Central sympatholytics prolong survival in experimental sepsis

Hofer, Stefan; Steppan, Jochen; Wagner, Tanja; Funke, Benjamin; Lichtenstern, Christoph; Martin, Eike; Graf, Bernhard M.; Bierhaus, Angelika; Weigand, Markus A.

doi:10.1186/cc7709

Cited by 108 publications

(91 citation statements)

References 29 publications

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“…Some clinical investigations have suggested the potential significance of IL-6 as a prognostic factor in patients with gastric cancer [42,43]. Studies have also found that dexmedetomidine has a significant anti-inflammatory effect against endotoxin-induced inflammation [17,28,44]. Studies suggested the anti-inflammatory effect of dexmedetomidine could be resulted by reducing the serum levels of inflammatory cytokines [44e51].…”

Section: Discussionmentioning

confidence: 99%

Effects of dexmedetomidine on patients undergoing radical gastrectomy

Wang

Liu

et al. 2015

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 99%

Effects of dexmedetomidine on patients undergoing radical gastrectomy

Wang

Liu

et al. 2015

Journal of Surgical Research

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“…Although this study investigated the differential effects of indomethacin on renal and cardiac SNA in sepsis, the effects on other sympathetic nerves, such as those innervating muscle, gut, and spleen, remain to be determined. It also remains to be determined whether selectively reducing the increase in CSNA early in sepsis is associated with improved outcome in hyperdynamic sepsis; however, this is supported by the finding that central sympatholytics and ␤-blockers have beneficial effects in human and experimental sepsis (1,6,13,19,33).…”

Section: Perspectives and Significancementioning

confidence: 77%

“…These changes are accompanied by activation of the sympathetic nervous system, as demonstrated by increased circulating levels of plasma catecholamines in septic humans (12), increased renal sympathetic nerve activity (RSNA) in endotoxemic rats (22,30), and increased SNA to the heart and kidneys in sheep with hyperdynamic sepsis (24). It would be expected that an increase in SNA would be beneficial in sepsis, for example, by maintaining arterial pressure; however there is recent evidence that sympatholytic agents have beneficial actions in experimental sepsis in rodents (1,6,13,33). It is, therefore important to identify the mechanisms leading to the organ-selective increase in SNA in sepsis, as this may lead to development of more targeted treatments.…”

mentioning

confidence: 99%

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

Booth

Ramchandra

Calzavacca

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Booth LC, Ramchandra R, Calzavacca P, May CN. Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis. Am J Physiol Regul Integr Comp Physiol 307: R75-R81, 2014. First published April 30, 2014 doi:10.1152/ajpregu.00450.2013.-Effective treatment of sepsis remains a significant challenge in intensive care units. During sepsis, there is widespread activation of the sympathetic nervous system, which is thought to have both beneficial and detrimental effects. The sympathoexcitation is thought to be partly due to the developing hypotension, but may also be a response to the inflammatory mediators released. Thus, we investigated whether intracarotid infusion of prostaglandin E2 (PGE2) induced similar cardiovascular changes to those caused by intravenous infusion of Escherichia coli in sheep and whether inhibition of prostaglandin synthesis, with the nonselective cyclooxygenase inhibitor indomethacin, administered at 2 and 8 h after the onset of sepsis, reduced sympathetic nerve activity (SNA), and heart rate (HR). Studies were performed in conscious sheep instrumented to measure mean arterial pressure (MAP), HR, cardiac SNA (CSNA), and renal SNA (RSNA). Intracarotid infusion of PGE2 (50 ng·kg Ϫ1 ·min Ϫ1 ) increased temperature, CSNA, and HR, but not MAP or RSNA. Sepsis, induced by infusion of E. coli, increased CSNA, but caused an initial, transient inhibition of RSNA. At 2 h of sepsis, indomethacin (1.25 mg/kg bolus) increased MAP and caused reflex decreases in HR and CSNA. After 8 h of sepsis, indomethacin did not alter MAP, but reduced CSNA and HR, without altering baroreflex control. These findings indicate an important role for prostaglandins in mediating the increase in CSNA and HR during the development of hyperdynamic sepsis, whereas prostaglandins do not have a major role in determining the early changes in RSNA.sepsis; cardiac sympathetic nerve activity; renal sympathetic nerve activity; PGE2; indomethacin; baroreflex curve; sheep SEPSIS AND SEPTIC SHOCK ARE the chief causes of death in intensive care units with mortality rates of between 30 and 70% when combined with multiorgan failure (2, 20, 21, 28). Although the incidence of sepsis is increasing, our knowledge of the pathology is limited, and current treatments, including volume resuscitation and vasoconstrictors, are only marginally effective. In human septic patients the most common hemodynamic profile is a hyperdynamic circulation, characterized by peripheral vasodilatation and hypotension accompanied by an increased cardiac output (16,17). These changes are accompanied by activation of the sympathetic nervous system, as demonstrated by increased circulating levels of plasma catecholamines in septic humans (12), increased renal sympathetic nerve activity (RSNA) in endotoxemic rats (22,30), and increased SNA to the heart and kidneys in sheep with hyperdynamic sepsis (24). It would be expected that an increase in SNA would be beneficial in sepsis, for example, by maintaining arterial pressure; however there...

