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Central Modulation of Arterial Chemoreceptor Control by Midazolam during Severe Arterial Hypoxia in the Rabbit

The ventilatory response to arterial hypoxia and carotid body chemoreceptor activity are depressed by midazolam but the effects on the integrated chemoreflex arc are unknown. This study tested the postulate that midazolam selectively modifies components of intense autonomic activity evoked by the arterial chemoreflex during severe arterial hypoxia (PaO2 < 35 mm Hg). Female NZ White rabbits (n=10) were cannulated via an ear artery and vein (lidocaine 1%). Minute ventilation (VE), tidal volume (VT), respiratory frequency (f), heart rate (HR), mean arterial pressure (MAP) and SpO2 were measured breathing room air, followed by 5 minutes of hypoxia (FiO2 7‐8%). After recovery, rabbits breathed room air during i.v. midazolam, followed by matched hypoxia. Two doses of midazolam (0.78 mg/kg bolus + 0.66 mg/kg/h or 1.56 mg/kg bolus + 1.32 mg/kg/h) were studied, each on separate days. Arterial blood samples were taken for blood gas analysis and drug assay. Data were analysed using repeated measures ANOVA. Midazolam caused a fall in f, VE and MAP while VT and HR increased (P<0.01). During midazolam infusion the hypoxia induced reflex bradycardia observed in conscious rabbits was reversed (P<0.001), whereas MAP, VE and VT responses were maintained. Midazolam produced sedation but rabbits remained responsive. Midazolam is therefore selectively inhibitory on vagal control of heart rate during the response to severe hypoxia, while other reflex components appear functionally intact. We have shown previously the central vagus is sensitive to some anesthetics, suggesting midazolam action is also central, rather than at the carotid body. Funding: ANZCA and HMRI