EFFECT OF HIGH-DOSE PENTOXIFYLLINE ON ACUTE RADIATION-INDUCED LUNG TOXICITY IN A RAT LUNG PERFUSION MODEL

Purpose: The purpose of this study was to study the effect of high-dos e oral pentoxifylline on radiation-induced acute lung injury as assess ed with a rat lung perfusion model. Methods and Materials: Adult male Sprague-Dawley rats were used throughout this study, A preliminary exp eriment determined that treatment with 2 g/liter pentoxifylline in dri nking water resulted in an average consumption of 1.38 g/m(2)/day, whi ch is comparable to the maximum tolerated dosage in humans, Seventy-tw o rats were irradiated to the left hemithorax with single fraction dos es ranging from 10 through 18 Gy. Half were treated with 2 g/liter pen toxifylline in drinking water from 1 week before radiation through 8 w eeks after radiation, Lung vascular perfusion scanning was performed a t 3, 4, 5, 6, and 8 weeks after radiation using (99)mTc-macroaggregate d albumin. The lung perfusion ratio was defined as the number of count s due to radioactivity within the irradiated left lung region of inter est divided by the number of counts within the region of the nonirradi ated right lung, This lung perfusion ratio has been shown to decrease with radiation-induced lung injury. Results: Although radiation led to a decreased lung perfusion ratio in all groups, those receiving pento xifylline maintained higher ratios than irradiated controls from 3-5 w eeks, especially for those receiving 15 or 18 Gy, However, from 6 thro ugh 8 weeks the irradiated controls exhibited partial recovery of lung perfusion ratio, whereas the pentoxifylline groups did not, By 8 week s after 15 and 18 Gy, lung perfusion ratios were significantly higher for the irradiated controls than for pentoxifylline-treated rats-a rev ersal of the pattern observed at 3-5 weeks. Conclusions: The protectio n by pentoxifylline against radiation-induced acute lung injury was tr ansient and limited to the first 5 weeks after radiation, Subsequent r ecovery from lung injury was inhibited by this drug at later times wit hin the acute phase.