title: ACE inhibition attenuates radiation-induced cardiopulmonary damage.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Sonja J
authors.initials: SJ
authors.lastname: van der Veen
authors.affiliation: 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.
authors.forename: Ghazaleh
authors.initials: G
authors.lastname: Ghobadi
authors.affiliation: Department of Experimental Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: de Boer
authors.affiliation: 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.
authors.forename: Hette
authors.initials: H
authors.lastname: Faber
authors.affiliation: Department of Experimental Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Megan V
authors.initials: MV
authors.lastname: Cannon
authors.affiliation: 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.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nagle
authors.affiliation: Kernfysisch Versneller Instituut, Groningen, The Netherlands.
authors.forename: Sytze
authors.initials: S
authors.lastname: Brandenburg
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Luijk
authors.affiliation: 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.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Coppes
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D006321:Heart / Q000528:radiation effects*; D008168:Lung / Q000528:radiation effects*; D008297:Male; D011832:Radiation Injuries / Q000517:prevention & control*; D017208:Rats, Wistar; D056152:Respiratory Rate / Q000528:radiation effects; D013899:Thoracic Neoplasms / Q000532:radiotherapy; D066253:Vascular Remodeling / Q000528:radiation effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril
keywords: ACE inhibition; Captopril; Radiation-induced cardiac toxicity; Radiation-induced lung toxicity; Thoracic tumors