TY - JOUR
T1 - ACE inhibition attenuates radiation-induced cardiopulmonary damage
AU - Van Der Veen, Sonja J.
AU - Ghobadi, Ghazaleh
AU - De Boer, Rudolf A.
AU - Faber, Hette
AU - Cannon, Megan V.
AU - Nagle, Peter W.
AU - Brandenburg, Sytze
AU - Langendijk, Johannes A.
AU - Van Luijk, Peter
AU - Coppes, Robert P.
N1 - Publisher Copyright:
© 2014 Elsevier Ireland Ltd. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Background and purpose:In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that combined irradiation intensifies cardiopulmonary toxicity. Unfortunately, current clinical practice does not include preventative measures to attenuate radiation-induced lung or cardiac toxicity. Here, we investigate the effects of the ACE inhibitor captopril on radiation-induced cardiopulmonary damage. Material and methods: After local irradiation of rat heart and/or lungs captopril was administered orally. Cardiopulmonary performance was assessed using biweekly breathing rate measurements. At 8 weeks post-irradiation, cardiac hemodynamics were measured, CT scans and histopathology were analyzed. Results Captopril significantly improved breathing rate and cardiopulmonary density/structure, but only when the heart was included in the radiation field. Consistently, captopril reduced radiation-induced pleural and pericardial effusion and cardiac fibrosis, resulting in an improved left ventricular end-diastolic pressure only in the heart-irradiated groups. Conclusion: Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.
AB - Background and purpose:In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that combined irradiation intensifies cardiopulmonary toxicity. Unfortunately, current clinical practice does not include preventative measures to attenuate radiation-induced lung or cardiac toxicity. Here, we investigate the effects of the ACE inhibitor captopril on radiation-induced cardiopulmonary damage. Material and methods: After local irradiation of rat heart and/or lungs captopril was administered orally. Cardiopulmonary performance was assessed using biweekly breathing rate measurements. At 8 weeks post-irradiation, cardiac hemodynamics were measured, CT scans and histopathology were analyzed. Results Captopril significantly improved breathing rate and cardiopulmonary density/structure, but only when the heart was included in the radiation field. Consistently, captopril reduced radiation-induced pleural and pericardial effusion and cardiac fibrosis, resulting in an improved left ventricular end-diastolic pressure only in the heart-irradiated groups. Conclusion: Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.
UR - http://www.scopus.com/inward/record.url?scp=84925070884&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2014.11.017
DO - 10.1016/j.radonc.2014.11.017
M3 - Article
C2 - 25465731
AN - SCOPUS:84925070884
SN - 0167-8140
VL - 114
SP - 96
EP - 103
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 1
ER -