Hartmann Erik K, Bentley Alexander, Duenges Bastian, Klein Klaus U, Boehme Stefan, Markstaller Klaus, David Matthias
Department of Anaesthesiology, Medical Centre of the Johannes Gutenberg-University, Langenbeckstr, 1, 55131 Mainz, Germany.
BMC Res Notes. 2013 Sep 27;6:385. doi: 10.1186/1756-0500-6-385.
The lectin-like domain of TNF-α mimicked by an inhaled TIP peptide represents a novel approach to attenuate a pulmonary edema in respiratory failure, which is on the threshold to clinical application. In extension to a previously published study, which reported an improved pulmonary function following TIP peptide inhalation in a porcine model of lavage-induced lung injury, a post-hoc comparison to additional experiments was conducted. This analysis addresses the hypothesis that oleic acid injection-induced capillary leakage and alveolar necrosis blunts the previously reported beneficial effects of TIP peptide inhalation in a porcine model.
Following animal care committee approval lung injury was induced by oleic acid injection in six pigs with a setting strictly according to a previously published protocol that was used for lung-lavaged pigs. Ventilation/perfusion-distribution by multiple inert gas elimination, parameters of gas exchange and pulmonary edema were assessed as surrogates of the pulmonary function. A significantly improved ventilation/perfusion-distribution following TIP inhalation was recognized only in the bronchoalveolar lavage model but not following oleic acid injection. The time course after oleic acid injection yielded no comparable impact of the TIP peptide on gas exchange and edema formation.
Reported beneficial effects of the TIP peptide on gas exchange and pulmonary edema were not reproducible in the oleic acid injection model. This analysis assumes that sustained alveolar epithelial necrosis as induced by oleic acid injection may inhibit the TIP-induced edema resolution. Regarding the on-going clinical development of the TIP peptide this approach should hardly be effective in states of severe alveolar epithelial damage.
吸入性TIP肽模拟的肿瘤坏死因子-α的凝集素样结构域代表了一种减轻呼吸衰竭中肺水肿的新方法，该方法正处于临床应用的门槛。在先前发表的一项研究基础上进行了扩展，该研究报道了在猪灌洗诱导的肺损伤模型中吸入TIP肽后肺功能得到改善，并与其他实验进行了事后比较。本分析旨在验证以下假设：油酸注射诱导的毛细血管渗漏和肺泡坏死会削弱先前报道的TIP肽吸入在猪模型中的有益效果。
在动物护理委员会批准后，按照先前用于肺灌洗猪的方案，对6头猪进行油酸注射诱导肺损伤。通过多惰性气体消除法评估通气/灌注分布、气体交换参数和肺水肿，作为肺功能的替代指标。仅在支气管肺泡灌洗模型中，吸入TIP后通气/灌注分布有显著改善，而在油酸注射后则没有。油酸注射后的时间进程显示，TIP肽对气体交换和水肿形成没有类似影响。
在油酸注射模型中，TIP肽对气体交换和肺水肿的有益作用无法重现。该分析认为，油酸注射诱导的持续性肺泡上皮坏死可能会抑制TIP诱导的水肿消退。鉴于TIP肽正在进行的临床开发，这种方法在严重肺泡上皮损伤状态下可能几乎无效。
