ACE inhibition attenuates radiation-induced cardiopulmonary damage

• Published in: Radiotherapy and oncology 2015-01, Vol.114 (1), p.96-103
• Main Authors: van der Veen, Sonja J, Ghobadi, Ghazaleh, de Boer, Rudolf A, Faber, Hette, Cannon, Megan V, Nagle, Peter W, Brandenburg, Sytze, Langendijk, Johannes A, van Luijk, Peter, Coppes, Robert P
• Format: Article
• Language: English
• Subjects: ACE inhibition; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Captopril; Captopril - pharmacology; Heart - radiation effects; Hematology, Oncology and Palliative Medicine; Lung - radiation effects; Male; Radiation Injuries - prevention & control; Radiation-induced cardiac toxicity; Radiation-induced lung toxicity; Rats, Wistar; Respiratory Rate - radiation effects; Thoracic Neoplasms - radiotherapy; Thoracic tumors; Vascular Remodeling - radiation effects
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2014.11.017

Abstract 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.