The effects of ketamine, midazolam and ketamine/xylazine on acute lung injury induced by α-naphthylthiourea in rats.

Objectives: Ketamine is a drug used in human and veterinary medicine, primarily for the induction and maintenance of general anesthesia, analgesia (particularly in emergency medicine), and treatment of bronchospasm. Midazolam is the preferred drug in intensive care units for sedation and anesthesia. Ketamine/xylazine combination is used as an anesthetic agent in veterinary medicine and experimental animals. Aside from anaesthetic properties, these agents can cause physiologic and metabolic alterations and modulate and improve the inflammatory responses. The objective of the present study was to investigate the effects of ketamine, midazolam, and veterinary and experimentally used ketamine/xylazine combination in acute lung injury induced by α-naphthylthiourea (ANTU).

Material And Methods: ANTU was injected intraperitoneally (i.p.) in rats at the dose of 10 mg/kg. Ketamine (15, and 50 mg/kg, i.p.), midazolam (2 and 4 mg/kg, i.p.), and ketamine/xylazine (50/10 mg/kg, i.p.) administered to rats 30 min prior to ANTU. Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. Histopathological changes were documented in each lung tissue, including intra-alveolar hemorrhage, alveolar edema and inflammation. The severity of the lung injury was scored (0-3).

Results: Ketamine, midazolam and ketamine/xylazine had a significant prophylactic effect on pleural effusion formation at all doses and significantly reduced pleural effusion. Ketamine caused a significant reduction of inflammation, hemorrhage and edema scoring and midazolam (2 mg/kg) and ketamine/xylazine caused a significant reduction of inflammation and edema scoring.

Conclusions: It can be concluded that ketamine and midazolam may attenuate lung injuries induced by ANTU. In addition to their anesthetic or sedative properties, the prophylactic effects of these agents on lung tissue damage will contribute to the treatment of intensive care unit diseases including acute lung injury. Similarly, the effects of these agents on lung pathophysiology should be considered in experimental applications.