Radiation-induced damage of the Wistar rat heart: biochemistry and function.

A time sequence study was performed on Wistar rats to investigate the early effects of radiation on the mechanical function and energy metabolism of the heart. Two series of rats were exposed to 20 Gy electron irradiation to a field including the heart and approximately a third of the lungs. The hearts were excised at varying time intervals (8-180 days) post irradiation. In one series of hearts the mechanical function was measured using the isolated perfused working rat heart model. At the end of the perfusion the hearts were freeze-clamped for analysis of the high energy phosphate contents (ATP, ADP, AMP and creatine phosphate). In the second series, mitochondria were isolated and the oxidative phosphorylation function measured polarographically (substrate: glutamate). Maximal depression of mechanical function was observed at 60 days post irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days. The mitochondrial oxidative phosphorylation function (as measured on the total mitochondrial population) was significantly depressed 30-120 days post irradiation. As in the case of the mechanical changes, the depression was transient and after 180 days post irradiation, values similar to those of controls were obtained. Myocardial high energy phosphates remained unaltered throughout the experiment.

Radiation-induced changes in the ultrastructure and mechanical function of the rat heart.

A time sequence study was performed to study the early effects of radiation on the ultrastructure of the rat heart. Wistar rats were exposed to 20 Gy electron irradiation to a field including the heart and a third of the lung. The hearts were excised at varying time intervals (1 h-180 days), and the ultrastructure of perfusion-fixed subepicardium and subendocardium studied. Changes were observed in both myocytes and interstitium at all time intervals. The most pronounced change observed in the myocyte was that of intercalated disc damage which reached a peak at 30 days post-irradiation. Mitochondrial damage, characterized by swelling and fenestration in areas of myofibrillar contracture, was focal and relatively scarce. Swelling of the capillary endothelial cells and collapse of the capillaries were marked up to 60 days. Of significance was the observation that the damage to both myocytes and interstitium receded after 60 days and the hearts exhibited an almost normal ultrastructure from 100 to 180 days post-irradiation. Mechanical function of these hearts followed a similar pattern: maximal depression was observed 60 days after irradiation. Thereafter the work performance of these hearts improved significantly, almost reaching control levels after 180 days.

A study of the mantle technique for Hodgkins disease using thermoluminescent dosimetry.

A study of the mantle technique for Hodgkins disease patients was embarked upon using thermoluminescent dosimetry (TLD) and a RANDO phantom. There was concern that the technique using Co-60 and turning the patient over for the posterior field may not be optimal as it was felt that the axillary areas of these patients were being under-dosed. A variety of treatment set-ups were performed on a 60-Cobalt unit at extended SSD. The phantom was planned for treatment lying supine for the anterior field and prone for the posterior field. Measurements were made in the neck, hilum and axillae using various combinations of compensators and lead filters. The combination of full field compensators and a lead filter gave the best results in the phantom but did not give satisfactory axillary readings in the patient situation. This was attributed to the difference in shape and AP separation of the patient when lying prone. RANDO, being solid, retains its shape. Treatment was then planned for a 6 MV linear accelerator using a vertical couch extender which enables the patient to remain supine throughout the treatment by increasing the table height to allow the posterior portal to be treated through the couch. Full field compensation was found to give an adequate dose to all the measured areas. This technique has since been performed on 28 patients being treated for Hodgkins disease at the Hillbrow Hospital, and the average axillary dose recorded in these patients is 88.6% of the prescribed dose.

Ratio of cardiopulmonary blood volume to stroke volume as an index of cardiac function in animals in man.

A scintillation probe was used to record a radiocardiogram as 99mTc flowed through the heart with the first pass after an intravenous injection. The ratio of cardiopulmonary blood volume to stroke volume, which could be determined indirectly from the simultaneous recording of a radiocardiogram and an electrocardiogram, was found to be a very sensitive and reliable index to describe the efficiency of the pump function of the heart with the different models of heart disease induced in experimental animals. It was found that left ventricular, right ventricular and biventricular failures were reflected by a large increase and pulmonary emboli by a decrease in the value of this index, which was named the cardiopulmonary flow index (CPFI). The technique has also been tested on a number of control and heart patients. The general principles found for animals could also be applied to man. As this is a noninvasive bedside technique it may have an important implication for the diagnosis of heart disease.