a(HM:"stored erythrocytes")
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28 PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
We have also shown that older RBCs oxidize nitrite with faster rates compared to younger RBCs, which may account for decreased circulating nitrite levels in trauma patients receiving older RBCs14. PubMed:26202471
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
Pulmonary edema approximately doubled (Fig 1D), and lung bacterial CFUs significantly increased (Fig 1E) in mice resuscitated with stored RBCs compared to those that received fresh RBCs. PubMed:29522519
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
Figure 2G shows storage also resulted in a significant increase in Prx-2 oxidation. PubMed:26202471
The higher the basal (d7) level of Prx-2 oxidation, the higher the level of Prx-2 oxidation in the same RBC after 35 days of storage. PubMed:26202471
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
Fig 5A shows that extracellular serum levels of HMGB1 were approximately 5-fold higher in mice (n = 3) resuscitated with stored RBCs compared to mice resuscitated fresh RBCs. PubMed:29522519
Figure 1B presents these data and shows that (i) basal (time 0) Prx-2 oxidation was higher at day 35 relative to day 14 and 28 ( p < 0.05 by one-way analysis of variance (ANOVA) with Tukey post hoc test); (ii) H2O2 significantly increased Prx-2 oxidation, which was maximal at the first time point (5 min) measured; (iii) the magnitude of the maximal level of Prx-2 oxidation increased with RBC storage age ( p < 0.05 by one-way ANOVA with Tukey post hoc test for day 7 vs. 35 for 5 min data); and (iv) dimeric Prx-2 was slowly reduced back to the monomer over 60 min; however, this was not observed with day 35 RBC, where Prx- 2 remained > 75% oxidized. PubMed:25264713
Moreover, longer storage duration of red blood cells is associated with an increased risk of acute lung injury in patients with sepsis [63]. PubMed:29956069
Pulmonary edema approximately doubled (Fig 1D), and lung bacterial CFUs significantly increased (Fig 1E) in mice resuscitated with stored RBCs compared to those that received fresh RBCs. PubMed:29522519
TH and resuscitation with stored compared to fresh RBCs not only caused increased mortality but also significantly increased the severity of pulmonary edema induced by P. aeruginosa pneumonia (Fig 1D). PubMed:29522519
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
The postoperative infection rate was significantly higher in children receiving the oldest blood (third tertile, 25-38 days) compared to those receiving the freshest RBCs (first tertile, 7-15 days) (34% vs. 7%; p50.004). PubMed:29603246
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
Our findings using a mouse model of trauma and hemorrhagic shock with stored blood transfusion and subsequent PAK instillation demonstrate that transfusion with older stored RBCs increases the severity of bacterial pneumonia. PubMed:29522519
Furthermore, retrospective studies suggest an association between transfusion of older, stored RBCs and thrombosis (Spinella et al, 2009). PubMed:25307023
Figure 1B presents these data and shows that (i) basal (time 0) Prx-2 oxidation was higher at day 35 relative to day 14 and 28 ( p < 0.05 by one-way analysis of variance (ANOVA) with Tukey post hoc test); (ii) H2O2 significantly increased Prx-2 oxidation, which was maximal at the first time point (5 min) measured; (iii) the magnitude of the maximal level of Prx-2 oxidation increased with RBC storage age ( p < 0.05 by one-way ANOVA with Tukey post hoc test for day 7 vs. 35 for 5 min data); and (iv) dimeric Prx-2 was slowly reduced back to the monomer over 60 min; however, this was not observed with day 35 RBC, where Prx- 2 remained > 75% oxidized. PubMed:25264713
However, no differences in basal Trx-reductase activities, Trx protein levels, or NADPH levels were observed in day 7 versus 35 RBC (Fig. 2), suggesting that this was not the basis of differential Prx-2 reduction kinetics. PubMed:25264713
However, no differences in basal Trx-reductase activities, Trx protein levels, or NADPH levels were observed in day 7 versus 35 RBC (Fig. 2), suggesting that this was not the basis of differential Prx-2 reduction kinetics. PubMed:25264713
Furthermore, retrospective studies suggest an association between transfusion of older, stored RBCs and thrombosis (Spinella et al, 2009). PubMed:25307023
We have also shown that older RBCs oxidize nitrite with faster rates compared to younger RBCs, which may account for decreased circulating nitrite levels in trauma patients receiving older RBCs14. PubMed:26202471
