Effects of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing newborn rats.

Summary Background Dexmedetomidine, a selective α2-adrenoceptor agonist, is a new sedative agent. Objective To examine the dexmedetomidine-associated changes in cardiorespiratory indices in spontaneously breathing newborn rats. Methods An abdominal catheter to administer drugs and subcutaneous electrodes to record electrocardiographic data were inserted into 2- to 4-day-old rats under isoflurane anesthesia; the rats were then placed in individual chambers. After recovery from the anesthesia, the rats received intraperi-toneal administrations of normal saline (NS, vehicle), dexmedetomidine (50 μg·kg−1), or dexmedetomidine (50 μg·kg−1) followed 5 min later with NS or the selective α2-adrenoceptor antagonist atipamezole (1 mg·kg−1) (n = 10 in each group). Cardiorespiratory indices were recorded for each animal throughout the experiment. Results Dexmedetomidine administration significantly decreased heart rate (HR) and minute ventilation (V′E) (P < 0.05) compared with control, whereas NS administration did not. The decrease in HR and V′E after dexmedetomidine administration was significantly less in rats that received atipamezole (P < 0.05) than in those that received NS after dexmedetomidine administration. The dexmedetomidine-associated V′E depression was attributed to a significant decrease in respiratory frequency (fR) but not tidal volume (VT). The change in fR was reversed by atipamezole administration, which itself induced no significant changes in HR and fR. Conclusion In spontaneously breathing immature rats, dexmedetomidine administration significantly reduced HR and V′E. Because atipamezole fully reversed decreases in fR and therefore V′E, dexmedetomidine-related respiratory suppression occurs predominantly through α2-adrenoceptor-related suppression of fR.