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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

ABSTRACT: Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for 1h. Volume restitution was performed by infusion of the equivalent of 2.5 units of packed cells, and the animals were followed for 90 min. Resuscitation study groups were non-oxygen functional fresh RBCs where the hemoglobin (Hb) was converted to methemoglobin (MetHb) [MetRBC], fully oxygen functional fresh RBCs [OxyRBC] and 10% hydroxyethyl starch [HES] as a volume control solution. Measurement of systemic variables, microvascular hemodynamics and capillary perfusion were performed during the hemorrhage, hypovolemic shock and resuscitation. Final blood viscosities after the entire protocol were 3.8 cP for transfusion of RBCs and 2.9 cP for resuscitation with HES (baseline: 4.2 cP). Volume restitution with RBCs with or without oxygen carrying capacity recovered higher mean arterial pressure (MAP) than HES. Functional capillary density (FCD) was substantially higher for transfusion versus HES, and the presence of MetHb in the fresh RBC did not change FCD or microvascular hemodynamics. Oxygen delivery and extraction were significantly lower for resuscitation with HES and MetRBC compared to OxyRBC. Incomplete re-establishment of perfusion after resuscitation with HES could also be a consequence of the inappropriate restoration of blood rheological properties which unbalance compensatory mechanisms, and appear to be independent of the reduction in oxygen carrying capacity.

SUBMITTER: Cabrales P

PROVIDER: S-EPMC3224809 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

Cabrales Pedro P Intaglietta Marcos M Tsai Amy G AG

Resuscitation 20070503 1

Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for 1h. Volume restitution was performed by infusion of th ...[more]

PMID: 17481796

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Project description:Background: Centhaquine (CQ) (Lyfaquin®) is in late stage clinical development as a safe and effective first-in-class resuscitative agent for hemorrhagic shock patients (NCT02408731, NCT04056065, and NCT04045327). Acute kidney injury (AKI) is known to be associated with hemorrhagic shock. Hence, effect of CQ on protection of kidneys from damage due to hemorrhagic shock was investigated. Methods: To assess effect of CQ on AKI in shock, we created a rat model with hemorrhagic shock and AKI. Renal arteries were clamped and de-clamped to induce AKI like ischemia/reperfusion model and hemorrhage was carried out by withdrawing blood for 30 min. Rats were resuscitated with CQ (0.02 mg/kg) for 10 min. MAP, heart rate (HR), and renal blood flow (RBF) were monitored for 120 min. Results: CQ produced a significant improvement in RBF compared to vehicle (p< 0.003) even though MAP and HR was similar in CQ and vehicle groups. Blood lactate level was lower (p = 0.0064) in CQ than vehicle at 120 min post-resuscitation. Histopathological analysis of tissues indicated greater renal damage in vehicle than CQ. Western blots showed higher HIF-1α (p = 0.0152) and lower NGAL (p = 0.01626) levels in CQ vs vehicle. Immunofluorescence in the kidney cortex and medulla showed significantly higher (p< 0.045) expression of HIF-1α and lower expression of Bax (p< 0.044) in CQ. Expression of PHD 3 (p< 0.0001) was higher, while the expression of Cytochrome C (p = 0.01429) was lower in the cortex of CQ than vehicle. Conclusion: Results show CQ (Lyfaquin®) increased renal blood flow, augmented hypoxia response, decreased tissue damage and apoptosis following hemorrhagic shock induced AKI, and may be explored to prevent/treat AKI. Translational Statement: Centhaquine (CQ) is safe for human use and currently in late stage clinical development as a first-in-class resuscitative agent to treat hemorrhagic shock. In the current study, we have explored a novel role of CQ in protection from hemorrhagic shock induced AKI, indicating its potential to treat/prevent AKI.

Project description:OBJECTIVES:To present the recommendations and supporting literature for RBC transfusions in critically ill children with bleeding developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN:Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children. METHODS:The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The bleeding subgroup included five experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS:Transfusion and Anemia Expertise Initiative Consensus Conference experts developed a total of six recommendations focused on transfusion in the critically ill child with acute bleeding. In critically ill children with nonlife-threatening bleeding, we recommend giving a RBC transfusion for a hemoglobin concentration less than 5?g/dL, and be considered for a hemoglobin concentration between 5 and 7?g/dL. In critically ill children with hemorrhagic shock, we suggest that RBCs, plasma and platelets transfusion ratio between 2:1:1 to 1:1:1 until the bleeding is no longer life-threatening. We recommend future studies to develop physiologic and laboratory measures to indicate the need for RBC transfusions, and to determine if goal directed hemostatic resuscitation improves survival. Finally, we recommend future studies to determine if low titer group O whole blood is more efficacious and safe compared with reconstituted whole blood in children with hemorrhagic shock. CONCLUSIONS:The Transfusion and Anemia Expertise Initiative Consensus Conference developed pediatric specific recommendations regarding RBC transfusion management in the critically ill child with acute bleeding, as well as recommendations to help guide future research priorities.

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

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Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity.

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