Transfusion of Anaerobically or Conventionally Stored Blood After Hemorrhagic Shock

Abstract

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.

Hypoxic storage of red blood cells improves metabolism and post‐transfusion recovery

“…In prior work on rodent models of shock, limited improvements in PTR (approx. 3%) did not mirror a remarkably superior performance of hypoxic RBCs in resuscitating hemorrhaged rats . Units donated by the same donors (as is the case in the present study) tend not to show consistent reproducible levels of spontaneous hemolysis across multiple donations .…”

“…In the past 10 years, we have provided compelling evidence that hypoxic storage of RBCs ameliorates the storage lesion through a series of compounding mechanisms, including 1) the concomitant removal of carbon dioxide during the process of deoxygenation, which results in the intracellular alkalinization of the unit, and in turn favors the activation of glycolysis, the Rapoport‐Luebering shunt and the activity of glucose 6‐phosphate dehydrogenase; 2) improved preservation of DPG and redox metabolism, both by constraining reactive oxygen species–generating reactions and promoting adenosine triphosphate (ATP)‐dependent glutathione synthesis; 3) preventing oxidation of functional and structural proteins, including hemoglobin, band 3, peroxiredoxin 2, and glyceraldehyde 3‐phosphate dehydrogenase; and 4) improved end‐of‐storage morphology and decreased vesiculation . In the light of this evidence, we recently showed in a rodent model of trauma and hemorrhage that transfusion of end‐of‐storage hypoxic RBCs was superior to transfusion of conventional blood in correcting systemic hypoxia and preventing organ damage at a fraction of the transfused volume . Despite this encouraging evidence, until now only preliminary studies have been performed in humans to demonstrate the safety and efficacy of hypoxic blood transfusion.…”

ZOOMICS: Comparative Metabolomics of Red Blood Cells From Old World Monkeys and Humans

“…Animal models have contributed significantly to the fields of hematology and transfusion medicine. Rodent [e.g., mice (Howie et al, 2019), rats (Williams et al, 2019), guinea pigs (Baek et al, 2017)], canine (Klein, 2017), and swine (Clendenen et al, 2017) models have been extensively adopted in blood research for years. However, being genotypically closest to humans, non-human primate (NHP) biology is most phenotypically comparable to human biology.…”

Balance between oxygen transport and blood rheology during resuscitation from hemorrhagic shock with polymerized bovine hemoglobin

“…Parallel LV volume was calibrated via intravenous injection of 40 L of 15% (wt/vol) NaCl (23). Indexes of cardiac function and O 2 delivery were calculated as previously described (33).…”