanical parameters, when compared with rat RBCs stored in CPDA-1 and AS-1, after as early as two weeks of storage.

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals’ systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc’s already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic. [ABSTRACT FROM AUTHOR]