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

《Acta Anaesthesiologica Taiwanica》 46卷4期 (2008/12) Pp. 151-159

並列摘要

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 (HV(subscript t): tidal volume 20mL/kg; respiratory rate 50 breaths/minute), HV(subscript t) plus dexmedetomidine (0.5, 2.5 or 5.0μg/kg per hour), or HV(subscript T) plus dexmedetomidine (0.5, 2.5 or 5.0μg/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 (0.5μg/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 HV(subscript T) induced significant lung injury. HV(subscript T) 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 5.0μg/kg per hour, but not at 0.5 and 2.5μg/kg per hour, significantly attenuated the effects of HV(subscript T). 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.

並列關鍵字

cyclooxygenase 2 ； cytokines ； nitric oxide synthase type II ； respiration, artificial