Intervention with nitric oxide synthase inhibitors for traumatic shock in rats.

OBJECTIVE: To evaluate the effects of a selective inhibitor of inducible nitric oxide synthase (iNOS) aminoguanidine (AG) and a non-selective inhibitor of nitric oxide synthase (NOS) N(G)-nitro-L-arginine methylester (L-NAME) on traumatic shock in rats. METHODS: Animal models of traumatic shock were established in 44 Sprague-Dawley rats following fractures in both femur shafts and subsequent depletion until the mean arterial pressure in the femoral artery dropped to 35 to 45 mmHg(4.67-6.00 kPa). Hypotension was maintained for 30 min before the collected blood was infused back into the rats supplemented with Ringer's solution of the same volume. The rat models were then randomly divided into 3 groups, namely traumatic shock group (n=10), AG group (which was subdivided into AGI, AGII, and AGIII groups, each consisting of 8 rats and receiving 2, 8, and 60 mg/kg x b.w AG infusion respectively during resuscitation), and L-NAME group (with 8 mg/kg x b.w L-NAME infusion during resuscitation, n=10). Plasma NO levels were determined before and after shock, immediately after resuscitation and 0.5, 2, 4 h after resuscitation, and the survival rates within 24 h were recorded with tissue samples of the lung, liver, kidney and intestine obtained 24 h after shock for microscopic examination. RESULTS: Plasma NO level was seen to increase markedly after traumatic shock in the rat models. In the 3 AG groups, the elevated NO levels following the shock were obviously reduced after resuscitation with less tissue damages and higher survival rates, as compared with the other 2 groups. The best protective effect against traumatic shock was observed in AGIII group. In spite of obvious plasma NO level-lowering effect after resuscitation, L-NAME exhibited little efficacy in alleviating the tissue damages in the organs and hence failed to improve the survival rate of the rats. CONCLUSIONS: NO plays an important role in the pathological process of traumatic shock, and the application of AG may improve the condition. L-NAME can decrease plasma NO level after resuscitation, but fail to improve the outcome of traumatic shock in rats.

Deficiency in peripheral glutamine production in pediatric patients with burns.

Plasma glutamine levels decrease in association with severe injury, which suggests that the consumption of glutamine exceeds the production of glutamine or possibly represents a deficit in the release of glutamine from skeletal muscle. The goal of this study was to assess the peripheral glutamine kinetic response to prolonged stress in children with critical injuries. To accomplish this purpose, we quantitated peripheral glutamine kinetics in vivo with the use of 5N15 glutamine in 5 children with severe burns (total body surface area, 74%+/-14%; mean +/- SEM) and 3 children who underwent elective scar reconstruction. In the children with severe burns, leg blood flow was significantly elevated (16.2+/-2.1 vs 7.5 +/-0.3 mL/min/100 mL leg volume, P < .02) and the arterial concentration of glutamine was significantly reduced (0.31+/-0.04 vs 0.84+/-0.05 mmol/L, P < .001). The rate of glutamine turnover within the leg was significantly reduced in the patients with acute burns, whereas the net efflux of glutamine was similar between the 2 groups. These findings suggest that plasma glutamine concentrations decrease during severe stress as a result of a deficit in peripheral glutamine release in conjunction with an increased central consumption. This preliminary study supports the notion that exogenous glutamine supplementation in pediatric patients with severe injuries may be needed because of this inadequate skeletal muscle response.

[Effect of acupuncture on the contents of enkephalins in different brain regions of rats with traumatic shock].

The study was carried out on the animal model of traumatic shock which induced by ligating bilateral hind legs. The contents of enkephalins in hippocampus, striatum, hypothalamus, diencephalon and brain stem were determined with radioimmunoassay. The results show that: (1) when traumatic shock occurs, the contents of Met-enkephalin are not obvious change in the above 5 brain regions, and also not significant change after acupuncture; (2) there is a tendency to increase the content of Leu-enkephalin in each brain region described above of shock animal, while it is decreased in hypothalamus after acupuncture. The result suggests that the occurrence of traumatic shock may be related to the functional activities of Leu-enkephalinergic system in the central nervous system; the anti-shock of acupuncture may be through a decrease in the level of central Leu-enkephalin to improve micro-circulation and raise the blood pressure.

