Total Exclusion from External Respiration Protects Lungs from Development of Fibrosis after Paraquat Intoxication

Abstract

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. In this study we have shown that total exclusion from ventilation prevents the development of lung fibrosis after paraquat intoxication.