INTRODUCTION: One of the main causes of @entity204 in European and US intensive care units is @entity295 . It involves a network of pro-inflammatory cytokines such as @entity310 , @entity1356 and @entity650 . Furthermore, there is an up regulation of transcription factors such as @entity2451 . It has previously been shown that @entity1338 is able to significantly reduce pro-inflammatory cytokines in surgical @entity1 . We therefore hypothesise that the clinically used central alpha-2 agonist @entity1338 has the ability to improve survival in experimental @entity295 by inhibiting the sympathetic tone and consequently inhibiting the pro-inflammatory cytokine release. METHODS: To investigate this therapeutic potential of @entity1338 in a prospective randomised laboratory investigation we used a @entity19 model of caecal ligation and puncture ( @entity12147 ) induced @entity295 . Animals receiving pre-emptive injections were treated with either @entity1338 (5 microg/kg) or @entity6948 (40 microg/kg) 12 and 1 hours before the operation, as well as 1, 6 and 12 hours afterwards. Another group of animals only received @entity1338 (5 microg/kg) 1, 6 and 12 hours after the operation, while the pre-emptive injections were normal saline. The control groups received solvent injections at the respective time points. RESULTS: Pre-emptive administration of a central sympatholytic significantly reduced mortality ( @entity1338 : p = 0.015; @entity6948 : p = 0.029), although postoperative administration of @entity1338 failed to significantly prolong survival. Furthermore pre-emptive administration of @entity1338 significantly attenuated the cytokine response after @entity12147 -induced @entity295 ( @entity635 : p = 0.017; @entity777 : p < 0.0001; @entity637 : p < 0.0001), preserved blood pressure control (p = 0.024) and down-regulated the binding activity of NF-kappaB. There were no changes in the pro-inflammatory cytokine response when peripheral blood was incubated with lipopolysaccharide alone compared with incubation with @entity1338 (10-4 M) plus @entity558 (p > 0.05). CONCLUSIONS: Our results demonstrate that the pre-emptive administration of either @entity1338 or @entity6948 have the ability to successfully improve survival in experimental @entity295 . Furthermore, there seems to be a connection between the central muscarinic network and the vagal cholinergic response. By down-regulating pro-inflammatory mediators sympatholytics may be a useful adjunct sedative in @entity1 with a high risk for developing @entity295 .

Central sympatholytics prolong survival in experimental XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity558 :: ('MESH:C536528', 'Disease') :: ['LPS'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis'] @entity2451 :: ('4790', 'Gene') :: ['nuclear factor (NF) kappaB'] @entity1356 :: ('3553', 'Gene') :: ['IL-1beta'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['mIL-1beta'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['mIL-6'] @entity12147 :: ('12950(Tax:10090)', 'Gene') :: ['CLP'] @entity1338 :: ('MESH:D003000', 'Chemical') :: ['clonidine'] @entity6948 :: ('MESH:D020927', 'Chemical') :: ['dexmedetomidine'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['mTNF-alpha']
@entity295 :: (MESH:D018805,Disease) :: ['sepsis']