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“…Dexmedetomindine is used in order to inhibit sympathetic nerve activity, and further sedation, analgesia, antianxiety and other effects (15). Some previous studies reported that dexmedetomidine could inhibit the infl ammatory reaction by blocking the cascade reaction (16)(17)(18). In those studies, dexmedetomidine was shown to improve infl ammation by depressing the expression of IL-1β, and TNF-α which promote cell apoptosis (19,20).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine protected COPD-induced lung injury by regulating miRNA-146a

Li¹,

Ouyang²,

Liu³

et al. 2016

BLL

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OBJECTIVE: To study the mechanism of protection provided by dexmedetomidine against COPD-induced lung injury. METHODS: COPD rat model was determined by measuring lung function, and comparing HE staining between two different groups. We got the lung tissue and cells from the control and COPD groups. The cells were divided into three groups: control group, and blank and drug groups that were from the COPD rats. Cell apoptosis, relative gene expression and TNF-α and IL-1β from nutrient solution were measured. Chronic obstructive pulmonary disease (COPD) is a kind of main damage located in airways and lung tissue, causing systemic disease progressively affecting other tissues and organs The symptoms are not reversible. Clinical research shows that the incidence of hospitalized patients with chronic pulmonary disease gradually increases (1). In 2040, COPD will become the world's most endangering disease (2, 3). COPD pathogenesis is not yet entirely clear, but the current study showed that the main causes of COPD include protease/anti-protease imbalance, oxidant/antioxidant imbalance stress (4-7), infl ammatory/anti-infl ammatory response imbalance (8), mechanical stretch injury (9), etc. Clinical treatment is often used for the purpose of mechanical ventilation after induction of anesthesia. Dexmedetomidine is a highly selective α2-adrenergic receptor agonist (10); it not only can effectively calm, but also has some anti-infl ammatory effect (11). However, the mechanism of dexmedetomidine protection against COPD is unclear. The objective of the present study is to explain the latter mechanism. Material and method Animals and cigarette smoke exposureIn our study, we used 6-week-old SD rats at body weight 110±20 g from the animal center, Nanfang Hospital of Southern Medical University. Before the experiment, the rats were accommodated for seven days. All procedures were in compliance with the institutional and national guidelines for the care and use of laboratory animals. The Study Protocol was approved by The Institutional Animal Care and Use Committee, Hebei Medical University. Rats were randomized into two groups: Control Group (n = 8) and Smoking Group (n = 16). The rats in smoking group were exposed to cigarette smoke in a smoking device manufactured by Shijiazhuang Jinyang Science and Technology Inc. (model: JY-01, Shijiazhuang, Hebei, China). Briefl y, 20 cigarettes were burnt continuously and blown into a box together with oxygen, while the whole bodies of animals were exposed to the cigarette smoke in the box. Animals were exposed to cigarette smoke for one hour each time, twice a day, 5 days a week for 16 weeks. After 16 weeks, the rats were analyzed for relative index of COPD including tidal volume (TV), peak expiratory fl ow (PEF), 50 % exhaled tidal volume during expiratory fl ow rate (EF50), forced expiratory volume in 0.3 seconds (FEV0.3) and FEV0.3/ forced vital capacity (FVC). Tissues and cellThe rats were sacrifi ced by femoral artery bleeding. Lung tissue was extracted and a proportion was ...

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Central sympatholytics prolong survival in experimental sepsis

Cited by 108 publications

References 29 publications

Effects of dexmedetomidine on patients undergoing radical gastrectomy

Effects of dexmedetomidine on patients undergoing radical gastrectomy

Role of prostaglandins in determining the increased cardiac sympathetic nerve activity in ovine sepsis

Dexmedetomidine protected COPD-induced lung injury by regulating miRNA-146a

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