Experimental Radiation-Induced Heart Disease in Rabbits

Abstract

In recent studies (1–3) we found that significant heart disease developed in a representative series of patients whose hearts had been irradiated incidental to fractionated x-ray therapy for various intrathoracic malignant tumors. Lesions of pericardium or myocardium or both were seen five to thirty-six months after all or most of the heart was irradiated, usually to doses of at least 4,000 rads. The severity of the cardiac damage was generally proportional to the dose. These data suggest that radiation-induced heart disease may be a more frequent and important complication than is generally recognized. The concept that the heart is a highly radioresistant organ should be challenged, and its responsiveness to irradiation should be reevaluated in terms of modern radiotherapy technics and equipment. Much important data can be obtained from animal experiments, but previous reports have usually supported the notion that the normal heart can tolerate very high doses of irradiation. For instance, Leach and Sugiura (4, 5) treated rats with single doses of kilovoltage x-ray ranging from 750 to 20,000 R and found no effect upon the heart with doses less than 10,000 R. All those given 10,000 R or more died of cardiac lesions. Phillips et al. (6) in dogs and Bishop et al. (7) in rodents described severe functional abnormalities and myocardial fibrosis or necrosis following single doses of 6,000 to 9,600 R to the heart. Efskind (8) produced fatal myocardial damage in rabbits with 8,000 R. We have performed preliminary experiments in rabbits with two aims: (a) to see if radiation-induced heart lesions, as seen in humans, could be duplicated in these animals with well collimated high-energy x-irradiation at doses lower than those used by previous investigators; and (b) to establish a reliable animal model with a high yield of lesions which develop in a reasonable period of time in order to study the mechanism and evolution of the lesions. Materials And Methods Forty-six New Zealand white rabbits of both sexes, six to ten weeks old and weighing 1,500 to 2,300 g, were divided into five groups as shown in TABLE I. All were fed the same standard Purina diet with water ad libitum, and they were observed and weighed weekly. The animals were immobilized supine for irradiation on a support providing full back-scatter and were not anesthetized. Irradiation was given as a single dose by a direct anterior field including all the heart, as verified by roentgenograms. A 280 keV source (16.6 cm F.S.D., h.v.l. 2.5 mm Cu, 662 R/min., circular field 3.2 cm in diameter) was used for groups 1, 2, and part of 3, and a 6 MeV linear accelerator (64 cm S.S.D., approximately 1,000 rads/min. at maximum, 3X3 cm square) for group 4 and most of group 3.