Dexmedetomidine-ketamine combination mitigates acute lung injury in haemorrhagic shock rats.
OBJECTIVE
Upregulation of pulmonary inflammatory molecules is crucial in mediating the development of acute lung injury induced by haemorrhagic shock. Dexmedetomidine and ketamine possess potent anti-inflammatory capacity. We sought to elucidate whether dexmedetomidine, ketamine, or dexmedetomidine-ketamine combination could mitigate acute lung injury in haemorrhagic shock rats.


METHODS
Fifty adult male Sprague-Dawley rats were randomized to the sham-instrumented, haemorrhagic shock (HS), HS plus dexmedetomidine (HS-D), HS plus ketamine (HS-K), or HS plus dexmedetomidine-ketamine (HS-D+K) group (n=10 in each group). Haemorrhagic shock was induced by blood withdrawing and the mean blood pressure was maintained at 40-45mmHg for 120min. Resuscitation was then performed by infusion of shed blood/saline mixtures. After monitoring for another 8h, rats were sacrificed.


RESULTS
Histology findings and lung injury score analysis revealed moderate lung injury in rats of the HS, HS-D, and HS-K groups, whereas those of the HS-D+K group revealed mild lung injury. The effects of haemorrhagic shock on increasing cell number and protein concentration in bronchoalveolar lavage fluid as well as water content, leukocyte infiltration, and myeloperoxidase activity of lung tissues were significantly attenuated by dexmedetomidine-ketamine combination but not by dexmedetomidine or ketamine alone. Dexmedetomidine-ketamine combination, but not dexmedetomidine or ketamine alone, also significantly inhibited haemorrhagic shock-induced upregulation of pulmonary inflammatory molecules, including nitric oxide, prostaglandin E(2), chemokine (e.g., macrophage inflammatory protein-2), and cytokines [e.g., interleukin (IL)-1beta, and IL-6].


CONCLUSIONS
Dexmedetomidine-ketamine combination mitigates acute lung injury in haemorrhagic shock rats.
Yang
Chen-Hsien
CH
Department of Anaesthesiology, Mackay Memorial Hospital, Taipei, Taiwan.
Tsai
Pei-Shan
PS
Wang
Tao-Yeuan
TY
Huang
Chun-Jen
CJ
D055371:Acute Lung Injury / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D020927:Dexmedetomidine / Q000008:administration & dosage*; D004338:Drug Combinations; D018836:Inflammation Mediators / Q000378:metabolism; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage*; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000473:pathology; D008297:Male; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D018836:Inflammation Mediators; D020927:Dexmedetomidine; D007649:Ketamine; D009195:Peroxidase