Abstract
The Use of thorium dioxide (Thorotrast) for hepatolienography was first described by Radt in 1930. It was widely employed before its delayed toxic effects were appreciated and served to demonstrate the clinical value of roentgen opacification of the liver and spleen (1). At present, however, the liver and spleen remain among the few structures of the body for which a safe, reliable diagnostic radiographic technic is not available. This communication reports studies with a microparticulate suspension of tetraiodophenolphthalein, a compound of iodine having low solubility in water. After intravenous injection, this radiopaque material is deposited in the reticuloendothelial cells of the liver and spleen (Fig. 1). Although the solubility of tetraiodophenolphthalein is low, it is slowly released from the reticuloendothelial cells of the liver and spleen and is ultimately excreted from the body. Methods Microparticulate suspensions of tetraiodophenolphthalein were prepared by prolonged wet grinding in a roller mill. They were then allowed to settle in a cylinder. By varying the sedimentation period, it was possible to obtain samples with particle sizes ranging from 5 μ to less than 1.0 μ. Estimates of particle size were made by microscopic observation of suspension samples with use of an eyepiece calibrated with a stage micrometer. Some of the particles, however, were beyond the resolution of an ordinary optical microscope. Selected samples were examined and photographed by electron microscopy to determine maximum particle size and range (Fig. 2). Rats weighing 250 to 350 g were given 500 to 1,000 mg per kilogram of tetraiodophenolphthalein suspension through a surgically exposed femoral vein while under light ether anesthesia. Suspensions were made to a dose volume of 4 ml and injected slowly over a period of two hours by a Harvard infusion pump. Animals were examined by x-ray immediately after completion of the injection and serially until sacrificed from one day to eight months later. They were then exsanguinated from the aorta, and plasma was obtained for the determination of aspartate transaminase, alkaline phosphatase, and bilirubin. Liver, spleen, lung, and kidney were fixed in formol saline and sections prepared by paraffin and frozen technic. Selected animals were given intravenous bilirubin tolerance tests at one to eleven days after opacification of the liver and spleen. In the tolerance test, 1 mg of bilirubin dissolved in 0.1 molar sodium bicarbonate per 100 g body weight was injected intravenously. Bilirubin was then estimated in blood samples taken from the tail vein after five minutes, thirty minutes, one hour, and four hours and compared with a control sample.
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