Synergistic Renal Effects of DCI and Cortisone in Mice Poisoned with Bacterial Endotoxin.

The adrenergic blocking agent DCI or 3,4-dichloroisoproterenol provided a measure of protection against bacterial endotoxin when given subcutaneously to mice by McLean and Berry(1). Cortisone had been found to protect mice from these lipopolysaccharides by Berry et al.(2,3) and the handling of nitrogenous waste products was implicated(4). In the present work the influence of DCI on nitrogen excretion and its interaction with cortisone has been investigated.

Methods. Male CF1 mice were used in this study. Saline blanks were given subcutaneously as were the doses of DCI 10 mg/kg and cortisone acetate 5 mg/mouse. Difco crystalline lipopolysaccharide from E. coli (Code 0.27:B8, Control 118023) was the endotoxin used. An approximate LD₅₀ of 0.3 mg/mouse was injected intraperitoneally. The DCI dose was given twice; 5 hours before and 1 hour before the endotoxin. The cortisone doses were given in the same way. The average weight of the mice used in these experiments was about 23 g. The micro-Kjel-dahl procedure was used for determination of urinary nitrogen and blood non-protein nitrogen (NPN). Urine was collected under toluene in conical centrifuge tubes. Pairs of mice were restrained by small stainless steel screens over glass funnels. The animals were without food and water throughout the collection period, which was 17 hours (5 P.M.-10 A.M.). For determination of NPN one volume of blood (about 1 cc) was mixed with 2 volumes of 10% trichloroacetic acid, centrifuged at 3000 RPM for 3 minutes and then filtered. One cc of the filtrate was combined with 0.5 cc 36N H₂SO₄.

Results. Three separate experiments were conducted, each with 6 values per group. Two sets of values were combined to give the data presented in Fig. 1 and the final experiment, carried out some months later than the others, confirmed the earlier findings.