Physiological interaction of heart and lung in thoracic irradiation

Abstract

Introduction: The risk of early radiation-induced lung toxicity (RILT) limits the dose and efficacy of radiation therapy of thoracic tumors. In addition to lung dose, coirradiation of the heart is a known risk factor in the development RILT. The aim of this study was to identify the underlying physiology of the interaction between lung and heart in thoracic irradiation.

Methods and materials: Rat hearts, lungs, or both were irradiated to 20 Gy using high-precision proton beams. Cardiopulmonary performance was assessed using breathing rate measurements and F(18)-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) scans biweekly and left- and right-sided cardiac hemodynamic measurements and histopathology analysis at 8 weeks postirradiation.

Results: Two to 12 weeks after heart irradiation, a pronounced defect in the uptake of (18)F-FDG in the left ventricle (LV) was observed. At 8 weeks postirradiation, this coincided with LV perivascular fibrosis, an increase in LV end-diastolic pressure, and pulmonary edema in the shielded lungs. Lung irradiation alone not only increased pulmonary artery pressure and perivascular edema but also induced an increased LV relaxation time. Combined irradiation of lung and heart induced pronounced increases in LV end-diastolic pressure and relaxation time, in addition to an increase in right ventricle end-diastolic pressure, indicative of biventricular diastolic dysfunction. Moreover, enhanced pulmonary edema, inflammation and fibrosis were also observed.

Conclusions: Both lung and heart irradiation cause cardiac and pulmonary toxicity via different mechanisms. Thus, when combined, the loss of cardiopulmonary performance is intensified further, explaining the deleterious effects of heart and lung coirradiation. Our findings show for the first time the physiological mechanism underlying the development of a multiorgan complication, RILT. Reduction of dose to either of these organs offers new opportunities to improve radiation therapy treatment of thoracic tumors, potentially facilitating increased treatment doses and tumor control.