Radiation-induced cardiopulmonary dysfunction: Pathophysiology & Intervention strategies

Sjoerdtje Johanna van der Veen

    Research output: ThesisThesis fully internal (DIV)

    604 Downloads (Pure)

    Abstract

    Radiotherapy is an important treatment modality for thoracic tumours. Unfortunately, the radiation dose is restricted by the risk of normal-tissue toxicity of the surrounding healthy tissues such as the lung and heart.
    In this thesis we aimed to get more insight into the pathophysiology of radiation-induced cardiopulmonary dysfunction (RICPD) to find new/better predictors of the development and possible attenuating intervention strategies of RICPD.
    In our rat model, we found that besides inflammation pulmonary vascular damage and remodelling play a critical role in the development of early RICPD. In addition, damage in heart and lungs were found to secondarily damage the other and combined irradiation even enhances the toxicity. These findings may help improve biophysical models to predict RICPD. Moreover, our findings provide new insights how to diminish/repair RICPD, such as the observed ameliorating effect of the ACE inhibitor captopril directly on early heart toxicity and indirectly via its interaction with early lung toxicity. Moreover, preliminary results indicated that transplantation of endothelial progenitor cells may ameliorate RICPD by repairing vascular damage.
    To conclude, translation of these preclinical findings to clinic may improve radiotherapy treatment and even provide tumour dose escalation leading to a better tumour control and increase survival of the patient.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Coppes, Rob, Supervisor
    • Langendijk, Johannes Albertus, Supervisor
    • van Luijk, Peter, Co-supervisor
    Award date2-Nov-2016
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-90-367-9151-9
    Electronic ISBNs978-90-367-9148-9
    Publication statusPublished - 2016

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