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
Author Information
Sonja J van der Veen: Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Ghazaleh Ghobadi: Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Rudolf A de Boer: Department of Experimental Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Hette Faber: Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Megan V Cannon: Department of Experimental Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Peter W Nagle: Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Sytze Brandenburg: Kernfysisch Versneller Instituut, Groningen, The Netherlands.
Johannes A Langendijk: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Peter van Luijk: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Robert P Coppes: Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands. Electronic address: r.p.coppes@umcg.nl.
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.
