Cardiac Mural Thrombi Caused by Radiation

Abstract

Clinical and pathologic observations since 1966 have proved that the human heart is sensitive to the effects of ionizing radiation (1-3). Both myocardium and pericardium may suffer characteristic lesions when irradiated in the course of treatment of thoracic tumors. The end results are severe pericardial fibrosis, pericardial effusion, and diffuse myocardial fibrosis (2). These lesions are dose dependent and may cause heart failure and death, mainly through the mechanism of pericardial tamponade or pericardial constriction (3). Identical lesions have been produced in New Zealand white rabbits using a single local dose of 2000 rads or fractionated radiation (5400 rads in 12 equal fractions over 28 elapsed days: 2060 rets) (4). Electron microscopic studies of the rabbit model indicate that the capillary endothelial cell is the critical site of injury in the irradiated myocardium (5, 6). Its damage causes capillary thrombosis or rupture, which in turn produce insufficiency of the microcirculation. The resulting ischemia leads to the final diffuse myocardial fibrosis. The dose response of heart and pericardium was studied in 192 male C3H/Km mice weighing 28-33 g. These mice were divided into 16 groups of 12 animals each. One group received no treatment. The mice in the remaining 15 groups received single doses of x-irradiation to the heart varying from 1200-4000 rads (in 200-rad increments), from a 250-kV source (7). The end point of this experiment was to be death due to the radiation-induced heart failure, which occurs in approximately 50% of rabbits receiving a single dose of 2000 rads (4). But the expected wave of deaths never occurred in the mice, even after a period of observation of 180 days (rabbits usually die between 70 and 150 days after a single dose of 2000 rads); indeed, the only clinical signs that the mice had been exposed to radiation were the characteristic depigmentation and epilation of skin in the pathway of the beam. Furthermore, the necropsies of mice sacrificed at 180 days showed no trace of the expected diffuse myocardial fibrosis, pericardial fibrosis, or pericardial effusion. Instead, the hearts of mice exposed to 2000 rads or more revealed ventricular mural thrombi composed of fibrin with varying degrees of collagen replacement (Fig. 1). The extension of these thrombi and the proportion of collagen were dose-dependent. None of the age-matched unirradiated control mice had such thrombi (7).