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

Abstract

Background: Dexmedetomidine is an alpha-2 (α₂ ) adrenoceptor and imidazoline 1 (I₁ ) receptor agonist that provides sedation without loss of respiratory drive.

Aims: The 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.

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^-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.

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^-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 (V_T /T_I ; V_T is tidal volume and T_I 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).

Conclusions: Our 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.

Keywords: atipamezole; breathing pattern; dexmedetomidine anesthesia; efaroxan; heart rate; neonates.