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ACE inhibition attenuates radiation-induced cardiopulmonary damage

van der Veen, S. J., Ghobadi, G., de Boer, R. A., Faber, H., Cannon, M. V., Nagle, P. W., Brandenburg, S., Langendijk, J. A., van Luijk, P. & Coppes, R. P., Jan-2015, In : Radiotherapy and Oncology. 114, 1, p. 96-103 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 8weeks 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.

Original languageEnglish
Pages (from-to)96-103
Number of pages8
JournalRadiotherapy and Oncology
Volume114
Issue number1
Publication statusPublished - Jan-2015

    Keywords

  • Thoracic tumors, Radiation-induced cardiac toxicity, Radiation-induced lung toxicity, ACE inhibition, Captopril, ANGIOTENSIN-CONVERTING ENZYME, CONGESTIVE-HEART-FAILURE, IRRADIATED RAT LUNG, CARDIAC INTERSTITIUM, COMPUTED-TOMOGRAPHY, CAPTOPRIL, DISEASE, FIBROSIS, CANCER, RISK

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