ACE inhibition attenuates radiation-induced cardiopulmonary damage

Sonja J. van der Veen, Ghazaleh Ghobadi, Rudolf A de Boer, Hette Faber, Megan V Cannon, Peter W Nagle, Sytze Brandenburg, Johannes A Langendijk, Peter van Luijk, Robert P Coppes

Research output: Contribution to journalArticleAcademicpeer-review

76 Citations (Scopus)
227 Downloads (Pure)

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 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
DOIs
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

Cite this