Experimental Studies on the Effects of Adrenocorticosteroid in the Rabbits Given Diphtheria Toxin

Kim, Tae Woon

Abstract

Effects of adrenocorticosteroid in the rabbits given repeated sublethal doses of diphtheria toxin were studied with respects to survival time, electrocardiographic behavior, change in serum potassium, and histopathology of the heart, kidney and adrenal gland. Experiments were performed twice with different doses of toxin and prednisolone and with different methods of administration. In the first experiment, all fourteen rabbits received daily subcutaneous injections of 0.1 M.L.D. of toxin per kg of body weight for three consecutive days, and eight of them received daily intramuscular injections of 6mg of prednisolone per kg of body weight beginning soon after the first injection of toxin until death. In the second experiment, all sixteen rabbits received subcutaneous injections with daily doses of 0.2, 0.3, 0.4, 0.5, 0.6 and 0.7 M.L.D. of toxin per kg of body weight in this order for six consecutive days, and nine of them received daily intramuscular injections of 10mg of prednisolone per kg of body weight beginning two days prior to the first injection of toxin until death. As control groups, six rabbits in the first experiment and seven in the second, received daily intramuscular injections of normal saline for the same period. Electrocardiograms were taken in six rabbits given intravenous KCI solution only to compare the findings with those of the first and second experimental animals. The results are as follows: 1. In the first experiment, mean survival times were 118.024.6 hours in the prednisolone-treated group and 145.842.6 in the control and in the second experiment, 159.226.1 in the prednisolone-treated group and 176.324.1 in the control. The difference was not statistically significant in the first experiment while significant in the second. 2. Major electrocardiographic findings consisted of tenting of T wave, change in S-T segment, inversion of T wave, widening of QRS duration and P-R interval, deviation of QRS axis, disappearance of P wave and decrease in heart rate. No significant differences were found between the prednisolone-treated and control groups. In general, electrocardiographic patterns showed marked similarities to those of progressive hyperpotassemia. 3. After toxin injection, hyperpotassemia developed and progressed to 11.2 mEq/1 (mean) just before death. No significant differences were found between the prednisolone-treated and control groups. 4. Electrocardiographic findings in six rabbits given intravenous KCI solution only were similar to those of the toxin-treated rabbits with or without prednisolone administration, in which left deviation of QRS axis and inversion of T wave in lead I and V6 were also observed in addition to other hyperpotassemia findings. 5. Gross findings at autopsy showed; a) Multiple petechiae were frequently observed on the surface of the kidney. b) Brownish black discoloration of the adrenal gland probably due to hemorrhage and necrosis was found mainly in the rabbits of preliminary study group given relatively large doses of toxin. c) Abnormalities were rare in the heart. 6. Microscopically, the kidney showed more pronounced change than those of the heart and the adrenal gland. In the kidney, severe dilatation of the glomerular capillary with fibrin thrombi, many casts in the tubule, and relatively mild tubular degeneration and dilatation were observed in most cases. Interstitial hemorrhage was also seen in some cases, but necrosis was rare. In the heart, granular degeneration of the muscle cell and interstitial hemorrhage were relatively prominent in most cases. Mild myocytolysis and fibrin thrombi in interstitium were also observed frequently, but interstitial infiltration, loss of striation and myocardial necrosis were rare. Fatty change of the muscle cell, although found in most, was very mild. In the adrenal gland, cortical hemcorrhage and necrosis were found mainly in the rabbits of preliminary study group. Among the findings mentioned above, dilatation of the glomerular capillary with fibrin thrombi and interstitial hemorrhage in the kidney were more pronounced in the prednisolone-treated groups than in the control. 7. Fibrin thrombi observed in the kidney and the heart suggest that disseminated intravascular coagulation was developed during toxemia.

Experimental Studies on the Effects of Adrenocorticosteroid in the Rabbits Given Diphtheria Toxin

Abstract

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