Inhaled nitric oxide attenuates the adverse effects of transfusing stored red blood cells in mice with endothelial dysfunction after hemorrhagic shock

Abstract

BackgroundTransfusion of red blood cells (RBCs) stored for prolonged periods is associated in some retrospective studies with adverse clinic outcomes in patients. We investigated whether transfusion with stored RBCs would increase tissue injury, inflammation, oxidative stress and mortality (adverse effects of transfusing stored RBCs) in a murine model of hemorrhagic shock. We tested whether the adverse effects associated with transfusing stored RBCs were exacerbated by endothelial dysfunction and ameliorated by inhaling nitric oxide.MethodsWe studied mice fed a high‐fat diet (HFD‐fed, to induce endothelial dysfunction) or a standard diet for 4–6 weeks. Mice were subjected to 90 min of hemorrhagic shock, followed by resuscitation with leukoreduced syngeneic RBCs stored for less than 24 h (fresh RBCs) or stored for 2 weeks (stored RBCs).ResultsIn standard diet‐fed mice at 2 h after resuscitation, transfusion with stored RBCs increased tissue injury more than transfusion with fresh RBCs. The adverse effects of transfusing stored RBCs were more marked in HFD‐fed mice and associated with increased lactate levels and short‐term mortality. Compared with fresh RBCs, resuscitation with stored RBCs was associated with a reduction in P50, increased plasma hemoglobin levels, and increased indices of inflammation and oxidative stress, effects that were exacerbated in HFD‐fed mice. Inhaled nitric oxide reduced tissue injury, lactate levels, and indices of inflammation and oxidative stress, as well as improved short‐term survival in HFD‐fed mice resuscitated with stored RBCs.ConclusionsResuscitation with stored RBCs adversely impacts outcome in mice with hemorrhagic shock, an effect which is exacerbated in mice with endothelial dysfunction. Inhaled nitric oxide reduces tissue injury and improves short‐term survival in HFD‐fed mice resuscitated with stored RBCs.