Activated platelets in heparinized shed blood: the "second hit" of acute lung injury in trauma/hemorrhagic shock models. Shock 2011 Dec;36(6):595-603
Date
08/16/2011Pubmed ID
21841533Pubmed Central ID
PMC3220733DOI
10.1097/SHK.0b013e318231ee76Scopus ID
2-s2.0-81755172003 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
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 × 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.
Author List
Harr JN, Moore EE, Wohlauer MV, Fragoso M, Gamboni F, Liang X, Banerjee A, Silliman CCMESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAnimals
Blood Platelets
Blood Transfusion, Autologous
Male
Platelet Activation
Rats
Rats, Sprague-Dawley
Shock, Hemorrhagic
Wounds and Injuries