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Figures 2A-F show changes in oxyhemoglobin, methemoglobin and free heme in both the intraerythrocytic and supernatant fractions in both d7 and d35 RBC. Significant storage-dependent increases for all species in the cell-free fraction were observed, with no storage-dependent differences observed in the erythrocyte. PubMed:26202471
More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28 PubMed:26202471
Consistent with our previous studies [25,36], free oxyHb, metHb, and heme levels were increased after 14 d of RBC storage, being 930 ± 125 μM, 40.3 ± 8.8 μM, and 168 ± 44.7 μM, respectively (mean ± SEM, n = 7). PubMed:29522519
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
Figure 2G shows storage also resulted in a significant increase in Prx-2 oxidation. PubMed:26202471
The higher the basal (d7) level of Prx-2 oxidation, the higher the level of Prx-2 oxidation in the same RBC after 35 days of storage. PubMed:26202471
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
The stored RBCs had approximately 7 times the hemolysis of fresh blood. PubMed:27308950
Any increase in hemolysis after transfusion of stored RBCs can be attributed to lysis of RBCs during storage or after transfusion (Figure 1B). PubMed:27308950
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471
In humans, infusion of RBCs stored for longer durations has been shown to significantly reduce brachial artery flow-mediated dilation12 and acetylcholine-stimulated forearm blood flow compared with fresher blood.19,20 PubMed:27308950
In the current observational study in patients undergoing multilevel spinal fusion surgery, we tested the hypothesis that moderate doses of stored RBC transfusions increase intravascular cell-free Hb and decrease NO availability in surgical patients. PubMed:27308950
In the current observational study in patients undergoing multilevel spinal fusion surgery, we tested the hypothesis that moderate doses of stored RBC transfusions increase intravascular cell-free Hb and decrease NO availability in surgical patients. PubMed:27308950
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
Stored RBCs exhibit altered biophysical characteristics, including higher cell rigidity that accounts in part for impaired blood flow hemodynamics and adverse effects of RBC transfusion [26]. PubMed:28458720
For example, Hb and subsequently, hemin accumulate during storage of human blood as RBC membrane integrity decreases [4]. PubMed:30281034
Stored RBCs exhibit altered biophysical characteristics, including higher cell rigidity that accounts in part for impaired blood flow hemodynamics and adverse effects of RBC transfusion [26]. PubMed:28458720
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
Stored RBCs undergo a complex structural and metabolic impairment that includes leakage of hemoglobin from the cells and hemolysis, reduced energy and NO production, formation of toxic products, such as lysophospholipids and free iron, phosphatidylserine exposure and shedding MPs [59]. PubMed:28458720
However, mortality significantly increased in mice resuscitated with stored RBCs (median survival 8 h, n = 9), with all mice dying within 20 h of PAK instillation (Fig 1C). PubMed:29522519
Pulmonary edema approximately doubled (Fig 1D), and lung bacterial CFUs significantly increased (Fig 1E) in mice resuscitated with stored RBCs compared to those that received fresh RBCs. PubMed:29522519
TH and resuscitation with stored compared to fresh RBCs not only caused increased mortality but also significantly increased the severity of pulmonary edema induced by P. aeruginosa pneumonia (Fig 1D). PubMed:29522519
Pulmonary edema approximately doubled (Fig 1D), and lung bacterial CFUs significantly increased (Fig 1E) in mice resuscitated with stored RBCs compared to those that received fresh RBCs. PubMed:29522519
Fig 2 shows that free hemoglobin and free heme were higher 4 h after resuscitation with stored RBCs compared to fresh RBCs (n = 3±7 as indicated); NTBI level was also higher, but this difference did not reach statistical significance (p = 0.07). PubMed:29522519
Fig 5A shows that extracellular serum levels of HMGB1 were approximately 5-fold higher in mice (n = 3) resuscitated with stored RBCs compared to mice resuscitated fresh RBCs. PubMed:29522519
Our findings using a mouse model of trauma and hemorrhagic shock with stored blood transfusion and subsequent PAK instillation demonstrate that transfusion with older stored RBCs increases the severity of bacterial pneumonia. PubMed:29522519
The postoperative infection rate was significantly higher in children receiving the oldest blood (third tertile, 25-38 days) compared to those receiving the freshest RBCs (first tertile, 7-15 days) (34% vs. 7%; p50.004). PubMed:29603246
Moreover, longer storage duration of red blood cells is associated with an increased risk of acute lung injury in patients with sepsis [63]. PubMed:29956069
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.