Dexmedetomidine-induced pulmonary alterations in sheep.
Alpha(2) agonist-induced pulmonary oedema in sheep might be related to alterations in pulmonary haemodynamics and/or activation of inflammatory processes. In seven sevoflurane-anaesthetized sheep pulmonary haemodynamics, arterial oxygen tensions, nitric oxide and prostaglandin E(2) concentrations were determined before and after intravenous dexmedetomidine (2microg kg(-1)). In a second trial, lung tissue was sampled for histopathology and quantitative real-time PCR for IL-1beta and iNOS mRNA in a control sheep and 2, 10 and 30min after dexmedetomidine. Computer tomography of the lung under sevoflurane anaesthesia before and after dexmedetomidine was performed. Two minutes after dexmedetomidine mean pulmonary artery pressure, pulmonary arterial occlusion pressure and estimated capillary pressurewere significantly increased to 34.5mmHg, 22.2mmHg and 27.1mmHg, respectively. On computer tomography, lung density increased immediately after dexmedetomidine, with maximal density occurring between 9 and 12min. Histopathology was consistent with vascular congestion followed by protein and erythrocyte extravasation into alveoli. Increased iNOS mRNA levels were detected in sevoflurane anaesthetized animals only. An IL-1beta signal occurred after morphological changes had occurred in lung tissue. These findings support hydrostatic stress as the underlying cause of alpha(2) agonist-induced pulmonary oedema in sheep.