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Study Objective: To investigate the efficacy of warmed, humidified inspired oxygen (O(2)) for the treatment of mildly hypothermic postoperative patients., Design: Prospective, randomized, unblinded clinical trial., Setting: Postanesthesia care unit in a tertiary care hospital., Patients and Interventions: 30 ASA physical status I, II, and III patients following intraabdominal surgical procedures were randomly assigned to receive either routine O(2) therapy (control group, n = 15), or warmed (42 degrees C) humidified O(2) (treatment group, n = 15) for the initial 90 postoperative minutes., Measurements: Core (tympanic) temperature, dry mouth score and shivering score., Main Results: Tympanic temperature was similar in both groups on admission ( approximately 35.8 degrees C). Rewarming rate in the first postoperative hour was greater in the treatment group (0.7 +/- 0.1 degrees C. hr(-1)) compared to the control group (0.4 +/- 0.1 degrees C. hr(-1)) (p = 0.03). Patients receiving the warmed, humidified O(2) had a lower incidence of dry mouth compared to the control group (p = 0.03). The incidence of shivering was low and similar in both groups., Conclusions: Warming and humidifying inspired O(2) hastens recovery from hypothermia in postoperative patients.

The O2 sensitivity of carotid chemoreceptor type I cells is low just after birth and increases with postnatal age. Chronic hypoxia during postnatal maturation blunts ventilatory and carotid chemoreceptor neural responses to hypoxia, but the mechanism remains unknown. We tested the hypothesis that chronic hypoxia from birth impairs the postnatal increase in type I cell O2 sensitivity by comparing intracellular Ca2+ concentration ([Ca2+]i) responses to graded hypoxia in type I cell clusters from rats born and reared in room air or 12% O2. [Ca2+]i levels at 0, 1, 5, and 21% O2, as well as with 40 mM K+, were measured at 3, 11, and 18 days of age with use of fura 2 in freshly isolated cells. The [Ca2+]i response to elevated CO2/low pH was measured at 11 days. Chronic hypoxia from birth abolished the normal developmental increase in the type I cell [Ca2+]i response to hypoxia. Effects of chronic hypoxia on development of [Ca2)]i responses to elevated K+ were small, and [Ca2+]i responses to CO2 remained unaffected. Impairment of type I cell maturation was partially reversible on return to normoxic conditions. These results indicate that chronic hypoxia severely impairs the postnatal development of carotid chemoreceptor O2 sensitivity at the cellular level and leaves responses to other stimuli largely intact.

Infants of smoking mothers are at increased risk of SIDS, one cause of which is thought to be due to impaired ventilatory responses. We tested the hypotheses that prenatal nicotine exposure impairs the development of dynamic carotid chemoreceptor-driven ventilatory responses, and reduces the ability to lower metabolic rate in hypoxia. Osmotic minipumps were implanted into 20 pregnant rats at day 3 of gestation to deliver nicotine (6 mg/kg per day free base) or saline for 4 weeks. Minute ventilation was recorded breath by breath in rat pups at 3, 8 and 18 days (n = 6, 8 and 6) postnatal in response to 5-sec challenges of 100% O2 (Dejours test) and 5% O2 + 5% CO2. Carotid sinus nerve (CSN) responses to hypoxia and CO2 were recorded from 22 control and 17 nicotine-exposed preparations at ages between 3-20 days. Oxygen consumption (V(O)2) was measured in groups of pups at 3 days (n = 7 each for nicotine and control) and 8 days (n = 5 each for nicotine and control) in room air and 10% O2. There was no detectable effect of nicotine exposure on the development of CSN responses. Ventilatory responses to 5% O2-5% CO2 increased with age but did not differ between nicotine and control groups. Ventilatory responses to 100% O2 were unaffected by nicotine exposure at 8 and 18 days. However, the 3-day nicotine group showed no significant response to 100% O2 whereas V(E) was significantly reduced in the control group by 100% O2. There was no significant effect of nicotine exposure on the ability to reduce oxygen consumption in hypoxia at 3 or 8 days, but at 3 days, baseline (room air) variability in oxygen consumption was greater in the nicotine group. We conclude that nicotine exposure appears to result in abnormal ventilatory responses to withdrawal of baseline peripheral chemoreceptor drive during a period of early postnatal life. We speculate that a transient abnormality could contribute to a period of instability and increased vulnerability to challenges.

