Abstract

Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague–Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation.

Highlights

  • Pain and anxiety are common in critically ill due to intubation, infection, trauma and longterm bedridden

  • In the PF group, no significant difference in body weight, extensor digitorum longus (EDL) weight and EDL–BW ratio were observed when compared with the control, indicating that the decreased food intake had very little effect on muscle weight

  • Original data can be seen in S1 Tables

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Summary

Introduction

Pain and anxiety are common in critically ill due to intubation, infection, trauma and longterm bedridden. Benzodiazepines have been reported to be associated with increased risk of delirium, coma and respiratory depression[4]. Dexmedetomidine, a new sedative, can cause analgesia and induce a sedative state similar to physiologic sleep without causing respiratory depression, by acting on α-2 receptors in the locus caeruleus[6]. Besides the benefits of shortening duration of mechanical ventilation and length of ICU stay, dexmedetomidine has been demonstrated to reduce risk of delirium and hypertension[7,8]. In our previous study, we found that the addition of dexmedetomidine to analgesia for patients after abdominal operations could enhance recovery of gastrointestinal function, alleviate postoperative pain and lower metabolism[9]. The exact mechanism of these positive effecets on critically ill is still unkown

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