Fogt F, Zilker T
Toxikologische Abteilung, II, Medizinische Klinik, Technische Universitaet Muenchen, West Germany.
Hum Toxicol. 1989 Nov;8(6):465-74. doi: 10.1177/096032718900800606.
Most survivors of paraquat intoxication go on to develop fibrosis of the lung leading to death within a few weeks. The pathogenic effects of paraquat are based on the formation of oxygen free radicals. A cascade reaction occurs at the cell membrane which is damaged and cell integrity is destroyed. Fibroblasts migrate into the damaged region leading to the laying down of collagen and subsequent fibrosis. Currently paraquat intoxication is treated with gastrointestinal lavage, haemoperfusion and haemodialysis with mixed results. Artificial respiration with low percentage of inspired oxygen is instituted in order to decrease the possible release of oxygen radicals. However, in most cases, developing fibrosis prevents this treatment continuing and requires increased concentrations of inspired O2 and increased ventilation pressure. The combination of increased FiO2 and barotrauma leads to a vicious circle of parenchymal lung damage. In this study we present a treatment designed to avoid the development of lung fibrosis using total exclusion of segments of the lung from external ventilation. Exclusion from external ventilation was performed in animal experiments by instillation of Ethibloc, an amino acid glue, in one main bronchus to create an atelectasis. In different experimental groups this procedure was performed before and after intraperitoneal intoxication with paraquat. Four to twelve days later the experimental animals were sacrified and the ventilated lungs and the atelectatic lungs were compared. The ventilated lungs showed dose-dependent damage to the alveolar epithelium and gross interstitial oedema. In some cases fibrosis was seen. The atelectatic parts of the lung were not different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
大多数百草枯中毒幸存者会在几周内发展为肺纤维化并导致死亡。百草枯的致病作用基于氧自由基的形成。细胞膜会发生级联反应,导致细胞膜受损,细胞完整性遭到破坏。成纤维细胞迁移至受损区域,导致胶原蛋白沉积并随后发生纤维化。目前,百草枯中毒的治疗方法包括胃肠灌洗、血液灌流和血液透析,但效果不一。采用低吸氧百分比的人工呼吸,以减少氧自由基的可能释放。然而,在大多数情况下,肺纤维化的发展会妨碍这种治疗的持续进行,需要提高吸氧浓度和通气压力。吸氧浓度增加和气压伤相结合会导致实质性肺损伤的恶性循环。在本研究中,我们提出了一种治疗方法,即通过完全排除肺段进行外部通气,以避免肺纤维化的发展。在动物实验中,通过向一条主支气管内注入氨基酸胶Ethibloc来造成肺不张,从而实现排除外部通气。在不同实验组中,该操作在腹腔注射百草枯之前和之后进行。四至十二天后,将实验动物处死,比较通气肺和肺不张肺的情况。通气肺显示出对肺泡上皮的剂量依赖性损伤和明显的间质水肿。在某些情况下可见纤维化。肺不张部分与对照组无异。(摘要截选至250词)