Langenback E G, Davis J M, Robbins C, Sahgal N, Perry R J, Simon S R
Department of Pediatrics, SUNY Health Science Center, Stony Brook, New York, USA.
Pediatr Pulmonol. 1999 Feb;27(2):124-9. doi: 10.1002/(sici)1099-0496(199902)27:2<124::aid-ppul9>3.0.co;2-e.
Prophylactic, intratracheal instillation of recombinant human Cu/Zn superoxide dismutase (rhSOD) has been shown to lessen lung injury produced by 48 h of hyperoxia and mechanical ventilation in neonatal piglets. However, instillation of small volumes of rhSOD intratracheally would not be expected to result in uniform pulmonary distribution. Aerosolization is a technique that may improve pulmonary distribution of drugs, but is limited by the poor efficiency of most nebulizers. A newly modified ultrasonic nebulizer was tested to assess pulmonary distribution of rhSOD compared to that achieved by intratracheal instillation. rhSOD was dual-labeled with technetium-99m (99mTc) and a fluorescent analog (permitting quantitative and qualitative assessments of pulmonary distribution), and administered to neonatal piglets by intratracheal instillation or by aerosolization. Intratracheal instillation of rhSOD to piglets when supine resulted in nonuniform distribution, with most of the drug being found in the right caudal lobe, and localized in airways. Placing animals in 30 degrees of Trendelenburg and administering half the dose in the left and half in the right lateral decubitus positions improved distribution, but alveolar deposition remained patchy. Aerosolization using a modified ultrasonic nebulizer uniformly delivered 45.8 +/- 3.8% of the rhSOD to the lungs that had been placed in the nebulizer. The rhSOD was still active and present in airways and alveoli in a homogeneous fashion. We conclude that intratracheal instillation of rhSOD in small volumes results in nonuniform pulmonary distribution, while aerosolization enhances rhSOD distribution and alveolar deposition. This has important implications for ongoing clinical trials of rhSOD for the prevention of acute and chronic lung injury in premature neonates.
预防性气管内滴注重组人铜/锌超氧化物歧化酶（rhSOD）已被证明可减轻新生仔猪因48小时高氧和机械通气所致的肺损伤。然而，气管内滴注少量rhSOD预计不会导致肺部均匀分布。雾化是一种可能改善药物肺部分布的技术，但受大多数雾化器效率低下的限制。测试了一种新改良的超声雾化器，以评估rhSOD的肺部分布，并与气管内滴注法进行比较。rhSOD用99m锝（99mTc）和一种荧光类似物进行双标记（以便对肺部分布进行定量和定性评估），并通过气管内滴注或雾化法给予新生仔猪。仰卧位时对仔猪进行气管内滴注rhSOD会导致分布不均匀，大部分药物位于右尾叶，并局限于气道。将动物置于头低脚高30度体位，并在左侧和右侧卧位分别给予一半剂量可改善分布，但肺泡沉积仍呈斑片状。使用改良超声雾化器进行雾化可将45.8±3.8%的rhSOD均匀地输送至置于雾化器中的肺内。rhSOD仍具有活性，并以均匀的方式存在于气道和肺泡中。我们得出结论，小剂量气管内滴注rhSOD会导致肺部分布不均匀，而雾化可增强rhSOD的分布和肺泡沉积。这对正在进行的rhSOD预防早产儿急性和慢性肺损伤的临床试验具有重要意义。
