Imidazoline 1 receptor activation preserves respiratory drive in spontaneously breathing newborn rats during dexmedetomidine administration.
BACKGROUND
Dexmedetomidine is an alpha-2 (α2) adrenoceptor and imidazoline 1 (I1) receptor agonist that provides sedation without loss of respiratory drive.


OBJECTIVE
The aim of this study was to elucidate the involvement of α2-adrenoceptor and I1receptor 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-1atipamezole (selective α2-adrenoceptor antagonist) or efaroxan (α2-adrenoceptor/I1receptor 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-1atipamezole or 1 mg·kg-1efaroxan completely ameliorated the dexmedetomidine-associated reduction in heart rate (HR). The addition of 1 mg·kg-1atipamezole or 1 or 5 mg·kg-1efaroxan completely ameliorated the dexmedetomidine-associated reduction in respiratory frequency. Mean inspiratory flow (VT/TI; VTis tidal volume and TIis 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-1atipamezole, 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-1efaroxan, respectively).


CONCLUSIONS
Our results suggest that in newborn rats undergoing dexmedetomidine sedation, the α2-adrenoceptor, but not I1receptor, is involved in the regulation of HR and respiratory frequency, and that activation of the I1receptor plays a major role in the maintenance of respiratory drive.
Department of Dental Anesthesiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Nana
N
Sato
Department of Physiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Chikako
http://orcid.org/0000-0002-4291-7912
C
Saiki
Department of Physiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Junko
J
Tamiya
Department of Physiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Toshio
T
Imai
Department of Dental Anesthesiology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Katsuhisa
K
Sunada
D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature; D020927:Dexmedetomidine / Q000494:pharmacology*; D004328:Drive; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D054755:Imidazoline Receptors / Q000819:agonists*; D010991:Plethysmography; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D006993:Hypnotics and Sedatives; D054755:Imidazoline Receptors; C410887:imidazoline I1 receptors; D020927:Dexmedetomidine
atipamezole; breathing pattern; dexmedetomidine anesthesia; efaroxan; heart rate; neonates