Mechanisms of late cardiac radiation injury

Cardiac injury is a late side effect of radiotherapy treatments in which the heart is situated in the radiation field. The observed myocyte loss is not likely to be a direct effect of irradiation, since cardiac myocytes are known to remain functional after high radiation doses. The purpose of this study was to elucidate mechanisms that are responsible for myocyte loss and fibrosis after irradiation. In a rat model, different histopathological characteristics were determined after local heart irradiation with a single dose between 15 and 22.5 Gy and compared with hearts of rats that had been treated with the radioprotector amifostine (ethyol). Myocardial lesions as fibrosis, degeneration and inflammation were often observed in the endocardial layer of the ventricles, a region of the heart which is known to be most sensitive in situations of deprived blood supply. Changes, observed in coronary arteries, included a loss of smooth muscle cells, fibrosis, and enlargement of the luminal diameter. Based on their morphology, coronary arteries are likely to have lost their 'windtunnel' function, which is important to maintain blood flow. One month after irradiation, myocardial capillaries became immunoreactive for von Willebrand factor (vWf). From 3 months onwards, vWf staining was observed also within the extracellular matrix of areas with massive fibrosis and degeneration. These dose- and time dependent increases in deposition of vWf indicate the presence of damaged microvascular endothelial cells. In sections of amifostine treated rat hearts, vWf staining was increased to a lesser extent. From 3 months onwards, ventricular mast cell numbers showed a dose-dependent increase. In the left ventricle, mast cell numbers were correlated to total histopathological score. Altogether, these results suggest that upon irradiation, the heart is subjected to a decreased myocardial blood supply. Mast cells might also play an important role in the development of myocardial injury