Prevention and treatment of functional and structural radiation injury in the rat heart by pentoxifylline and alpha-tocopherol.
OBJECTIVE
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
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 alpha-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 mum(2) per 100 mum(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 left ventricular function, both when started before irradiation and when started later during the process of RIHD.
Boerma
Marjan
M
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. mboerma@uams.edu
Roberto
Kerrey A
KA
Hauer-Jensen
Martin
M
D000818:Animals; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003599:Cytoskeleton / Q000528:radiation effects; D003971:Diastole; D005355:Fibrosis; D006321:Heart / Q000528:radiation effects*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000528:radiation effects; D009206:Myocardium / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000627:therapeutic use*
D024042:Collagen Type I; D024061:Collagen Type III; D011837:Radiation-Protective Agents; D024502:alpha-Tocopherol; D010431:Pentoxifylline