Effects of dexmedetomidine on regulating pulmonary inflammation in a rat model of ventilator-induced lung injury

Chih Lin Yang, Pei Shan Tsai, Chun Jen Huang

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42 Citations (Scopus)

Abstract

Background: We sought to elucidate the effects of dexmedetomidine, a selective α2-adrenergic receptor agonist, on the regulation of pulmonary inflammation in ventilator-induced lung injury (VILI) in a rat model. Methods: A total of 64 adult male Sprague-Dawley rats were assigned to receive either standard ventilation (tidal volume 10mL/kg; respiratory rate 50 breaths/minute), high-tidal volume ventilation (HVT: tidal volume 20mL/kg; respiratory rate 50 breaths/minute), HVT plus dexmedetomidine (0.5, 2.5 or 5.0 μg/kg per hour), or HVT plus dexmedetomidine (0.5, 2.5 or 5.0 μg/kg per hour) and yohimbine (the α2-adrenergic receptor antagonist) (n=8 in each group). The doses of dexmedetomidine were chosen to correspond to 1, 5 and 10 times the clinical dose (0.5 μg/kg per hour). After maintaining ventilation for 4 hours, rats were sacrificed and pulmonary inflammatory changes as well as the upregulation of pulmonary inflammatory molecules were evaluated. Results: Histological and arterial blood gas analyses confirmed that HVT induced significant lung injury. HVT also significantly increased the pulmonary concentrations of chemokines (e.g. macrophage inflammatory protein-2), cytokines (e.g. tumor necrosis factor-α, interleukin [IL]-1β, and IL-6), inducible nitric oxide synthase/nitric oxide, cyclooxygenase-2/prostaglandin E2. Dexmedetomidine at the dose of 5.0 μg/kg per hour, but not at 0.5 and 2.5 μg/kg per hour, significantly attenuated the effects of HVT. Moreover, these effects of dexmedetomidine were significantly attenuated by yohimbine. Conclusion: Dexmedetomidine at clinically relevant doses had no significant effect in attenuating VILI. In contrast, dexmedetomidine at a dose approximately 10 times higher than the clinical dose significantly attenuated VILI. These effects of dexmedetomidine were mediated, at least in part, by the α2-adrenergic receptor.

Original languageEnglish
Pages (from-to)151-159
Number of pages9
JournalActa Anaesthesiologica Taiwanica
Volume46
Issue number4
DOIs
Publication statusPublished - Dec 2008

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Keywords

  • Cyclooxygenase2
  • Cytokines
  • Nitric oxide synthase type II

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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