Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats.
BACKGROUND
Pulmonary inflammatory response is crucial in mediating the development of ventilator-induced lung injury (VILI) in animals experiencing endotoxemia. Dexmedetomidine and ketamine are two sedative agents with potent anti-inflammatory capacity. We sought to elucidate the anti-inflammatory effects of dexmedetomidine-ketamine combination against VILI in endotoxemia rats.


METHODS
Eighty-four adult male rats were allocated to receive normal saline, VILI, VILI plus dexmedetomidine-ketamine combination (D+K), lipopolysaccharide (LPS), LPS plus D+K, LPS plus VILI, or LPS plus VILI plus D+K (designated as the NS, V, V-D+K, LPS, LPS-D+K, LPS/V, and LPS/V-D+K group, respectively; n = 12 in each group). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 50 breath/min; FiO(2) 21%). After being mechanically ventilated for 4 h, rats were sacrificed and the levels of pulmonary inflammatory response were evaluated.


RESULTS
Histologic findings revealed severe, moderate, and mild inflammation in lung tissues of the LPS/V, LPS, and V groups, respectively, whereas those of the LPS/V-D+K, LPS-D+K, and V-D+K groups revealed moderate, mild, and normal to minimal inflammation, respectively. Moreover, the total cell number and the concentrations of macrophage inflammatory protein-2 and interleukin-1β in bronchoalveolar lavage fluid as well as the lung water content, leukocyte infiltration, myeloperoxidase activity, and the concentrations of inducible nitric oxide synthase/nitric oxide, and cyclooxygenase 2/prostaglandin E(2) in lung tissues of the LPS/V, LPS, and V groups were significantly higher than those of the LPS/V-D+K, LPS-D+K, and V-D+K groups, respectively.


CONCLUSIONS
Dexmedetomidine-ketamine combination could mitigate pulmonary inflammatory response induced by VILI in endotoxemia rats.
Yang
Chih-Lin
CL
Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan.
Chen
Cay-Huyen
CH
Tsai
Pei-Shan
PS
Wang
Tao-Yeuan
TY
Huang
Chun-Jen
CJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D020927:Dexmedetomidine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D019446:Endotoxemia / Q000150:complications*; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D007962:Leukocytes / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012122:Ventilators, Mechanical / Q000009:adverse effects*
D000893:Anti-Inflammatory Agents; D006993:Hypnotics and Sedatives; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D020927:Dexmedetomidine; D007649:Ketamine; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II