THE INFLUENCE OF INDOMETHACIN ON THE VENTILATORY RESPONSE TO CO2 IN NEWBORN ANESTHETIZED PIGLETS

1. Indomethacin, a cyclo-oxygenase inhibitor, decreases baseline value s of cerebral blood flow, attenuates the cerebrovascular sensitivity t o CO2 and stimulates ventilation in newborn piglets. 2. In twelve newb orn anaesthetized piglets we investigated the influence of indomethaci n on the ventilatory response to CO2 using the dynamic end-tidal forci ng technique by applying square-wave changes in end-tidal CO2 tension of 1.5-2.0 kPa at constant end-tidal P-O2 of 15 kPa. 3. Each response, measured on a breath-to-breath basis, is separated into a fast periph eral and a slow central component with each component characterized by a CO2 sensitivity, a time constant, a time delay and an apnoeic thres hold. 4. The results showed that indomethacin increases the central CO 2 sensitivity from 232 +/- 38 to 292 +/- 43 ml min(-1) kPa(-1) (mean /- S.E.M.). Neither the peripheral CO2 sensitivity nor the apnoeic thr eshold changed. 5. The central on-transient and off-transient time con stants increased from 50.0 +/- 7.4 and 81.0 +/- 9.6 s, respectively, t o 69.1 +/- 9.8 and 139.9 +/- 13.4 s after indomethacin. 6. Using a phy siological model we argue that the respiratory effects of indomethacin are due to effects on cerebral blood flow.