Resuscitation With Aged Blood Exacerbates Liver Injury in a Hemorrhagic Rat Model*

Matot, Idit; Katz, Miriam; Pappo, Orit; Zelig, Orly; Corchia, Nathalie; Yedgar, Shaul; Barshtein, Gregory; Bennett-Guerrero, E.; Abramovitch, Rinat

doi:10.1097/ccm.0b013e3182711b38

Cited by 37 publications

(42 citation statements)

References 36 publications

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“…It is thus logical to assess the effect of blood transfusion in the described rat model of PHx and bleeding. Indeed, this is the next step of our ongoing research, keeping in mind that previous studies from our lab showed blood transfusion to not always be beneficial to the liver (9, 10). Moreover, nowadays, restrictive blood-management protocols are endorsed, as reduced exposure to blood transfusions (with their inherent risks) results in improved patient safety and reduced costs (46).…”

Section: Discussionmentioning

confidence: 90%

Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy

et al. 2017

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Extensive liver resections are common, and bleeding is frequent in these operations. Impaired regeneration after partial hepatectomy (PHx) may contribute to liver failure. We thus assessed the impact of acute bleeding on the liver regeneration progress after PHx and explored possible contributing molecular mechanisms. In rats, the regeneration progress was delayed and attenuated with PHx and bleeding and was not restored with colloid resuscitation. Livers restored their initial volume by postoperative day (POD) 2 after PHx through hepatocyte proliferation vs. POD 4 in the PHx and bleeding group, primarily by hepatocyte hypertrophy. With bleeding, hepatocyte proliferation was hindered in two mechanisms: by inhibiting cells from starting proliferation and by causing hindrance in G1/S progression. Liver hypoxia was prominent, with significant prolonged up-regulation of hypoxia-inducible factors (HIF) and HIF-targeted genes only in the PHx and bleeding group. Gene expression profiling revealed alterations in numerous genes that belong to critical pathways, including cell cycle, DNA replication, PI3K-Akt, purine, and pyrimidine metabolism. Because liver surgery is frequently performed in patients with a predamaged liver, an improper regenerative process after PHx and bleeding might lead to decompensation. The results hint at specific pathways to target in order to improve liver regeneration during PHx and bleeding.—Matot, I., Nachmansson, N., Duev, O., Schulz, S., Schroeder-Stein, K., Frede, S., Abramovitch, R. Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy.

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Section: Discussionmentioning

confidence: 90%

Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy

et al. 2017

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“…3A) and by the percentage of UDC (fig. 3B) in the RBC population [5,18,31,32]. Figure 3A, depicting a representative ER curve, shows that cold storage induced an overall reduction in RBC deformability as shown by the shift of the St-RBC curve to lower ER values (elevation of the presence of low-deformable cells in the population) compared to F-RBC, and this was improved by rejuvenation.…”

Section: Resultsmentioning

confidence: 99%

“…In this method, applied to a maximum of less than 200 cells, the effects of surface area/volume ratios and of cytoplasmic viscosity on the overall RBC deformability are largely eliminated, causing the results to refer only to the membrane-specific changes that have occurred under cold storage and rejuvenation [40]. In our study, we measured the actual RBC deformability by direct visual monitoring of the changes in RBC shape under flow-induced shear stress, and the deformability parameters are derived from a large cell population (2,500 ± 300 cells), thereby enabling the derivation of parameters such as percentage of UDC, which better express St-RBC capacity to induced circulatory disorders [31,32]. …”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, RBC with ER E 1.1 are defined as ‘undeformable' cells (UDC), namely cells that do not deform under high shear stress (3.0 Pa). As shown and discussed in our previous studies, when considering the potential of reduced RBC deformability to induce microvascular occlusion, the portion of UDC is more clinically relevant than the shift in average values [30,31,32]. …”

Section: Methodsmentioning

confidence: 99%

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Storage-Induced Damage to Red Blood Cell Mechanical Properties Can Be Only Partially Reversed by Rejuvenation

Barshtein

Gural²,

Manny³

et al. 2014

Transfus Med Hemother

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Background: The storage of red blood cells (RBC) is associated with impairment of their properties that can induce a circulatory risk to recipients. In a preceding study (2009), we reported that post-storage rejuvenation (RJ) of stored RBC (St-RBC) efficiently reduced the storage-induced RBC/endothelial cell interaction, while only partially reversing the level of intracellular Ca²⁺, reactive oxygen species, and surface phosphatidylserine. In the present study, we examined the RJ effectiveness in repairing St-RBC mechanical properties. Methods: RBC, stored in CPDA-1 without pre-storage leukoreduction, were subjected to post-storage RJ, and the deformability, osmotic fragility (OF), and mechanical fragility (MF) of the rejuvenated St-RBC (St-RBC_Rj) were compared to those of untreated St-RBC and of freshly-collected RBC (F-RBC). Results: 5-week storage considerably increased OF and MF, and reduced the deformability of St-RBC. All alterations were only partially (40-70%) reversed by RJ, depending on the extent of the damage: the greater the damage, the lesser the relative effect of RJ. Conclusion: The findings of the present and preceding studies suggest that different St-RBC properties are differentially reversed by RJ, implying that some of the changes occur during storage and are irreversible.

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“…These prepared RBCs were transfused to rats of a different cohort after hemorrhage. This practice is common (23, 24). In addition, mixing blood from different rats very rarely induces cell aggregation (25).…”

Section: Methodsmentioning

confidence: 99%

Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment

Tan

Wang

et al. 2015

Critical Care Medicine

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Objectives Transfusing red blood cells (RBC) stored for longer than 14 days (old RBC) in humans is common. This transfusion can injure organs, such as lungs and kidneys. We determined whether transfusion with old RBC injured brain. Design Prospective, controlled, animal study Setting University research laboratory Subjects Adult male Sprague–Dawley rats Interventions Six-month old Sprague–Dawley rats lost 20% total blood volume and then received RBC prepared from equal volume of the lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage lesions similar to those of human RBC stored for 28 days). Some rats received intravenous cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion. Measurements and Main Results Rats were subjected to Barnes maze and fear conditioning tests from one week after blood transfusion. Rats transfused with old RBC but not fresh RBC took a longer time to identify the target hole in the Barnes maze and had less context-related fear conditioning behavior than control rats. Old RBC significantly increased interleukin 6 and ionized calcium-binding adapter molecule 1 in the hippocampus at 24 h after the transfusion. These effects were attenuated by sulforaphane and minocycline, an antibiotic with anti-inflammatory property. Old RBC solution had a higher concentration of cell-free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free hemoglobin. Rats received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats received old RBC. Conclusions These results provide initial evidence to suggest that transfusion of old RBC induces neuroinflammation and impairment of learning and memory. These effects may be mediated by cell-free hemoglobin.

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Resuscitation With Aged Blood Exacerbates Liver Injury in a Hemorrhagic Rat Model*

Abstract: Liver injury is exacerbated by the transfusion of stored blood, primarily due to the change in the rheological properties of RBC. This data call for clinical studies in patients undergoing liver resection or transplantation.

Cited by 37 publications

References 36 publications

Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy

Impaired liver regeneration after hepatectomy and bleeding is associated with a shift from hepatocyte proliferation to hypertrophy

Storage-Induced Damage to Red Blood Cell Mechanical Properties Can Be Only Partially Reversed by Rejuvenation

Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment

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