Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol

Purpose: Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX) and alpha-tocopherol on cardiac injury in a rat model of RIHD. Methods and Materials: Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for 6 months after irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and a-tocopherol (20 IU/kg/day) and received these compounds either from 1 week before until 6 months after irradiation or starting 3 months after irradiation, a time point at which histopathologic changes become apparent in our model of RIHD. Results: Radiation-induced increases in left ventricular diastolic pressure (in mm Hg: 35 +/- 6 after sham-irradiation, 82 +/- 11 after irradiation) were significantly reduced by PTX and alpha-tocopherol (early treatment: 48 +/- 7; late treatment: 53 +/- 6). PTX and alpha-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 +/- 0.2 mu m(2) per 100 mu m(2), early treatment: 2.7 +/- 0.8; late treatment: 2.2 +/- 0.2) and III (radiation only: 13.9 +/- 0.8; early treatment: 11.0 +/- 1.2; late treatment: 10.6 +/- 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and alpha-tocopherol. Conclusions: Treatment with PTX and alpha-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and fell ventricular function, both when started before irradiation and when started later during the process of RIHD. (C) 2008 Elsevier Inc.