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Paediatric anaesthesia · May 2017
Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration.
- Nana Sato, Chikako Saiki, Junko Tamiya, Toshio Imai, and Katsuhisa Sunada.
- Department of Dental Anesthesiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
- Paediatr Anaesth. 2017 May 1; 27 (5): 506-515.
BackgroundDexmedetomidine is an alpha-2 (α2 ) adrenoceptor and imidazoline 1 (I1 ) receptor agonist that provides sedation without loss of respiratory drive.AimsThe aim of this study was to elucidate the involvement of α2 -adrenoceptor and I1 receptor in the cardiorespiratory changes induced by dexmedetomidine in spontaneously breathing newborn rats.MethodsAn abdominal catheter to administer drugs and three subcutaneous electrodes to record electrocardiographic data were inserted into 2- to 5-day-old Wistar rats under isoflurane anesthesia. In individual chambers, each rat was intraperitoneally administered dexmedetomidine (50 μg·kg(-1) ) followed 5 min later by normal saline or 1, 5, or 10 mg·kg(-1) atipamezole (selective α2 -adrenoceptor antagonist) or efaroxan (α2 -adrenoceptor/I1 receptor antagonist). Cardiorespiratory indices were recorded before and after drug administration.ResultsThe administration of dexmedetomidine alone resulted in significant changes to most of the cardiorespiratory indices examined. The addition of 5 or 10 mg·kg(-1) atipamezole or 1 mg·kg(-1) efaroxan completely ameliorated the dexmedetomidine-associated reduction in heart rate (HR). The addition of 1 mg·kg(-1) atipamezole or 1 or 5 mg·kg(-1) efaroxan completely ameliorated the dexmedetomidine-associated reduction in respiratory frequency. Mean inspiratory flow (VT /TI ; VT is tidal volume and TI is inspiratory time), which is an index of respiratory drive, was not significantly affected by the administration of dexmedetomidine alone (P = 0.273) or dexmedetomidine + atipamezole (P = 0.605, 0.153, 0.138 for 1, 5, 10 mg·kg(-1) atipamezole, respectively); however, it was significantly decreased after the administration of dexmedetomidine + efaroxan (P = 0.029, <0.001, <0.001 for 1, 5, 10 mg·kg(-1) efaroxan, respectively).ConclusionsOur results suggest that in newborn rats undergoing dexmedetomidine sedation, the α2 -adrenoceptor, but not I1 receptor, is involved in the regulation of HR and respiratory frequency, and that activation of the I1 receptor plays a major role in the maintenance of respiratory drive.© 2017 John Wiley & Sons Ltd.
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