Abolition of ventilatory response to caffeine in chemodenervated lambs

In this study we have evaluated the role of the peripheral chemoreceptors in the ventilatory response to caffeine at a dose currently used in human infants for treatment of central apneas (10 mg/kg). Twelve lambs were studied; six had carotid body denervation (CBD) and six had a sham denervation (intact). The denervation was done the 2nd wk of life, and the study of the response to caffeine infusion was carried out at a mean age of 82 days. The awake and nonsedated animals received 10 mg/kg of caffeine, and caffeine blood levels were, respectively, 8.8 and 9.0 mg/l in the intact and in the CBD lambs. The intact lambs responded to caffeine by a significant immediate increase in minute ventilation (V̇E) of 46% from 274 to 400 ml·min^-1·Kg^-1 (P < 0.001), 1 min after caffeine infusion. This response rapidly faded, but V̇E was still increased at 2 h, 314 ml·min^-1·kg^-1. The increase in ventilation was brought about by a change in mean inspiratory flow (VT/TI), which increased from 9.9 to 14.0 ml·s^-1·kg^-1 within 1 min (P < 0.01); VT/TI was still increased at 11.2 ml·s^-1·kg^-1 2 h later. In contrast, for the CBD lambs there was no response to caffeine infusion as measured by V̇E or VT/TI. We conclude that 1) bolus caffeine infusion produces a rapid response in V̇E followed by a fall in V̇E that remained above base line until at least 2 h postinfusion, and 2) the intact chemoreceptor function appears as an essential mediator for these increases in ventilation, since the peripheral chemodenervation has completely abolished the V̇E response to this particular dose of caffeine.