Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

• Published in: Thorax Vol. 67; no. 4; pp. 334 - 341
• Main Authors: Ghobadi, G, Bartelds, B, van der Veen, S J, Dickinson, M G, Brandenburg, S, Berger, R M F, Langendijk, J A, Coppes, R P, van Luijk, P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Thoracic Society 01.04.2012; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Analysis of Variance; Animals; Apoptosis; Biological and medical sciences; Cardiology. Vascular system; cytokine biology; drug-induced lung disease; Edema - pathology; endothelial cell loss; Endothelium, Vascular - radiation effects; Experiments; Heart failure; Hemodynamics; histology/cytology; Histopathology; Hypertension, Pulmonary - pathology; Linear Models; Lung - pathology; Lung - radiation effects; Lung cancer; lung physiology; Lungs; Male; Medical sciences; Morphology; Pneumology; primary pulmonary hypertension; Protons; Pulmonary arteries; Pulmonary Artery - radiation effects; Pulmonary hypertension; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Radiation Injuries - pathology; radiation pneumonitis; Rats; Rats, Wistar; Rodents; vascular remodelling; Respiratory disease; Lung; Blood vessel; Irradiation; Cardiovascular disease; Anesthesia; Circulatory system; Cardiology; Artery; Pulmonary hypertension
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thoraxjnl-2011-200346

BackgroundPulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an important role in the development of radiation-induced pulmonary toxicity. Therefore, the authors investigated whether irradiation of the lung also induces pulmonary hypertension.MethodsDifferent sub-volumes of the rat lung were irradiated with protons known to induce different levels of pulmonary vascular damage. ResultsEarly loss of endothelial cells and vascular oedema were observed in the irradiation field and in shielded parts of the lung, even before the onset of clinical symptoms. 8 weeks after irradiation, irradiated volume-dependent vascular remodelling was observed, correlating perfectly with pulmonary artery pressure, right ventricle hypertrophy and pulmonary dysfunction.ConclusionsThe findings indicate that partial lung irradiation induces pulmonary vascular remodelling resulting from acute pulmonary endothelial cell loss and consequential pulmonary hypertension. Moreover, the close resemblance of the observed vascular remodelling with vascular lesions in PAH makes partial lung irradiation a promising new model for studying PAH.