Background:Severe trauma is associated with systemic inflammation and organ dysfunction.Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating sever...Background:Severe trauma is associated with systemic inflammation and organ dysfunction.Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma.The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury.Methods:Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve controls.Weight,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p values<0.05(*).Results:Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(p<0.0001),lower hemoglobin(p<0.0001),and enlarged spleen to body weight ratios(p=0.004).Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naive(p<0.03,p<0.01).Plasma G-CSF was elevated in PT compared to both na?ve and LCHS(p<0.0001,p=0.02).LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema.Conclusions:Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe model.This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.展开更多
基金supported by the National Institutes of Healthsupported by NIH NIGMS R01 GM105893+2 种基金supported by postgraduate training grant NIH NIGMS T32 GM-008721 in burnstraumaand perioperative injury。
文摘Background:Severe trauma is associated with systemic inflammation and organ dysfunction.Preclinical rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human trauma.The aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic injury.Methods:Male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve controls.Weight,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p values<0.05(*).Results:Polytrauma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(p<0.0001),lower hemoglobin(p<0.0001),and enlarged spleen to body weight ratios(p=0.004).Both LCHS and PT demonstrated suppression of CFU-E and BFU-E growth compared to naive(p<0.03,p<0.01).Plasma G-CSF was elevated in PT compared to both na?ve and LCHS(p<0.0001,p=0.02).LCHS and PT demonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial edema.Conclusions:Multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe model.This may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.
