The influence of indomethacin on the ventilatory response to CO2 in newborn anaesthetized piglets

1. Indomethacin, a cyclo-oxygenase inhibitor, decreases baseline values of cerebral blood flow, attenuates the cerebrovascular sensitivity to CO2 and stimulates ventilation in newborn piglets. 2. In twelve newborn anaesthetized piglets we investigated the influence of indomethacin on the ventilatory response to CO2 using the dynamic end-tidal forcing technique by applying square-wave changes in end-tidal CO2 tension of 1.5-2.0 kPa at constant end-tidal PO2 of 15 kPa. 3. Each response, measured on a breath-to-breath basis, is separated into a fast peripheral and a slow central component with each component characterized by a CO2 sensitivity, a time constant, a time delay and an apnoeic threshold. 4. The results showed that indomethacin increases the central CO2 sensitivity from 232 +/- 38 to 292 +/- 43 ml min-1 kPa-1 (mean +/- S.E.M.). Neither the peripheral CO2 sensitivity nor the apnoeic threshold changed. 5. The central on-transient and off-transient time constants increased from 50.0 +/- 7.4 and 81.0 +/- 9.6 s, respectively, to 69.1 +/- 9.8 and 139.9 +/- 13.4 s after indomethacin. 6. Using a physiological model we argue that the respiratory effects of indomethacin are due to effects on cerebral blood flow.