Injection of sodium succinate in doses of 5 or 10 mmol/kg (but not 1 mmol/kg) intensified oxygen consumption in rats with sodium thiopental-induced coma. Injection of SDH inhibitor (sodium malonate) inhibited gas exchange and abolished the effect of sodium succinate. The effect of succinate on rat survival was positive, while that of malonate was negative, but manifested only as a trend. The critical role of succinate oxidation in preventing lethal complications of barbiturate-induced coma is proved.

Sodium thiopental in the comatogenic (but not soporogenic) dose caused hyperammoniemia in rats. Blood ammonium level increased 3-fold within 3 h and 5-fold within 18 h. Blood urea level increased by one-third within 18 h against the background of unchanged creatinine level and hematocrit. Urinary excretion of ammonium did not decrease, while its release with exhaled air increased, indicating intensification of ammonium formation in the body. Barbiturate coma did not change the slope of curves of dose-dependent increase of ammonium or urea levels in the blood of rats injected with ammonium acetate, which attested to the absence of appreciable disorders in the ammonium detoxifying function of the liver. Ammonium hyperproduction could be caused by gastrointestinal stasis verified by X-ray examination and confirmed by correlation between blood urea level and stool retention in narcotized rats.

In rats with experimental thiopental coma rectal temperature decreased by 9.4 degrees C, oxygen consumption 5-fold, and arteriovenous Po(2)gradient decreased 2-fold within 3 h; CO(2)accumulated in the blood and mixed type acidosis developed. Administration of sodium succinate under these conditions increased arteriovenous Po(2)gradient and reduced manifestations of metabolic acidosis. Maintenance of normal body temperature (warming) corrected primarily manifestations of respiratory acidosis. Each therapeutic agent reduced inhibition of O(2)consumption by 1/4; animal survival tended to increase from 42 to 50%. Combined use of these treatments potentiated the antiacidotic effect and increased survival to 92%. The authors conclude that hypothermia inhibits the therapeutic effect of succinate in barbiturate coma.

The effects of various energy metabolism modifiers and their combinations on cyclophosphane toxicity are examined in the fresh-water crustacea Daphnia magna. The role of acute energy deficiency in the development of paralyzing effect of cyclophosphane is demonstrated. Transporting forms of succinic acid and combinations of carbonic acids with NAD exhibit high protective activity, while glucose reduces protective activity of NAD and sensitizing activity of amino acids.Key Words: cyclophosphane; nicotinamide; succinate; energy deficiency Neurotoxic effects of alkylating agents hamper their therapeutic application as cytostatics [5,9]. Acute intoxication by these substances shortens life span of some laboratory animals [8]. The manifestations of such intoxication [8] resemble those typical of acute energy deficiency in the nervous system, while the ability of dichloroethyl sulfide to lower NAD concentration in the cytoplasm [10] implies that this effect is exerted at the cellular level. In the present study we evaluated the role and explored the possibility of preventing energy deficiency upon paralyzing effect of cyclophosphane (CP) in the freshwater crustacean Daphnia magna. MATERIALS AND METHODSNeurological damage was modeled by adding CP to the incubation medium in concentrations suppressing motor activity of daphnia within a 5-h period. A short-term exposition allowed us practically to rule out cytostatic effect of CP as a potential cause of death of daphnia, while a 600-fold excess of incubation medium provided constant concentration of CP throughout the experiment. The resistance to CP was estimated by ECs0, which was calculated by probit analysis (Hewlett-Packard software) of data obtained Military Medic'~ Academy, SL-l~t~mbu~j by increasing CP concentration in the incubation medium from the minimal to the absolutely lethal.Modifiers of the resistance to CP, which had no effect on motor activity of daphnia, were added 10 min before CP. The animals were deprived of food for 24 h before the experiment. The concentrations of energy substmtes in the incubation medium were close to their average tissue levels in mammals 12]. The effects of modifiers were expressed as the ratio between ECs0 of CP in the presence and in the absence of the modifier (factor of dose modification, FDM). The measurements were performed 5 times. The significance of differences was evaluated by Student's t test for paired samples [4]. RESULTSNicotinamide (NA), a precursor of NAD, increased the resistance of daphnias to CP 1.12-to 1.14-fold (Table 1). Glucose and the NAD-dependently oxidized carbonic acids pyruvate and citrate did not modify cytotoxic effect of CP and markedly altered the protective effect of NA. This effect was abolished by glucose and potentiated by carbonic acids. The amino acids glutamate and aspartate did not abolisla the effect of NA and sensitized the animals to C P.Succinate, a NAD-independently oxidized substrate, increased the resistance of daphnias to CP by 0007-4888/g8/0003-0270520.00 r Plenum Puh|ishJ.ng C~,q...

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