RGD Reference Report - Activated platelets in heparinized shed blood: the "second hit" of acute lung injury in trauma/hemorrhagic shock models. - Rat Genome Database

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Activated platelets in heparinized shed blood: the "second hit" of acute lung injury in trauma/hemorrhagic shock models.

Authors: Harr, JN  Moore, EE  Wohlauer, MV  Fragoso, M  Gamboni, F  Liang, X  Banerjee, A  Silliman, CC 
Citation: Harr JN, etal., Shock. 2011 Dec;36(6):595-603.
RGD ID: 6480522
Pubmed: PMID:21841533   (View Abstract at PubMed)
PMCID: PMC3220733   (View Article at PubMed Central)
DOI: DOI:10.1097/SHK.0b013e318231ee76   (Journal Full-text)

The return of heparinized shed blood (SB) in trauma/hemorrhagic shock (T/HS) models remains controversial because of potential anti-inflammatory properties. Although ubiquitous as an anticoagulant, heparin is ineffective on cellular coagulation as an antithrombotic agent. Therefore, we hypothesized that returning heparinized SB would paradoxically enhance acute lung injury (ALI) after T/HS because of the infusion of activated platelets. Sprague-Dawley rats, anesthetized with pentobarbital, underwent laparotomy and hemorrhage-induced shock (MAP of 30 mmHg x 45 min). Animals were resuscitated with a combination of normal saline and returned SB. Shed blood was collected in either 80 U/kg of heparin, 800 U/kg of heparin, or citrate or diluted 1:8 with normal saline. An additional group of animals were pretreated with a platelet P2Y12 receptor antagonist (clopidogrel) before T/HS. Bronchoalveolar lavage, lung myeloperoxidase assays, pulmonary immunofluorescence, and blood smears were conducted. Bronchoalveolar lavage protein increased in animals resuscitated with heparinized SB (T/HS + 80 U/kg Hep 1.62 +/- 0.29, T/HS + 800 U/kg Hep 1.30 +/- 0.15 vs. T/SS 0.51 +/- 0.16 and T/HS Citrate 0.7 +/- 0.09) (P < 0.0001). Blood smears and platelet function assays revealed platelet aggregates and increased platelet activation. Animals pretreated with a platelet P2Y12 receptor antagonist were protected from postinjury ALI (P < 0.0001). Animals with return of SB had increased pulmonary polymorphonuclear leukocyte sequestration (P < 0.0001). Pulmonary immunofluorescence demonstrated microthrombi only in the T/HS group receiving heparinized SB (P < 0.0001). The return of heparinized SB functions as a "second hit" to enhance ALI, with activated platelets propagating microthrombi and pulmonary polymorphonuclear leukocyte recruitment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Lung Injury  ISOP2ry12 (Rattus norvegicus)6480522; 6480522associated with Shock and HemorrhagicRGD 
Acute Lung Injury  IMP 6480522associated with Shock and HemorrhagicRGD 

Objects Annotated

Genes (Rattus norvegicus)
P2ry12  (purinergic receptor P2Y12)

Genes (Mus musculus)
P2ry12  (purinergic receptor P2Y, G-protein coupled 12)

Genes (Homo sapiens)
P2RY12  (purinergic receptor P2Y12)


Additional Information