Ventilatory response to keto-doxapram in intact and carotid body denervated lambs

We aimed to investigate the role of the carotid bodies in the ventilatory response to keto-doxapram, and whether this response was dose-dependent; we studied two group (n = 5 per group) of awake, intact and carotid-body denervated (CBD) lambs, aged 10-15 days. At 20 min intervals, they received 0.5, 1.0, 2.5 and 5.0 m g/kg mg/kg of keto-doxapram as an intravenous bolus infusion. Plasma keto-doxapram was measured (HPLC). Ventilation was recorded via a face mask and a pneumotachograph. In intact lambs, an immediate dose-dependent increase in minute ventilation (V1) was observed. At 2 min, VI increased from baseline by 125 +/- 28, 212 +/- 49, 378 +/- 41 and 637 +/- 92 mol.kg 1.min 1 (mean +/- SE, P less than 0.01) corresponding to the foregoing incremental doses. A significant correlation was observed between the peak VI and the corresponding plasma keto-doxapram concentrations (r = 0.73, P less than 0.0003). In CBD lambs, VI increased significantly less than in intact animals. In conclusion, early ventilatory response to keto-doxapram depends mainly on intact carotid bodies, and the effect is dose-dependent.