LPS was dissolved in 0.5 ml 0.9% sodium chloride (NaCl). LPS was given within two to three minutes. The control group received 0.5 ml vehicle. A moderate volume therapy selleck catalog of 1 to 6 ml/kg/h 0.9% NaCl was allowed in all groups. Thirty minutes after sepsis induction 1400W was given as a bolus of 7.5 mg/kg followed by a continuous infusion at a rate of 7.5 mg/kg/h. NE was given in doses between 0.01 and 10 ��g/kg/min to stabilize mean blood pressure in the lower physiologic range between 90 and 100 mmHg.Prior to and then after LPS administration SEPs, evoked and resting cerebral blood flow velocity levels and blood pressure were measured up to 270 minutes.In an additional group (n = 3), we investigated the effects of the same dose of 1400W without sepsis induction in healthy rats.

StatisticsIf appropriate, a two-way analysis of variance was performed to assess differences within and between groups. In case of significance a Fischer post-hoc test was applied. If assumptions of normal distribution and equality of variances could not be assured, a nonparametric Friedman test was undertaken instead (Statview, SAS, Cary, NA, USA). The significance level was set to P < 0.05.ResultsNo rat died from LPS injection. Table Table11 shows the group averaged data for partial pressure of carbon dioxide, pH, glucose, lactate, and hemoglobin content. Partial pressure of oxygen levels remained in the range of 240 to 250 mmHg in all groups throughout experiments and therefore were not specified in the table.

Table Table22 indicates the group data for blood pressure together with the resting LDF signal, N2-P1 potential amplitude, P1 latency, and evoked flow velocity response. The cytokines as well as the cell destruction markers are given in Table Table33.Table 1Group averaged data for glucose, lactate, pH, pCO2 and hemoglobin for all groupsTable 2Group averaged data for mean blood pressure, somatosensory evoked potentials, P1 latencies, evoked flow velocity responses, and resting LDFV signal, for the different time points of the experimentTable 3Data from cytokine and destruction marker measurements as group averaged data �� standard deviationIn non-septic rats, 1400W did not result in changes in the following data: blood pressure (121 �� 11 vs.125 �� 6 mmHg; not significant), glucose levels (60 �� 9 vs.57 �� 6 mmol/L; not significant), resting cerebral blood flow (135 �� 25 vs.

142 �� 28; not significant), evoked flow responses (20 �� 7 vs. 20 �� 8%; not significant), SEP amplitudes (16 �� 6 vs.15 �� 4 ��V; not significant), or P1-latencies (10 �� 2 vs.10 �� 1 ms; not significant).General findingsWith LPS-administration, rats developed signs of a severe sepsis syndrome characterized by a considerable drop in blood pressure (1 mg/kg LPS: 63 �� 10 Anacetrapib mmHg; 5 mg/kg LPS: 56 �� 11 mmHg), occurrence of metabolic acidosis (1 mg/kg LPS: 7.48 �� 0.04; 5 mg/kg LPS: 7.46 �� 0.