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 (VE) of 46% from 274 to 400 ml X min-1 X kg-1 (P less than 0.001), 1 min after
caffeine infusion. This response rapidly faded, but VE was still increased at 2 h, 314 ml X min-1 X 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 X s-1 X kg-1 within 1 min (P less than 0.01); VT/TI was still increased at 11.2 ml X s-1 X kg-1 2 h later. In contrast, for the CBD lambs there was no response to
caffeine infusion as measured by VE or VT/TI. We conclude that bolus
caffeine infusion produces a rapid response in VE followed by a fall in VE that remained above base line until at least 2 h postinfusion, and the intact chemoreceptor function appears as an essential mediator for these increases in ventilation, since the peripheral
chemodenervation has completely abolished the VE response to this particular dose of
caffeine.