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PubMed: 27308950

Title
The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide Homeostasis.
Journal
Anesthesia and analgesia
Volume
123
Issue
None
Pages
274-82
Date
2016-08-01
Authors
Barodka VM | Berkowitz DE | Frank SM | Goyal A | Johnson DJ | Lipsitz JA | Nagababu E | Scott AV

Evidence ef38f91fe6
JSON

In addition to cell-free Hb, membrane structural modification, externalization of phosphatidylserine,21 decreased cell membrane deformability,22,23 and increased endothelial adherence24 could alter vascular NO homeostasis.

a(CHEBI:"phosphatidyl-L-serine") decreases a(CHEBI:"nitric oxide") View Subject | View Object

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Endothelium, Vascular
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Introduction

bp(GO:"endothelial cell activation") decreases a(CHEBI:"nitric oxide") View Subject | View Object

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Endothelium, Vascular
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Introduction

p(HGNC:HBB) decreases a(CHEBI:"nitric oxide") View Subject | View Object

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Endothelium, Vascular
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Introduction

Evidence 454c0a5c10
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In vitro, direct exposure of vascular strips,38,39 brain tissue,40 polymorphoneutrophils, 41 and thoracic aorta42 to volatile anesthetic agents such as enflurane, isoflurane, and halothane has been shown to reversibly inhibit NOS activity.

a(CHEBI:enflurane) decreases a(MESH:"Nitric Oxide Synthase") View Subject | View Object

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Plasma
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a(CHEBI:halothane) decreases a(MESH:"Nitric Oxide Synthase") View Subject | View Object

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Plasma
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a(CHEBI:isoflurane) decreases a(MESH:"Nitric Oxide Synthase") View Subject | View Object

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Plasma
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Evidence eca56d7a61
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The stored RBCs had approximately 7 times the hemolysis of fresh blood.

a(HM:"stored erythrocytes") increases path(MESH:Hemolysis) View Subject | View Object

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Endothelium, Vascular
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Introduction

Evidence 207e7cb9f0
JSON

Any increase in hemolysis after transfusion of stored RBCs can be attributed to lysis of RBCs during storage or after transfusion (Figure 1B).

a(HM:"stored erythrocytes") increases path(MESH:Hemolysis) View Subject | View Object

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Plasma
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bp(MESH:"Blood Transfusion") increases path(MESH:Hemolysis) View Subject | View Object

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Plasma
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Evidence 7e1625627b
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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

a(HM:"stored erythrocytes") decreases a(MESH:Dilatation) View Subject | View Object

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Arteries
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Evidence 017a2cc8f0
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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.

a(HM:"stored erythrocytes") increases p(HGNC:HBB) View Subject | View Object

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Endothelium, Vascular
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Introduction

a(HM:"stored erythrocytes") decreases a(CHEBI:"nitric oxide") View Subject | View Object

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Endothelium, Vascular
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Introduction

Evidence c403d3a07e
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Third, during surgery, patients were intratracheally intubated, which prevented swallowing of saliva, which may have interrupted the nitrate-tonitrite pathway, thus contributing to the observed decrease in nitrite.

a(MESH:"Salivary Glands") increases rxn(reactants(a(CHEBI:nitrate)), products(a(CHEBI:nitrite))) View Subject | View Object

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Plasma
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Evidence 8729021873
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Studies have shown that nitrate concentrates in saliva and is reduced to nitrite by mouth commensal bacterial nitrate reductase and then nitrite is reduced to NO under acidic conditions of the stomach. 28,51,52

a(MESH:"Salivary Glands") increases rxn(reactants(a(CHEBI:nitrate)), products(a(CHEBI:nitrite))) View Subject | View Object

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Saliva
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Hypoxia
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Evidence 8d5e091881
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Several studies have shown that nitrite is reduced to NO by several heme proteins under hypoxic conditions, providing an eNOS-independent source of NO in the vasculature.28,47,48.

a(MESH:Hemeproteins) increases rxn(reactants(a(CHEBI:nitrite)), products(a(CHEBI:"nitric oxide"))) View Subject | View Object

