Hofer, Stefan and Steppan, Jochen and Wagner, Tanja and Funke, Benjamin and Lichtenstern, Christoph and Martin, Eike and Graf, Bernhard M. and Bierhaus, Angelika and Weigand, Markus A. (2009) Central sympatholytics prolong survival in experimental sepsis. CRITICAL CARE, 13 (1): R11. ISSN 1466-609X, 1364-8535
Full text not available from this repository. (Request a copy)Abstract
Introduction One of the main causes of death in European and US intensive care units is sepsis. It involves a network of pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6. Furthermore, there is an up regulation of transcription factors such as nuclear factor (NF) kappa B. It has previously been shown that clonidine is able to significantly reduce pro-inflammatory cytokines in surgical patients. We therefore hypothesise that the clinically used central alpha-2 agonist clonidine has the ability to improve survival in experimental sepsis by inhibiting the sympathetic tone and consequently inhibiting the pro-inflammatory cytokine release. Methods To investigate this therapeutic potential of clonidine in a prospective randomised laboratory investigation we used a murine model of caecal ligation and puncture (CLP) induced sepsis. Animals receiving pre-emptive injections were treated with either clonidine (5 mu g/kg) or dexmedetomidine (40 mu g/kg) 12 and 1 hours before the operation, as well as 1, 6 and 12 hours afterwards. Another group of animals only received clonidine (5 mu g/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 (clonidine: p = 0.015; dexmedetomidine: p = 0.029), although postoperative administration of clonidine failed to significantly prolong survival. Furthermore pre-emptive administration of clonidine significantly attenuated the cytokine response after CLP-induced sepsis (mIL-1beta: p = 0.017; mIL-6: p < 0.0001; mTNF-alpha: p < 0.0001), preserved blood pressure control (p = 0.024) and down-regulated the binding activity of NF-kappa B. There were no changes in the pro-inflammatory cytokine response when peripheral blood was incubated with lipopolysaccharide alone compared with incubation with clonidine (10(-4) M) plus LPS (p > 0.05). Conclusions Our results demonstrate that the pre-emptive administration of either clonidine or dexmedetomidine have the ability to successfully improve survival in experimental sepsis. 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 patients with a high risk for developing sepsis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; SEPTIC SHOCK; INFLAMMATION; PERITONITIS; RECEPTORS; CLONIDINE; ENDOTOXIN; SEDATION; MEDIATOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Oct 2020 07:04 |
| Last Modified: | 12 Oct 2020 07:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29699 |
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