Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model.
Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model.
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DOI：
10.1002/lio2.1093
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发表时间：
2023-08
影响因子：
1.9
通讯作者：
Dion, Gregory R. R.
中科院分区：
文献类型：
--
作者：
Malka, Ronit;Gonzales, Gabriela;Detar, Will;Marinelli, Lisa;Lee, Christine M. M.;Isaac, Alisa;Miar, Solaleh;Cook, Stacy;Guda, Teja;Dion, Gregory R. R.
吸入性烧伤经常导致发声困难和气道狭窄。我们假设通过新型药物洗脱电纺聚合物网状气管导管（ETT）局部地塞米松递送可减少吸入烧伤时声带的生物力学和组织学变化。将载有地塞米松的聚合物网电纺到修剪成经声门喉内段的 ETT 上，并固定在 9 只约克郡杂交猪身上，并进行 150°C 直接吸入烧伤。未涂层的 ETT 被植入另外 9 只具有相同烧伤情况的猪体内。 ETT 片段维持 3 天和 7 天。使用自动压痕图测量声带（VF）结构刚度，并在各组之间进行比较并与四个未受伤的对照组进行比较，并进行匹配的组织学评估。使用双向方差分析、Tukey 事后检验和 Wilcoxon 秩和检验进行统计分析。烧伤后心室颤动硬度随着插管时间的延长而降低，从 3 天时的 19.4 (7.6) mN/mm 降至 7 天时的 11.3 (5.2) mN/mm (p < .0001)。局部使用地塞米松后，硬度也同样降低，从第 3 天的 25.9 (17.2) mN/mm 降至第 7 天的 18.1 (13.0) mN/mm (p< .0001)。与没有局部地塞米松的组织相比，地塞米松组的 VF 硬度增加 (p = .0002)，并且所有放置 ETT 的组在第 3 天时组织硬度更高 (p < .001)。没有发现上皮溃疡或纤维化的组织学证据发生显着变化，而地塞米松组的炎症程度有所增加（p = .04）。在急性喉部烧伤模型中，与未涂层的 ETT 相比，局部地塞米松递送增加了 VF 硬度和炎症程度，这反映在吸入烧伤模型的早期生物力学和组织学变化中。
Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug‐eluting electrospun polymer‐mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Dexamethasone‐loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated‐indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two‐way ANOVA with Tukey's post hoc test and Wilcoxon rank‐sum test. VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04). Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.
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