[Mechanisms of the beneficial effect of indomethacin and nimodipine in the treatment of traumatic shock in rats]. / Mehanizmi povoljnog efekta indometacina i nimodipina u lecenju traumatskog soka kod pacova.

Aiming to study the pathogenetic mechanisms of the disturbed function of the central nervous system in traumatic shock we have determined the dynamics of changes of eicosanoids (PGF2 alpha, TxB2, 6-keto-PGF1 alpha, peptidoleukotrienes) in the brain structures (medulla oblongata, hypothalamus) of the experimental animals subjected to bilateral trauma of the hind legs (tourniquet trauma, LD50). Considering that our previous data have shown the importance of eicosanoid mediatory system in the pathogenetic mechanisms of shock, we have studied possible use of prostaglandin synthesis inhibitors (indomethacin) and calcium channel antagonists (nimidipine) in traumatic shock. The authors have concluded that in the pathogenetic mechanism of the disturbed function of the CNS in traumatic shock the important role has peptidoleukotrienes as well as that the combined use of prostaglandin synthesis inhibitors and antagonists of voltage-dependent calcium channel would be useful in the therapy of the injured patients.

[Lipid peroxidation and the phospholipid composition of the liver plasma membranes in rabbits in traumatic shock and their pharmacological correction]. / Perekisnoe okislenie lipidov i fosfolipidnyi sostav plazmaticheskikh membran pecheni krolikov pri travmaticheskom shoke i ikh farmakologicheskaia korrektsiia.

Changes in peroxidation of hepatic tissue lipids were studied in experiments on rabbits with Cannon's traumatic shock according to products reacting with thiobarbituric acid. The lipid composition of hepatocyte plasma membranes was studied by thin-layer chromatography. The levels of lipid peroxidation products and the ratio of phospholipid fractions changed depending on the stage of the process. Administration of superoxide dismutase in the initial periods of shock reduced the raised level of products reacting with thiobarbituric acid and maintained the ratio of phospholipid fractions in the hepatocyte plasma membrane at the initial level.

[Effect of cytochrome c on bioenergetic processes in the liver in severe compression trauma]. / Vliianie tsitokhroma c na bioénergeticheskie protsessy v pecheni pri tiazheloi kompressionnoi travme.

After severe mechanical trauma of rat soft tissue content of ATP, total adenine nucleotides, amounts of "energy charge" of the adenine nucleotide system and cytochrome c were decreased in liver tissue, while content of AMP and Pi was increased. Parenteral administration of cytochrome c at a dose of 10 mg/kg into animals after the trauma normalized the energy processes in liver tissue and increased the content of endogenous cytochrome c.

[Changes in the met- and leu-enkephalin levels in the rat brain during burn shock]. / Izmeneniia soderzhaniia met- i lei-énkefalinov v strukturakh mozga krys pri ozhogovom shoke.

The dynamics of met-and leu-enkephalin content in the brain cortex and hypothalamus of rats with severe burn shock caused by 50% burns by boiling water were studied. A tendency towards burn-induced growth in leu-enkephalin hypothalamus level was observed, with the content of met-and leu-enkephalins in the hypothalamus significantly increasing 30 min later. Met-enkephalin content in the brain cortex also rises. 2 hours later the changes are less pronounced, with met-enkephalin hypothalamus level remaining elevated. The adaptive nature of changes, mobilization of endogenous anti-pain defensive mechanisms in severe burn shock and the role of hypothalamus structures in this process are suggested.

Studies on the mechanism of shock. Central serotoninergic neuron activity after trauma in the rat.

An attempt has been made to assess the effect of injury (limb ischaemia, scald) on the central serotoninergic system of the rat by studying the effect of these injuries on the tryptophan concentration, the tryptophan hydroxylase activity and the metabolism of serotonin in the hypothalamus, mid-brain and hind-brain. The effects of a serotonin uptake inhibitor and an antagonist on the survival time and mortality rate after limb ischaemia have been examined as well as the effects of central lesions produced by the injection of 5.6- and 5.7-dihydroxytryptamine into a lateral cerebral ventricle and the i.p. injection of (+/-)-4-chloroamphetamine. A few changes indicative of increased activity in the central serotoninergic system were found--an increase in tryptophan hydroxylase activity after 4 h bilateral hind-limb ischaemia, better survival of fed rats pre-treated with 5,6-dihydroxytryptamine--but for the most part the changes were not as great as those produced by starving or exposure to cold. Hence the effect of trauma on this system seems small.