From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ∼85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb-deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO 2 , but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO 2 were corrected by SNO-Hb-repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O 2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients.ethyl nitrite | hemoglobin cysbeta93 | nitric oxide | storage lesion

Banked blood exhibits impairments in nitric oxide (NO)‐based oxygen delivery capability, reflected in rapid depletion of S‐nitrosohemoglobin (SNO‐Hb). We hypothesized that transfusion of even freshly‐stored blood used in pediatric heart surgery would reduce SNO‐Hb levels and worsen outcome. In a retrospective review (n = 29), the percent of estimated blood volume (% eBV) replaced by transfusion directly correlated with ventilator time and inversely correlated with kidney function; similar results were obtained in a prospective arm (n = 20). In addition, an inverse association was identified between SNO‐Hb and postoperative increase in Hb (∆Hb), reflecting the amount of blood retained by the patient. Both SNO‐Hb and ∆Hb correlated with the probability of kidney dysfunction and oxygenation‐related complications. Further, regression analysis identified SNO‐Hb as an inverse predictor of outcome. The findings suggest that SNO‐Hb and ∆Hb are prognostic biomarkers following pediatric cardiopulmonary bypass, and that maintenance of red blood cell‐derived NO bioactivity might confer therapeutic benefit.

Probe microscopes are key tools for surface characterization and nanoscale science. This category of instrumentation has enabled researchers both to investigate properties and to manipulate materials at the nanoscale. When introduced to nanoscale science and engineering, students frequently ask "How do we know it is there if we can't see it with our eyes?" To address this query, students of all ages can be introduced to the basic concepts of probe microscopy and given the opportunity to explore probe techniques. We have developed interactive exhibits and classroom activities that allow middle-and high-school students to detect and map topography, stiffness, and magnetic field. These products will be presented along with assessment data collected with the Rennie and McClafferty protocol for formative evaluation of interactive exhibits.

No abstract