THE EFFECT OF PENTOXIFYLLINE ON ACID-INDUCED ALVEOLAR EPITHELIAL INJURY

Background: Acid instillation into one lung is known to cause an increase in the permeability of the endothelium to protein in both the instilled and the contralateral lungs. Activated neutrophils are believed to be involved in causing this increased permeability. Pentoxifylline, a drug used in clinical practice, has multiple effects on neutrophils, including inhibition of phagocytosis, degranulation, and superoxide generation. This study investigated whether pretreatment with pentoxifylline would protect the alveolar epithelium or lung endothelium from injury. Methods: The effect of acid instillation into one lung of anesthetized rabbits using several quantitative parameters was investigated. The quantification of the bidirectional movement of the alveolar (I-125-albumin) and the circulating protein tracers (I-131-albumin) was used as a measurement of the permeabilities of the lung epithelium and the lung endothelium in the acid-instilled lung, Bronchoalveolar lavage and measurement of the entry of the circulating protein tracer were used to assess the permeabilities of these barriers in the noninstilled lung. Results: The instillation of HCl (pH 1.25, 1.2 ml/kg) into the right lung resulted in an increase in the protein permeability of the right lung's alveolar epithelium and endothelium as well as an increase in the permeability to protein of the left lung's endothelium. Pentoxifylline pretreatment attenuated the increase in the endothelial permeability of both lungs by 50% and restored the Pa-o2/FIo2 to normal in the pretreated animals exposed to acid injury. Conclusions: Acid aspiration causes a dramatic increase in the alveolar epithelial permeability of the acid-instilled lung, but the permeability of the alveolar epithelium of the contralateral lung remains normal. In contrast, unilateral acid instillation causes an increase in the permeability of the endothelium of both lungs. The increase in endothelial permeability can be attenuated by pretreatment with pentoxifylline administration, and this leads to restoration of normal gas exchange.