Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration.

BACKGROUND

Dexmedetomidine is an alpha-2 (α ) adrenoceptor and imidazoline 1 (I ) receptor agonist that provides sedation without loss of respiratory drive.

AIMS

The aim of this study was to elucidate the involvement of α -adrenoceptor and I receptor in the cardiorespiratory changes induced by dexmedetomidine in spontaneously breathing newborn rats.

METHODS

An 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 ) followed 5 min later by normal saline or 1, 5, or 10 mg·kg atipamezole (selective α -adrenoceptor antagonist) or efaroxan (α -adrenoceptor/I receptor antagonist). Cardiorespiratory indices were recorded before and after drug administration.

RESULTS

The administration of dexmedetomidine alone resulted in significant changes to most of the cardiorespiratory indices examined. The addition of 5 or 10 mg·kg atipamezole or 1 mg·kg efaroxan completely ameliorated the dexmedetomidine-associated reduction in heart rate (HR). The addition of 1 mg·kg atipamezole or 1 or 5 mg·kg efaroxan completely ameliorated the dexmedetomidine-associated reduction in respiratory frequency. Mean inspiratory flow (V /T ; V is tidal volume and T 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 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 efaroxan, respectively).

CONCLUSIONS

Our results suggest that in newborn rats undergoing dexmedetomidine sedation, the α -adrenoceptor, but not I receptor, is involved in the regulation of HR and respiratory frequency, and that activation of the I receptor plays a major role in the maintenance of respiratory drive.