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The effect of ambient temperature on oxygen consumption and triiodothyronine in the developing lamb
292 2--6 weeks of age hut uncommon in younger animals where BF is higher [1]. Ambient temperature (T) has an age-dependent effection on BF suggesting that metabolic rate is also important in controlling breathing [2]. The role of laryngeal constriction and the effect of upper airway by-pass on breathing in relation to ambient temperature during SWS in developing lambs was therefore studied. Ten newborn lambs with a reversible tracheostomy and thyroarytenoid (TA) EMG electrodes implanted under fluothane anaesthesia when 2 days old, were then studied between 5 and 30 ° T and 4 and 55 days of age. BF, tidal volume, and thoraco-abdominal movements (by inductance plethysmography), rectal temperature ( T ) , oxygen consumption (VO2), were measured at each T, alternately with an intact upper airway and with a tracheal window open during SWS. Laryngeal braking was judged from the T EMG and from the presence or absence of a shoulder on the inductance sum signal which indicated air retention in the lung. Laryngeal constriction was more common in older lambs which had lower BF and lower basal VO2 than when 4 days old. A marked increase in the use of this mechanism was seen with increasing T after 14 days of age except when panting occurred (upper critical limit) as VO2 and minute ventilation fell. In these older lambs a warm T and a low VO 2resulted in irregular, often periodic, breathing when the upper airway was bypassed. These results indicate that there is an increasing importance of vagal airway mechanisms for respiratory rhymogenesis during development. Consequently we speculate that in early postnatal life the high metabolic rate (thermogenic and nonthermogenic), acts as a major stimulus to breathing and expiratory time is short. As thermal efficiency increases, metabolic rate and BF fall and expiratory time lengthens. Then a loss of expiratory pressure, sensed by vagal~airway stretch receptors [1], results in loss of rhythm. This demonstrates the changing importance of thermometabolism in the 'tonic' drive to breathing in perinatal life. 1 Johnson, P. (1979): In: Central nervous control mechanisms in breathing, pp. 337--351. Editors: C. von Euler and H. Lagercrantz. 2 Andrews, D.C., Fedorko, L., Johnson, P. and Wollner, J.C. (1985): In: The Physiological Development of the Fetus and Newborn, pp. 821--825. Editors: C.T. Jones and P.W. Nathanielsz. The effect of ambient temperature on oxygen consumption and triiodothyronine in the developing lamb. M. Symonds, D.C. Andrews, K. Magee and P. Johnson, Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford, U.K.
In the lamb basal metabolic rates rises rapidly following birth and then falls over the first 8 weeks of life. It has also been shown that the lower and upper critical temperatures decrease within 36 h postpartum, indicating that thermoregulatory adaptation to the extrauterine environment commences from birth [1]. This process may be related to changes in thyroid function which has been shown to play an important role in the metabolic response to cold exposure in neonatal lambs [2]. We have investigated adjustments in metabolic rate in response to altering ambient temperature (T) close to operant conditions (not summit challenge) and its relationship to triiodothyronine (T3) during neonatal development. Eight newborn lambs were housed in T between 14 and 21 °C and fed an ad lib formula milk diet. Following implantation of femoral arterial catheters under fluothane anaesthetic on day 2. Lambs aged 4, 14, 30 and 45 days were sequentially studied after being maintained at 5, 10, 15, 20, 25 and 30°C for at least 1 h. Oxygen consumption (VO 2) was measured at each T during slow wave sleep and a plasma sample taken for T3 measurement. Rectal temperature (To) was monitored. Within the thermoneutrai range significant falls in VO2 occurred between day 4 and subsequent ages. In 4-day-old lambs VO 2 increased at T below 25°C, whilst in 14-day lambs VO2 only rose below 10°C. Older lambs did not show significant changes in VO 2 with T. Plasma T3 concentrations closely followed both the decline in metabolic rate with age and changes in VO 2 with T. Shivering was not observed in lambs aged 4 days but was in lambs aged 14 days at 5 and 10°C (and some 30 day lambs at 5°C). This suggests that non-shivering thermogenesis is responsible for increased VO2 in cold T in the early neonatal period ( T 5°C + ). Furthermore panting resulted in young lambs at 30°C, whilst older lambs usually panted at 25°C. Basal Tr e rose by day 14 and remained above fetal and adult values. Small increases in T occurred with thermogenesis and -lysis (panting).
293 On the basis of significant changes in VO 2 and the occurrence of shivering and panting at different T it is concluded that thermal efficiency of the lamb increases with age. This response appears to be closely related to plasma T3 concentrations, indicating that thyroid hormones exerts a major influence on temperature regulation in the growing lamb. l 2
Mercer et al. (1979): J. Therm. Biol., 4, 239--245. Cabello (1983): Biol. Neonate, 44, 224--233.
Anomalies in the Cushing response. A.M. Kaiser and A.G.L. Whitelaw, Hammersmith Hospital, London, U.K. Maintenance of cerebral perfusion pressure (CPP) is crucial to the adequate perfusion of the brain. CPP is reduced by an increase in intracranial pressure (ICP), but this is offset by the responsive rise in mean arterial pressure (MAP). The existence of this "Cushing response" in human neonates has not been systematically studied, although it has been described in one asphyxiated baby [1]. We have measured MAP and ICP simultaneously in 20 babies likely to have intracranial hypertension. MAP was measured invasively or by oscillometry. ICP was measured at CSF cannulation, mostly through subarachnoid catheter. Six hundred and four values of CPP, calculated as the difference between MAP and ICP, were obtained. In the five subjects where ICP rose by > 20 mmHg, there was a linear relationship of MAP to ICP in three and CPP to ICP in four. With increasing ICP, MAP was static in one and rose in two of these and two others, at a mean rate of rise of 0.71 mmHg/mmHg. CPP fell with increasing ICP in all four of these and two others, at a mean rate of 1.13 mmHg/mmHg. Significant relationships tended to occur in older babies, with a wider range of ICPs. Even so, CPP always fell progressively with rising ICP. To preserve adequate cerebral perfusion in the neonate with intracranial hypertension, raised ICP must be managed aggressively as MAP may not rise sufficiently to compensate. 1 Raju, T.N.K., Vidyasagar, D. and Papazafiratou, C. (1981): Crit. Care Med., 9, 449--453.
Response to dopamine and dobutamine in the preterm infant < 30 weeks gestation. V.M. Miall-Allen and A.G.L. Whitelaw, Department of Paediatrics and Neonatal Medicine, Hammersmith Hospital, London, U.K. Dopamine, _ dobutamine, is used to treat shock in infants but the responses have not been investigated in infants < 30 weeks' gestation. We used continuous computer-acquired data for heart rate (HR) and mean arterial pressure (MAP) from 60 min before to 90 min after the start of/or change in, each inotrope infusion. The study population consisted of 12 infants (mean gestational age 27 weeks, mean weight 899 g) and each received initially 5/ag/kg per min of dopamine which was increased after > 90 min to 10/ag/kg per min. In those failing to produce a sustained response to the latter, dobutamine was added at 10 gg/kg per min. The infants were retrospectively grouped into those surviving > 28 days, "survivors", and those dying < 28 days, "non-survivors". Neither group demonstrated a sustained increase in MAP with 5/ag/kg per min of dopamine, but with 10/ag/kg per min a rise of 8.1 __ 2.7 mmHg was seen in the "survivors" and 6.0 - 1.6 mmHg in the "non-survivors" (P < 0.001). This response was not sustained in the "non-survivors" beyond 90 min and dobutamine was added (10 #g/kg per min) but failed to produce any further elevation of MAP. There was a small but statistically insignificant rise in HR at the start of each infusion.
In the lamb basal metabolic rates rises rapidly following birth and then falls over the first 8 weeks of life. It has also been shown that the lower and upper critical temperatures decrease within 36 h postpartum, indicating that thermoregulatory adaptation to the extrauterine environment commences from birth [1]. This process may be related to changes in thyroid function which has been shown to play an important role in the metabolic response to cold exposure in neonatal lambs [2]. We have investigated adjustments in metabolic rate in response to altering ambient temperature (T) close to operant conditions (not summit challenge) and its relationship to triiodothyronine (T3) during neonatal development. Eight newborn lambs were housed in T between 14 and 21 °C and fed an ad lib formula milk diet. Following implantation of femoral arterial catheters under fluothane anaesthetic on day 2. Lambs aged 4, 14, 30 and 45 days were sequentially studied after being maintained at 5, 10, 15, 20, 25 and 30°C for at least 1 h. Oxygen consumption (VO 2) was measured at each T during slow wave sleep and a plasma sample taken for T3 measurement. Rectal temperature (To) was monitored. Within the thermoneutrai range significant falls in VO2 occurred between day 4 and subsequent ages. In 4-day-old lambs VO 2 increased at T below 25°C, whilst in 14-day lambs VO2 only rose below 10°C. Older lambs did not show significant changes in VO 2 with T. Plasma T3 concentrations closely followed both the decline in metabolic rate with age and changes in VO 2 with T. Shivering was not observed in lambs aged 4 days but was in lambs aged 14 days at 5 and 10°C (and some 30 day lambs at 5°C). This suggests that non-shivering thermogenesis is responsible for increased VO2 in cold T in the early neonatal period ( T 5°C + ). Furthermore panting resulted in young lambs at 30°C, whilst older lambs usually panted at 25°C. Basal Tr e rose by day 14 and remained above fetal and adult values. Small increases in T occurred with thermogenesis and -lysis (panting).
293 On the basis of significant changes in VO 2 and the occurrence of shivering and panting at different T it is concluded that thermal efficiency of the lamb increases with age. This response appears to be closely related to plasma T3 concentrations, indicating that thyroid hormones exerts a major influence on temperature regulation in the growing lamb. l 2
Mercer et al. (1979): J. Therm. Biol., 4, 239--245. Cabello (1983): Biol. Neonate, 44, 224--233.
Anomalies in the Cushing response. A.M. Kaiser and A.G.L. Whitelaw, Hammersmith Hospital, London, U.K. Maintenance of cerebral perfusion pressure (CPP) is crucial to the adequate perfusion of the brain. CPP is reduced by an increase in intracranial pressure (ICP), but this is offset by the responsive rise in mean arterial pressure (MAP). The existence of this "Cushing response" in human neonates has not been systematically studied, although it has been described in one asphyxiated baby [1]. We have measured MAP and ICP simultaneously in 20 babies likely to have intracranial hypertension. MAP was measured invasively or by oscillometry. ICP was measured at CSF cannulation, mostly through subarachnoid catheter. Six hundred and four values of CPP, calculated as the difference between MAP and ICP, were obtained. In the five subjects where ICP rose by > 20 mmHg, there was a linear relationship of MAP to ICP in three and CPP to ICP in four. With increasing ICP, MAP was static in one and rose in two of these and two others, at a mean rate of rise of 0.71 mmHg/mmHg. CPP fell with increasing ICP in all four of these and two others, at a mean rate of 1.13 mmHg/mmHg. Significant relationships tended to occur in older babies, with a wider range of ICPs. Even so, CPP always fell progressively with rising ICP. To preserve adequate cerebral perfusion in the neonate with intracranial hypertension, raised ICP must be managed aggressively as MAP may not rise sufficiently to compensate. 1 Raju, T.N.K., Vidyasagar, D. and Papazafiratou, C. (1981): Crit. Care Med., 9, 449--453.
Response to dopamine and dobutamine in the preterm infant < 30 weeks gestation. V.M. Miall-Allen and A.G.L. Whitelaw, Department of Paediatrics and Neonatal Medicine, Hammersmith Hospital, London, U.K. Dopamine, _ dobutamine, is used to treat shock in infants but the responses have not been investigated in infants < 30 weeks' gestation. We used continuous computer-acquired data for heart rate (HR) and mean arterial pressure (MAP) from 60 min before to 90 min after the start of/or change in, each inotrope infusion. The study population consisted of 12 infants (mean gestational age 27 weeks, mean weight 899 g) and each received initially 5/ag/kg per min of dopamine which was increased after > 90 min to 10/ag/kg per min. In those failing to produce a sustained response to the latter, dobutamine was added at 10 gg/kg per min. The infants were retrospectively grouped into those surviving > 28 days, "survivors", and those dying < 28 days, "non-survivors". Neither group demonstrated a sustained increase in MAP with 5/ag/kg per min of dopamine, but with 10/ag/kg per min a rise of 8.1 __ 2.7 mmHg was seen in the "survivors" and 6.0 - 1.6 mmHg in the "non-survivors" (P < 0.001). This response was not sustained in the "non-survivors" beyond 90 min and dobutamine was added (10 #g/kg per min) but failed to produce any further elevation of MAP. There was a small but statistically insignificant rise in HR at the start of each infusion.