PMID- 23040779 OWN - NLM STAT- MEDLINE DCOM- 20130801 LR - 20121008 IS - 1003-0603 (Print) IS - 1003-0603 (Linking) VI - 24 IP - 10 DP - 2012 Oct TI - [The effects of three dosages of nebulized unfractionated heparin on alveolar coagulation and tissue inflammation injury in endotoxin-induced acute lung injury rat model]. PG - 612-5 AB - OBJECTIVE: To observe the effects of three dosages of nebulized unfractionated heparin (UFH) on alveolar coagulation, inflammation and lung histology in endotoxin-induced acute lung injury rat model, and investigate the appropriated dose of local UFH in managing intrapulmonary coagulopathy. METHODS: Twenty-nine male Wistar rats were divided into control (n=5) and UFH group (n=24) in table of random number, which were duplicated to be endotoxin-induced ALI rat model with lipopolysaccharide (LPS) injecting by intravenous route. The UFH group was divided into three subgroups, which were administered once with 6, 12 and 18 U/g aerosolized UFH in 10 ml at 2 hours after challenge, respectively, while the control group was simply nebulized with normal saline. All rats were sacrificed at 6 hours after intravenous administration of LPS, bronchoalveolar lavage was performed, and the fluid was collected. Enzyme-linked immune sorbent assay (ELISA) was used to measure the level of thrombin-antithrombin complex (TATc), tumor necrosis factor-alpha (TNF-alpha) in bronchoalveolar lavage fluid (BALF), and lung wet/dry (W/D) weight ratio, histology score were recorded. RESULTS: At 6 hours after LPS-induced lung injury, the levels of TATc and TNF-alpha, lung W/D weight ratio and histology score in 6 U/g and 12 U/g group were all lower than those of control group significantly (TATc: 0.959+/-0.681 mug/L, 1.165+/-0.854 mug/L vs. 2.141+/-0.791 mug/L, TNF-alpha: 4.449+/-5.054 ng/L, 9.096+/-4.099 ng/L vs. 18.184+/-3.869 ng/L, W/D weight ratio: 7.018+/-1.137, 7.367+/-0.349 vs. 8.472+/-0.614, histology score: 16.0+/-1.0, 16.5+/-1.5 vs. 19.6+/-0.4, P<0.05 or P<0.01). There was no significant difference in the comparisons between the subgroups of UFH in TATc level in BALF and lung histology score. For the TNF-alphalevel in BALF, 18 U/g group evidently exceeded that of 6 U/g group (15.503+/-8.753 ng/L vs. 4.449+/-5.054 ng/L, P<0.01), and lung W/D weight ratio in 18 U/g group was also significantly higher comparing to 6 U/g (8.850+/-1.157 vs. 7.018+/-1.137, P<0.05) and 12 U/g group (8.850+/-1.157 vs. 7.367+/-0.349, P<0.05). CONCLUSION: It was appropriate for the dose of nebulized UFH to be administered no more than 12 U/g in ALI treatment, which was enough to inhibit alveolar coagulant cascade, decrease early inflammatory response and alleviate lung tissue injury. FAU - Wang, Zong-yu AU - Wang ZY AD - Department of Critical Care Medicine, Peking University, Beijing, China. FAU - Wu, Sheng-nan AU - Wu SN FAU - Zhu, Xi AU - Zhu X LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhongguo Wei Zhong Bing Ji Jiu Yi Xue JT - Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue JID - 9887521 RN - 0 (Endotoxins) RN - 9005-49-6 (Heparin) SB - IM MH - Acute Lung Injury/chemically induced/*drug therapy/*pathology MH - Administration, Inhalation MH - Animals MH - Blood Coagulation/drug effects MH - Endotoxins/adverse effects MH - Heparin/*administration & dosage/pharmacology MH - Inflammation/drug therapy MH - Lung/physiopathology MH - Male MH - Pulmonary Alveoli/drug effects MH - Rats MH - Rats, Wistar EDAT- 2012/10/09 06:00 MHDA- 2013/08/02 06:00 CRDT- 2012/10/09 06:00 PHST- 2012/10/09 06:00 [entrez] PHST- 2012/10/09 06:00 [pubmed] PHST- 2013/08/02 06:00 [medline] PST - ppublish SO - Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2012 Oct;24(10):612-5.