Dexmedetomidine Modification of the Chemoreflex Response to Severe Arterial Hypoxia in the Rabbit

Abstract

The carotid body contains alpha‐2 adrenoceptors but selective agonists given during hypoxia have shown inhibition or enhancement of carotid sinus nerve activity in vivo (1), and in vitro (2). Dexmedetomidine (DM) is a highly‐selective alpha‐2 adrenergic agonist currently used for clinical sedation and analgesia (3,4) but its effects on integrated chemoreflex control during hypoxia are unknown. We examined the hypothesis that DM would selectively alter components of the cardiorespiratory responses to severe arterial hypoxia (PaO2 <35 mm Hg). An ear artery and vein of 6 New Zealand White female rabbits were cannulated (lidocaine 2%). Mean arterial pressure (AP), arterial blood gases, heart rate (HR), minute ventilation (VE), tidal volume (VT), respiratory frequency (f) and oxygen saturation (ear SpO2) were measured breathing room air, followed by 5 minutes of hypoxia (FiO2 7–8%). After a one‐hour recovery period, the measurements were repeated during intravenous DM infusions (4 or 40 mcg/kg/hr), breathing room air followed by exposure to a matched hypoxic stimulus. One dose of DM was studied on each of two experimental days, one week apart. Behavioural responses were recorded before and during DM infusions. Data were analysed using two‐way repeated measures ANOVA. Significant differences were accepted at the p<0.05 level. In the absence of DM, hypoxia alone evoked a reflex fall in HR and f, with increases in VT, VE and AP. In rabbits breathing room air, DM alone caused dose‐dependent falls in f, VE, HR and AP, while VT was unchanged. With DM plus hypoxia, the reflex bradycardia was absent at the higher dose. The increase in VT remained intact during both doses, while the rise in VE was attenuated due to an unchanged f. The AP increased from a lowered baseline. DM produced dose‐dependent sedation. We conclude reflex vagal control of heart rate during severe hypoxia is modified by DM. There are dose‐dependent effects on AP and components of ventilation. The increase in VT in response to hypoxia during DM infusion indicates that chemotransduction at the carotid body is intact. The data suggest the main sites of action of dexmedetomidine on cardiorespiratory control during hypoxia are within the CNS and not at the carotid body.Support or Funding InformationJohn Hunter Hospital Charitable Trust and Hunter Medical Research InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.