Dexmedetomidine–ketamine combination mitigates acute lung injury in haemorrhagic shock rats

Abstract

Aim of the study 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 40–45 mmHg for 120 min. Resuscitation was then performed by infusion of shed blood/saline mixtures. After monitoring for another 8 h, 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)-1β, and IL-6]. Conclusions Dexmedetomidine–ketamine combination mitigates acute lung injury in haemorrhagic shock rats.