Showing papers on "Animal mortality published in 1995"

Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: pharmacological evaluation of nitric oxide synthase inhibitors.

Abstract: The benefits of nitric oxide synthase (NOS) inhibitors in the treatment of endotoxemia or sepsis presumably arise from inhibition of the type II (inducible) NOS. However, inasmuch as the effect of these inhibitors on NOS function in vivo is rarely assessed, NOS activity was evaluated in rats and mice by measuring changes in plasma nitrite and nitrate concentrations ([NOx]) after administration of lipopolysaccharide (LPS). In both species, [NOx] peaked at 20 hr, returning to base line by 48 to 72 hr. The ED50 values (dose that elicited a 50% inhibition of the LPS-dependent increase in [NOx] 6 hr after LPS administration) for L-NG-monomethylarginine acetate, L-NG-nitroarginine methyl ester and aminoguanidine (administered 3 hr after LPS) were 34, 21 and 19 mg/kg in the rat and 32, 5 and 4 mg/kg in the mouse. These compounds also decreased the survival of LPS-challenged animals, which in the case of L-NG-nitroarginine methyl ester was reversed by L-arginine. Dexamethasone (which prevents the induction of type II NOS) also inhibited the LPS-dependent increase in [NOx] with ED50 values of 0.05 mg/kg (rat) and 1 mg/kg (mouse), but did not lead to decreased survival. Thus, inhibition of the type I (neuronal) or type III (endothelial) NOS, rather than the type II isoform, may be a possible mechanism for the animal mortality. These models provide a simple and reproducible means for assessing the in vivo inhibition of type II NOS by various compounds.

Efficacy of a fibrin hemostatic bandage in controlling hemorrhage from experimental arterial injuries.

Abstract: Objective: To determine if a pressure dressing containing fibrinogen and thrombin could provide more effective control of arterial hemorrhage than a pressure dressing alone in an animal model of arterial injury. Design: Randomized acute (nonsurvival) experiment in swine. Setting: Federal biomedical research institute. Animals: Six anesthetized Yorkshire swine. Interventions: Uncontrolled arterial hemorrhage was induced in anesthetized swine by creating femoral artery lacerations. Hemorrhage was controlled by a gauze bandage containing fibrinogen and thrombin, applied with 1 minute of 3.5-kg pressure. The dressings were left in place for 1 hour after the pressure was removed. The contralateral limbs received identical treatment with plain gauze dressings. Main Outcome Measures: Total blood loss, mean arterial pressure, and mortality were measured after 1 hour. Results: After 1 hour, blood loss in the fibrin bandage group was 123±48 mL, compared with 734±134 mL in the control group ( P =.0022). In the group treated with the fibrin bandages, there was no significant decrease in the mean arterial pressure after arterial laceration. In contrast, there was a decrease of 30 mm Hg in the group treated with gauze dressings alone. There was no animal mortality during the study period. Conclusions: Bandages containing fibrinogen and thrombin significantly reduced the amount of blood loss and allowed mean arterial pressures to be maintained in animals with uncontrolled hemorrhage from femoral artery lacerations. A hemostatic bandage may be an important adjuvant for controlling severe extremity hemorrhage in the prehospital setting. (Arch Surg. 1995;130:420-422)

Effect of surgical removal of subcutaneous tumors on survival of rats.

Abstract: Mammary and other subcutaneous tumors were surgically removed from aged Sprague-Dawley rats in an attempt to extend survival. The surgical technique was straightforward, and survival following mastectomy was good (17/21). The number of mammary and pituitary tumors in sexually intact rats and those that had previously undergone ovariectomy were compared. The frequency of mammary tumors was significantly lower in ovariectomized vs sexually intact rats (2/47 vs 24/49), as was the frequency of pituitary adenomas (2/46 vs 27/41). Survival to 630 days of age was higher in ovariectomized than in sexually intact rats (42/47 vs 29/49), although tumors did not contribute significantly to mortality.

Hyperinsulinemia inhibits hepatic peroxisomal beta-oxidation in rats.

Abstract: Studies show that insulin deficiency enhances peroxisomal enzyme activities. It is not known, however, whether hyperinsulinemia exerts the opposite effect on peroxisomes. Male Sprague-Dawley rats were infused with normal saline, glucose or galactose for 7 days. Only glucose caused an increase in serum insulin levels. The increase in insulin secretion, in response to glucose, was blocked with diazoxide. Data show an inverse relationship between serum insulin levels and hepatic peroxisomal beta-oxidation (r2 = 0.90, p < 0.01). While hyperinsulinemic rats had diminished peroxisomal beta-oxidation, lowering serum insulin restored peroxisomal enzyme activity to normal levels. These effects were independent of blood glucose levels (r2 = 0.35). In addition to decreasing peroxisomal beta-oxidation, hyperinsulinemia was accompanied by accelerated animal mortality, an effect which was also prevented by lowering serum insulin levels. Peroxisomal deficit may be a potentially lethal consequence of hyperinsulinemia.

Enhancement of liver size by stimulation of intact rat liver with exogenous hepatotrophic factors

Abstract: In mammals, liver size is related to animal body weight at the 2.5 to 3% proportion, a ratio mediated by the afflux of hepatotrophic factors. Formulas capable of modifying this ratio have been developed in previous studies on the rat, with enhancement of liver size brought about by intraperitoneal (portal) infusion of exogenous factors such as glucose, amino acids, insulin, glucagon, vitamins, electrolytes, and triiodothyronine. However, the efficacy of these formulations was accompanied by increased animal mortality (PARRA et al.19,20 ). The present study, which was carried out with small methodological modifications on a larger number of rats using daily intraperitoneal injections of a solution of exogenous hepatotrophic factors (40 ml/kg) for seven days, confirms the previous findings, with a 114.16 ± 7.90% enhancement of liver size beyond the expected value for the body weight of the animal. However, the problem of animal mortality was not fully resolved.

In vivo pharmacological evaluation of two novel type I1 (inducible) nitric oxide synthase inhibitors

Abstract: Selective type I1 (inducible) nitric oxide synthase (NOS) inhibitors have several potential therapeutic applications, including treatment of sepsis, diabetes, and autoimmune diseases. The ability of two novel, selective inhibitors of type 11 NOS, S-ethylisothiourea (EIT) and 2-amin0-5~6-dihydr0-6-methyl4H- B ,3-thiazine (AMT), to inhibit type I1 NOS function in vivo was studied in lipopolysaccharide (LPS) treated rats. Type I1 NOS activity was assessed by measuring changes in plasma nitrite and nitrate concentrations ((NO,)). Both EIT and AMT elicited a dose- dependent and >95% inhibition of the LPS-induced increase in plasma (NO,). The ED,, values for EIT and AMT were 0.4 and 0.2 mg/kg, respectively. In addition, the administration of LBS and either NOS inhibitor resulted in a dose-dependent increase in animal mortality; neither compound was lethal when administered alone. Pretreatment with L-arginine (but not D-arginine) prevented the mortality, while not affecting the type I1 NOS-dependent NO production, suggesting the toxicity may be due to inhibition of one of the other NOS isofoms (endothellial or neuronal). Thus, although EIT and AMT are potent inhibitors of type I1 NOS function in vivo, type I1 NOS inhibitors of even greater selectivity may need to be developed for therapeutic applications.