Effects of dexmedetomidine on respiratory mechanics and control of breathing in normal rats

Dexmedetomidine is a highly selective and specific alpha(2)-adrenergic agorist, with sedative, analgesic, and sympatholytic activities. The aim of the present study was to define the effects of DMED in respiratory mechanics in normal rats. In addition, lung morphometry was studied to determine whether the physiological changes reflected underlying morphological changes defining the sites of action of dexmedetomidine. Arterial blood gases were also determined. Twelve adult Wistar rats were randomly assigned to two groups of six animals each: PENTO and DMED. In PENTO group animals were sedated (diazepam, 5 mg, i.p.) and anaesthetised with pentobarbital sodium (20 mg kg(-1) i.p.). The rats of the DMED group received dexmedetomidine (250 mu g kg(-1) i.p. followed by intravenous infusion of 0.5 mu g kg(-1) h(-1)). In spontaneously breathing rats, minute ventilation, respiratory frequency, and neuromuscular inspiratory drive were lower in dexmedetomidine group, which also presented hypercapnia, whereas tidal volume, inspiratory, expiratory, and total respiratory cycle times were higher in dexmedetomidine group compared to the PENTO group. During mechanical ventilation, respiratory mechanical parameters were similar in both groups. These findings were supported by the absence of histological changes. In conclusion, under the conditions studied, dexmedetomidine did not change respiratory mechanical parameters and lung histology, but induced ventilatory depression. (c) 2006 Elsevier B.V. All rights reserved.