Dexmedetomidine-induced pulmonary alterations in sheep

Alpha2 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 E2 concentrations were determined before and after intravenous dexmedetomidine (2 μg kg−1). In a second trial, lung tissue was sampled for histopathology and quantitative real-time PCR for IL-1β and iNOS mRNA in a control sheep and 2, 10 and 30 min 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 34.5 mmHg, 22.2 mmHg and 27.1 mmHg, respectively. On computer tomography, lung density increased immediately after dexmedetomidine, with maximal density occurring between 9 and 12 min. 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-1β signal occurred after morphological changes had occurred in lung tissue.These findings support hydrostatic stress as the underlying cause of alpha2 agonist-induced pulmonary oedema in sheep.