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Plasma
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Hypoxia
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Evidence d90c50bea8
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Thus, we hypothesized that loss of blood during surgery and hemodilution from crystalloid administration might contribute to the observed decrease in plasma NOx levels.

a(MESH:Hemodilution) decreases a(CHEBI:nitrite) View Subject | View Object

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Plasma
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a(MESH:Hemodilution) decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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path(MESH:"Blood Loss, Surgical") decreases a(CHEBI:nitrite) View Subject | View Object

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Plasma
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path(MESH:"Blood Loss, Surgical") decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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Evidence 31e0b0167f
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Thus, it was apparent that blood loss and hemodilution from IV fluids rather than stored RBC transfusion likely played a role in the transient decrease of these NO metabolites.

a(MESH:Hemodilution) decreases a(CHEBI:nitrite) View Subject | View Object

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Plasma
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a(MESH:Hemodilution) decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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path(MESH:"Blood Loss, Surgical") decreases a(CHEBI:nitrite) View Subject | View Object

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Plasma
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path(MESH:"Blood Loss, Surgical") decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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Evidence 7f4dd7f801
JSON

The alternate explanation for a postoperative decrease in nitrate may be related to blood loss during and after surgery as well as hemodilution.

a(MESH:Hemodilution) decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
MeSH
Hypoxia
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Discussion

path(MESH:"Blood Loss, Surgical") decreases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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Hypoxia
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Evidence e47a71478a
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We calculated the loss of blood and extent of hemodilution during and after surgery based on the Hct levels for nontransfused patients (Table 1). Hct was significantly decreased (by approximately 20%, P = 0.0087) and hemodilution was significantly increased (P = 0.007) in these patients.

bp(MESH:"Blood Transfusion") increases bp(MESH:Hematocrit) View Subject | View Object

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Plasma
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bp(MESH:"Blood Transfusion") decreases a(MESH:Hemodilution) View Subject | View Object

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Plasma
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Evidence 5670b7434a
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An increase in plasma cell-free Hb and vascular dysfunction also has been shown after transfusion of autologous RBCs with long storage duration to healthy human subjects.19,20,37

bp(MESH:"Blood Transfusion") increases p(HGNC:HBB) View Subject | View Object

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Plasma
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bp(MESH:"Blood Transfusion") increases path(MESH:"Vascular System Injuries") View Subject | View Object

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Plasma
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Evidence a66f4c3949
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Several studies in animals have supported the idea that infusion of free Hb, stored RBC supernatant (preservation solution + plasma), and Hb-containing microvesicles causes vasoconstriction, vascular dysfunction, and vascular injury.12,16–18

p(HGNC:HBB) increases path(MESH:"Vascular System Injuries") View Subject | View Object

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Arteries
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Introduction

p(HGNC:HBB) increases bp(GO:vasoconstriction) View Subject | View Object

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Arteries
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Evidence 76753ef470
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Free Hb and Hb present in microvesicles oxidize vascular nitric oxide (NO) much faster than RBC-encapsulated Hb to form nitrate.14,15

p(HGNC:HBB) increases rxn(reactants(a(CHEBI:"nitric oxide")), products(a(CHEBI:nitrate))) View Subject | View Object

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Evidence 1b19745269
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Presence of any cell-free Hb limits NO diffusion from endothelium to smooth muscle cells for activation of guanylyl cyclase; as a consequence, mean arterial blood pressure increases.12,15

p(HGNC:HBB) increases bp(MESH:"Blood Pressure") View Subject | View Object

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Arteries
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Evidence 6579cb56e1
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The cell-free Hb in stored RBCs should actually increase nitrate by oxidizing NO to nitrate.

p(HGNC:HBB) increases a(CHEBI:nitrate) View Subject | View Object

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Plasma
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Hypoxia
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Discussion

Evidence e9283aaa62
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It is unlikely that loss of nitrite through surgically shed blood and hemodilution would produce a decrease of 50% from baseline because continuous synthesis of NO by eNOS should replenish the loss of nitrite.

p(HGNC:NOS3) increases a(CHEBI:"nitric oxide") View Subject | View Object

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Plasma
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Discussion

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