TY - JOUR
T1 - Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats
AU - Yang, Chih Lin
AU - Chen, Cay Huyen
AU - Tsai, Pei Shan
AU - Wang, Tao Yeuan
AU - Huang, Chun-Jen
N1 - Funding Information:
The authors acknowledge support for this work by a grant from the National Science Council , Taiwan ( NSC 96-2314-B-195-004-MY3 ) awarded to C-J H.
PY - 2011/5/15
Y1 - 2011/5/15
N2 - 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. Materials and 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.
AB - 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. Materials and 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.
KW - chemokine
KW - cyclooxygenase 2
KW - cytokine
KW - high-tidal volume ventilation
KW - inducible nitric oxide synthase
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U2 - 10.1016/j.jss.2010.02.020
DO - 10.1016/j.jss.2010.02.020
M3 - Article
C2 - 20452617
AN - SCOPUS:79954591061
SN - 0022-4804
VL - 167
SP - e273-e281
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -