SUMMARY1. The ventilatory response to square-wave challenges in end-tidal partial pressure of CO2 (Pc02) was investigated at three levels of arterial Po0 (Pa°2) in nineteen anaesthetized 2-to 11-day-old piglets.2. The ventilatory responses, measured on a breath-to-breath basis, were separated into a peripheral and a central component using a two-compartment model. Both components were described by a CO2 sensitivity, a time constant, a time delay and a single offset.3. Fifty-six responses were analysed against a background ofnormoxaemia (Pa°2 = 12 70 +0O72 kPa, mean + S.D.), fifty-three against a background of moderate hypoxaemia (Pao = 8-63 +034 kPa) and fifty-one against a background of severe hypoxaemia (Pa,02 = 4-98 +030 kPa).4. The sensitivity of the peripheral chemoreceptors in mediating the response to C02 increased from 38-3 + 17-0 ml min-kPa-1 kg-1 during normoxaemia to 48-8 + 15-3 ml min-kPa-1 kg-' during moderate hypoxaemia and to 72-9 + 24-0 ml min-1 kPa-1 kg-1 at severe hypoxaemia.5. As compared with the central CO2 sensitivity during moderate hypoxaemia and normoxaemia (1040± 39-0 and 1008 + 41 6 ml min' kPa-1 kg-', respectively) it decreased to 85 9 + 54-1 ml min-' kPa-1 kg-1 at severe hypoxaemia. 6. We conclude that in newborn piglets there is a positive interaction between hypoxia and hypercapnia at the level of the peripheral chemoreceptors while severe hypoxaemia reduced the C02 sensitivity centrally.

ABSTRACT. In 20 piglets aged 2-12 d (mean 6.8 d) and control the ventilation. Studies from Belenky et a!. (6) and anesthetized with a-chloralose-urethane, we investigated Bureau and Begin (7) suggest that in the lamb the peripheral the contribution of the peripheral and central chemorecep-chemoreceptors continue to maturate after the resetting in the tors to the ventilatory response to inhalation of CO2 in air. first 2 d after birth. The ventilatory response to hypoxia and For this purpose we used the dynamic end-tidal forcing hyperoxia as well as the response to potassium cyanide showed technique, applying square-wave changes in end-tidal C 0 2 an increase until about 10 d of life. In this paper, animals in tension of 1.5-2.0 kPa at a constant end-tidal O2 tension which a major part of the peripheral chemoreceptor resetting has of 15 kPa. Each response, measured on a breath-to-breath occurred (age at least 2 d) will be called young animals to basis, was separated into a fast peripheral and a slow distinguish them from newborns. central component by fitting the sum of two exponentiafsIn contrast to the amount of information about the hypoxic to the measured ventilation. Each component was charac-and hyperoxic ventilatory response, studies of the ventilatory terized by a C 0 2 sensitivity, a time constant, a time delay, response to C 0 2 in young animals are sparse. The question of and an apneic threshold. The results showed that in 2-to whether the carotid chemoreceptors in young animals contribute 12-d-old piglets the peripheral chemoreceptors are respon-to the ventilatory response to C 0 2 inhalation during air breathing sive to CO2 during air breathing. The contribution of the has not been answered. There is some indirect information from peripheral chemoreceptors in mediating the response to steady state techniques in which the COz-slope is compared C02 averaged 30 f 10%. Within this age range we could before and after denervation of the peripheral chemoreceptors.not demonstrate a significant correlation of the parameters In lambs 1 to 10 d old (8), denervation of the carotid bodies led characterizing the dynamic ventilatory response to C 0 2 to a slight decrease in C02-slope, an increased latency time, and with postnatal age. (Pediatr Res 30: [491][492][493][494][495] 1991) a slower rate of rise of ventilation in response to inhaled C02, suggesting that at least a part of the COz response was dependent Abbreviations on the fast-responding peripheral chemoreceptors. Furthermore, an age-related change in C02-slope could not be detected. In DEF, dynamic end-tidal forcing monkeys the COz-slope increased between 2 and 2 1 d (9). Human PETco2, end-tidal partial COz pressure infants showed an increase in COz-slope of 62% from 2 to 27 d PETo2, end-tidal partial 0 2 pressure of postnatal life (10). However, to the best of our knowledge S, COz-slo~e, the slope of the ventilatory response to C02 there are no studies about to what extent the peripheral and S,, peripheral ventilatory C 0 2 sensitivity central chemorec...

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1. Indomethacin, a cyclo-oxygenase inhibitor, decreases baseline values of cerebral blood flow, attenuates the cerebrovascular sensitivity to C02 and stimulates ventilation in newborn piglets. 2. In twelve newborn anaesthetized piglets we investigated the influence of indomethacin on the ventilatory response to C02 using the dynamic end-tidal forcing technique by applying square-wave changes in end-tidal C02 tension of 1P5-2-0 kPa at constant endtidal PO 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 C02 sensitivity, a time constant, a time delay and an apnoeic threshold. 4. The results showed that indomethacin increases the central C02 sensitivity from 232 + 38 to 292 + 43 ml min1 kPa' (mean + S.E.M.). Neither the peripheral C02 sensitivity nor the apnoeic threshold changed. 5. The central on-transient and off-transient time constants increased from 500 + 7-4 and 81'0 + 9'6 s, respectively, to 6941 + 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.Indomethacin, a cyclo-oxygenase inhibitor, is commonly used in the treatment of patent ductus arteriosus in newborns. Furthermore, intravenous and intraventricular administration of indomethacin has been found to stimulate ventilation in newborn piglets. The mechanism by which indomethacin stimulates breathing has not been elucidated, although reductions in stable brain prostaglandins are likely to play a role (Long, 1988). Recent studies have shown that indomethacin decreases baseline values of cerebral blood flow (CBF) and attenuates the cerebrovascular sensitivity to both increases and decreases in

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