Dexmedetomidine regulates inflammatory molecules contributing to ventilator-induced lung injury in dogs.

Abstract

BACKGROUND:

Dexmedetomidine reduced mortality and inhibited the inflammatory response during endotoxemia in rats. The aim of this study was to clarify the effect of dexmedetomidine-regulating inflammation on a noninfectious, ventilator-induced lung injury (VILI) in dogs.

METHODS:

Thirty healthy Beagles weighing between 8 and 12 kg were randomly divided into five groups: control group (group C, n = 6), mechanical ventilation (group MV, n = 6), and three different doses of dexmedetomidine group (group DEX1-3, n = 6). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 15 breaths/min; FiO2 0.5). Group DEX received intravenous Dex 20 min before endotracheal intubation (0.5, 1.0, and 2.0 μg/kg Dex was infused within 20 min and then a maintenance dose of 0.5, 1.0, and 2.0 μg/kg/h Dex was infused intravenously). Arterial blood samples were obtained from femoral artery at base state, MV1h, MV2h, and MV4h for blood gas analysis. After being mechanically ventilated for 4 h, dogs were killed and the levels of pulmonary inflammatory response and polymorphonuclear neutrophils (PMNs) count in bronchoalveolar lavage fluid were evaluated.

RESULTS:

Histologic findings of the MV, DEX1, DEX2, and DEX3 groups revealed severe, moderate, mild, and normal to minimal inflammation, respectively. Myeloperoxidase level, PMNs/alveoli ratio, nuclear factor-κB messenger RNA (mRNA), tumor necrosis factor-alpha mRNA, and inducible nitric oxide synthase mRNA expression in lung tissues of the DEX2 and DEX3 were significantly lower than those of the MV group. Partial pressures of oxygen was decreased significantly at MV4h as compared with the baseline. There was no statistical significance in partial pressures of oxygen between MV and DEX2 group as well as between group MV and group DEX3.

CONCLUSIONS:

Dexmedetomidine could mitigate pulmonary inflammatory response induced by VILI in dogs.

• Authors: Chang Chen, Zongze Zhang, Kai Chen, Fan Zhang, Mian Peng, Yanlin Wang
• Journal: The Journal of surgical research (J Surg Res) Vol. 187 Issue 1 Pg. 211-8 (Mar 2014) ISSN: 1095-8673 [Electronic] United States
• PMID: 24209806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Dexmedetomidine
• Peroxidase
• Nitric Oxide Synthase Type II

Topics

• Adrenergic alpha-2 Receptor Agonists (pharmacology)
• Animals
• Blood Gas Analysis
• Dexmedetomidine (pharmacology)
• Disease Models, Animal
• Dogs
• Lung (drug effects, immunology, pathology)
• NF-kappa B (metabolism)
• Neutrophils (drug effects, immunology)
• Nitric Oxide Synthase Type II (metabolism)
• Organ Size
• Peroxidase (metabolism)
• Random Allocation
• Respiration, Artificial (adverse effects)
• Tumor Necrosis Factor-alpha (metabolism)
• Ventilator-Induced Lung Injury (drug therapy, immunology, pathology)