Intratracheal heparin improves plastic bronchitis due to sulfur mustard analog.

Intratracheal heparin improves plastic bronchitis due to sulfur mustard analog.
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DOI:
10.1002/ppul.23043
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发表时间:
2015-02
影响因子:
3.1
通讯作者:
White, Carl W.
White, Carl W.
中科院分区:
医学3区
文献类型:
--
作者:
Houin, Paul R.;Veress, Livia A.;Rancourt, Raymond C.;Hendry-Hofer, Tara B.;Loader, Joan E.;Rioux, Jacqueline S.;Garlick, Rhonda B.;White, Carl W.

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吸入硫芥(SM)和硫芥类似物2-氯乙基乙基硫醚(CEES),会导致纤维性铸型形成,阻塞传导气道,类似于Fontan生理性诱发的塑性支气管炎儿童。这些气道铸型引起严重的死亡率和发病率,包括低氧血症和呼吸窘迫。我们的假设是,气管内肝素是一种成本效益高且易于保存的抢救治疗,可以逆转支气管铸型形成引起的发病率和死亡率。Sprague-Dawley大鼠仅通过鼻腔吸入气溶胶暴露于7.5%的CEES,造成广泛的铸造和死亡。将大鼠分为三组:未处理组、磷酸盐缓冲盐水(PBS)组和肝素组。通过血氧饱和度和临床窘迫来评估发病率。取血和支气管肺泡灌洗液(BALF)进行分析,固定肺进行气道显微解剖,量化气道铸型形成程度。与未治疗组(75%)和pbs治疗组(90%)相比,气管内给予肝素可提高生存率(100%)。肝素治疗大鼠的血氧饱和度、临床窘迫和气道铸型评分也有所改善。肝素治疗的大鼠凝血酶凝血次数增加,Xa因子抑制和部分凝血活素激活次数增加,表明肝素的全身吸收。与pbs治疗的对照大鼠相比,2/6肝素治疗大鼠的BALF中红细胞(rbc)也有所增加。吸入CEES后1小时气管内注射肝素可改善生存、氧合、气道阻塞和临床窘迫。肝素在经气管内处理的大鼠中有全身吸收。一些大鼠BALF中红细胞增多,提示吸入SM后长期使用可能导致肺内出血。
Inhalation of sulfur mustard (SM) and SM analog, 2-chloroethyl ethyl sulfide (CEES), cause fibrinous cast formation that occludes the conducting airways, similar to children with Fontan physiology-induced plastic bronchitis. These airway casts cause significant mortality and morbidity, including hypoxemia and respiratory distress. Our hypothesis was that intratracheal heparin, a highly cost effective and easily preserved rescue therapy, could reverse morbidity and mortality induced by bronchial cast formation. Sprague-Dawley rats were exposed to 7.5% CEES via nose-only aerosol inhalation to produce extensive cast formation and mortality. The rats were distributed into three groups: non-treated, phosphate-buffered saline (PBS)-treated, and heparin-treated groups. Morbidity was assessed with oxygen saturations and clinical distress. Blood and bronchoalveolar lavage fluid (BALF) were obtained for analysis, and lungs were fixed for airway microdissection to quantify the extent of airway cast formation. Heparin, given intratracheally improved survival (100%) when compared to non-treated (75%) and PBS-treated (90%) controls. Heparin-treated rats also had improved oxygen saturations, clinical distress and airway cast scores. Heparin-treated rats had increased thrombin clotting times, factor Xa inhibition and activated partial thromboplastin times, indicating systemic absorption of heparin. There were also increased red blood cells (RBCs) in the BALF in 2/6 heparin-treated rats compared to PBS-treated control rats. Intratracheal heparin 1 hr after CEES inhalation improved survival, oxygenation, airway obstruction, and clinical distress. There was systemic absorption of heparin in rats treated intratracheally. Some rats had increased RBCs in BALF, suggesting a potential for intrapulmonary bleeding if used chronically after SM inhalation.
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