App E M, Tomkiewicz R P, Hahn H L, Engler H, Vergin H, King M
Department of Pneumology, Albert-Ludwigs-University Freiburg, Germany.
Pulm Pharmacol Ther. 1997 Oct-Dec;10(5-6):271-6. doi: 10.1006/pupt.1998.0103.
Tasuldine (Ts) is an orally active bronchosecretolytic agent shown to be clinically effective in human studies. Tasuldine decreases the sialomucin content of the mucus and, in animal studies, this modulation of the glycopeptide correlates with decreased mucus viscosity. The aim of this study was to evaluate the effect of tasuldine on mucus viscoelasticity and correlate the rheological changes to mucociliary and cough clearability. Tracheal mucus samples were collected from anaesthetized adult ferrets by a modification of the cytology brush technique. Mucus was collected prior to and following administration of either vehicle (normal saline) or Ts (10 mg/kg i.v.), and followed by acetylcholine (ACH) challenge (ca. 4 ml of 10(-2)M i.v., slow infusion). The analysis included magnetic microrheometry to measure the viscosity and elasticity of microlitre quantities of mucus. Mucociliary transportability (NFPTR) was measured by means of the frog palate assay and mucus collection rates (mg/min) were used as an indirect measure of secretion rate. The principal index of mucus rigidity, log G*, decreased with tasuldine infusion (P = 0.014) and further decreased with ACH (P = 0.002). In simple terms, the mucus became less rigid or more deformable with tasuldine administration, thus benefiting clearability based on predictions from model studies. The changes observed with acetylcholine alone were consistent with a classic secretagogue response--the outputting of a large volume of watery mucus. NFPTR increased with tasuldine treatment, and even further with acetylcholine; however, the combination of Ts and ACH resulted in a decrease in NFPTR close to baseline, which was likely due to the fact that the resulting mucus was too liquid for maximal mucociliary efficiency. The index of mucus flux (mg/min) was very much elevated with ACH compared with control; this was not the case with Ts. This indicates that tasuldine, despite improving the rheological properties of the mucus, did not stimulate hypersecretion, as was the case for acetylcholine. The changes in mucus rheology with infused tasuldine can be considered beneficial with respect to their effects on predicted mucociliary and cough clearability, supporting the clinical effectiveness of this type of mucolytic therapy in airway diseases such as chronic bronchitis. The study also illustrates the potential danger of overliquification of mucus.
塔苏地定（Ts）是一种口服活性支气管分泌物溶解剂，在人体研究中已显示出临床疗效。塔苏地定可降低黏液中的唾液黏蛋白含量，在动物研究中，这种糖肽的调节与黏液黏度降低相关。本研究的目的是评估塔苏地定对黏液黏弹性的影响，并将流变学变化与黏液纤毛清除能力和咳嗽清除能力相关联。通过改良的细胞学刷技术从麻醉的成年雪貂收集气管黏液样本。在给予赋形剂（生理盐水）或塔苏地定（10 mg/kg静脉注射）之前和之后收集黏液，然后进行乙酰胆碱（ACH）激发（约4 ml 10⁻²M静脉注射，缓慢输注）。分析包括用磁微流变学测量微升量黏液的黏度和弹性。通过蛙腭试验测量黏液纤毛运输能力（NFPTR），黏液收集率（mg/min）用作分泌率的间接指标。黏液硬度的主要指标log G*随着塔苏地定输注而降低（P = 0.014），并随着ACH进一步降低（P = 0.002）。简单来说，给予塔苏地定后黏液变得硬度降低或更易变形，因此根据模型研究的预测有利于清除能力。单独使用乙酰胆碱观察到的变化与经典的促分泌剂反应一致——大量水样黏液的排出。塔苏地定治疗后NFPTR增加，乙酰胆碱作用下增加得更多；然而，塔苏地定和ACH联合导致NFPTR降至接近基线水平，这可能是由于产生的黏液过于稀薄而无法达到最大黏液纤毛效率。与对照组相比，ACH使黏液通量指数（mg/min）大幅升高；塔苏地定则不然。这表明塔苏地定尽管改善了黏液的流变学性质，但并未刺激分泌过多，而乙酰胆碱则会。输注塔苏地定后黏液流变学的变化就其对预测的黏液纤毛清除能力和咳嗽清除能力的影响而言可被认为是有益的，这支持了这种黏液溶解疗法在慢性支气管炎等气道疾病中的临床疗效。该研究还说明了黏液过度液化的潜在危险。
