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

• Published in: Pediatric anesthesia Vol. 27; no. 5; pp. 506 - 515
• Main Authors: Sato, Nana, Saiki, Chikako, Tamiya, Junko, Imai, Toshio, Sunada, Katsuhisa, Vutskits, Laszlo
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.05.2017
• Subjects: Adrenergic alpha-2 Receptor Agonists - pharmacology; Adrenergic alpha-2 Receptor Antagonists - pharmacology; Anesthesia; Animals; Animals, Newborn; atipamezole; Body Temperature; breathing pattern; Dexmedetomidine - pharmacology; dexmedetomidine anesthesia; Drive; efaroxan; Electrocardiography - drug effects; Female; heart rate; Heart Rate - drug effects; Hypnotics and Sedatives - pharmacology; Imidazoline Receptors - agonists; neonates; Plethysmography; Pregnancy; Rats; Rats, Wistar; Respiration - drug effects; Rodents; breathing pattern; heart rate; efaroxan; neonates; atipamezole; dexmedetomidine anesthesia
• ISSN: 1155-5645; 1460-9592
• DOI: 10.1111/pan.13107

Summary 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 (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). 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.