Dragan Djurdjevic

Effects of different anesthetic agents on GM-CSF, MCP1, IL1α and TNFα levels in rat sepsis model.

Anesthetic agents could alter the course and outcome of physical trauma, as well as experimentally or naturally occurring severe infections, by regulating several immune response mechanisms. The aim of our study was to investigate the influence of several commercially used anesthetic agents (ketamine, propofole, pentylentetrazole - PTZ) on cytokine concentrations, animal survival and pathohistological changes in the model of rat sepsis. In adult, male Wistar rats after different anesthetic treatment and induction of sepsis by cecal ligation and punction we estimated serum levels of IL1α, TNFα, GM-CSF and MCP-1 at 12h intervals. After 48h of sepsis induction, the largest number of animals survived in the group treated with PTZ (47%), while the lowest survival rate was in the propofole treatment group (24%). Contrary to survival rate, the most abundant pathohistological changes were seen on preparations from PTZ and than in ketamine/PTZ treated groups, without any significant changes in the CNS of propofole treated animals. In the propofole treated group there was a prominent increament of GM-CSF values at 12h and 24h, followed by a significant decreament at 36h. These changes were negatively correlated to the survival rate in this group. This group had the lowest levels of MCP1 at all evaluated time intervals. After high initial levels, IL1α and TNFα levels fell to undetectable concentrations and at 24h increased to a high level. In PTZ as well as ketamine groups, at 12 h interval, GM-CSF levels were lower than in the propofole treated group. Contrary, MCP-1 levels were higher in these groups comparing to propofole group. After a high initial peak, IL1α levels decreased to low but detectable levels, followed by an intensive rise in ketamine treated, but with further decrement in pentazole treated groups. TNFα levels were low through all evaluated intervals in both these groups. Our results indicate that induction of anaesthesia of animals with sepsis with variuos anesthetic agents is connected to different pathohistological CNS changes, distinct serum cytokine profiles and diverse survival rates.

The effect of physostigmine on the haemorrhagic hypovolemia in anaesthetized rabbits

1. The effects of physostigmine (70 micrograms kg-1, intravenously) on mean arterial blood pressure, blood volume and survival were studied in anaesthetized rabbits subjected to haemorrhagic hypovolemia. 2. It was found that physostigmine increased the mean arterial blood pressure, increased the residual blood volume, decreased the haematocrit values and increased the survival of the animals. 3. The increase of blood pressure might be due to a general adrenergic activation produced by physostigmine, whereas the increase in plasma volume might be due to changes in pre- to postcapillary resistance ratio. 4. The beneficial effect of physostigmine might also be due to antagonism of humoral factors known to aggravate the hypovolemia (e.g. endogenous opioids).

Disulfiram moderately restores impaired hepatic redox status of rats subchronically exposed to cadmium

Abstract Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1 mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O2·−) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact. Graphical Abstract