The site of postnatal maturation of carotid body chemoreception is unclear. To test the hypothesis that maturation occurs synchronously in type I cells and the whole carotid body, the development of changes in the intracellular Ca2+ concentration responses to hypoxia, CO2, and combined challenges was studied with fluorescence microscopy in type I cells and compared with the development of carotid sinus nerve (CSN) responses recorded in vitro from term fetal to 3-wk animals. Type I cell responses to all challenges increased between 1 and 8 days and then remained constant, with no multiplicative O2-CO2 interaction at any age. The CSN response to hypoxia also matured by 8 days, but CSN responses to CO2 did not change significantly with age. Multiplicative O2-CO2 interaction occurred in the CSN response at 2-3 wk but not in younger groups. We conclude that type I cell maturation underlies maturation of the CSN response to hypoxia. However, because development of responses to CO2 and combined hypoxia-CO2 challenges differed between type I cells and the CSN, responses to these stimuli must mature at other, unidentified sites within the developing carotid body.

1. Carotid chemoreceptor sensitivity is minimal immediately after birth and increases with postnatal age. In the present study we have investigated the peri- and postnatal developmental time course of [Ca2+]i responses to hypoxia in clusters of type I cells isolated from near-term fetal rats and rats that were 1, 3, 7, 11, 14 and 21 days old, using the Ca2+-sensitive fluoroprobe fura-2. 2. In type I cells from all age groups a graded increase in [Ca2+]i occurred in response to lowering the PO2 from 150 mmHg to 70, 35, 14, 7, 2 and 0 mmHg. The graded [Ca2+]i response to hypoxia was hyperbolic at all ages. 3. Type I cells from rats near-term fetal to 1 day old exhibited small [Ca2+]i responses, mainly to the most severe levels of hypoxia. After day 1, an increase in the [Ca2+]i responses to submaximal hypoxia stimulation resulted in a rightward shift in the O2 response curve. Using the Delta[Ca2+]i between 35 and 2 mmHg PO2 as an index of O2 sensitivity, type I cell O2 sensitivity increased approximately 4- to 5-fold between near-term fetal to 1 day old and 11 to 14 days of age. 4. Exposure to elevated extracellular potassium (10, 20 and 40 mM K+) caused a dose-dependent [Ca2+]i rise in type I cells from all age groups. There were no age-related changes in [Ca2+]i responses to any level of K+ between near-term fetal and 21 days. 5. We conclude that the maximal type I cell [Ca2+]i response to anoxia, as well as the sensitivity to submaximal hypoxic stimulation, of rats aged from near-term fetal to 21 days depends on the level of postnatal maturity. The lack of an age-related increase in the [Ca2+]i response to elevated K+ during the timeframe of maximal development of O2 sensitivity suggests that resetting involves maturation of O2 sensing, rather than non-specific developmental changes in the [Ca2+]i rise resulting from depolarization.

Peripheral chemoreceptors are commonly thought to respond to hypoxia by releasing neurotransmitters from the type 1 cells of the carotid body; these molecules then bind to post-synaptic receptors on the carotid sinus nerve. The tachykinin substance P (SP) may act as an important neurotransmitter/neuromodulator in hypoxic chemotransmission in peripheral arterial chemoreceptors. In order to elucidate the role of SP in modulating hypoxic chemotransmission, we have used quantitative in situ hybridization histochemistry, to determine the effect of hypoxia on SP gene induction, and the localization of neurokinin 1 (NK-1) receptor mRNA in the carotid body and petrosal ganglia complex in rats at 21 days post-natal age. For comparison, we also determined: (1) the effect of hypoxia on tyrosine hydroxylase (TH) gene induction and (2) the localization of the mRNA encoding the D2-dopamine receptor. SP mRNA was not detected in the rat carotid body during normoxia and its expression was not induced after a 1 h of exposure to hypoxia (10% O2/90% N2), a stimulus that was sufficient to cause a significant increase (P < 0.01) in TH mRNA levels in the carotid body. Both SP and TH mRNAs were abundantly expressed in multiple cells in the petrosal and the jugular ganglia. However, these mRNAs were not co-localized and SP and TH mRNA levels were not affected by hypoxia in these ganglia. Although D2-dopamine receptor mRNA was abundantly expressed in the rat carotid body, we found no evidence of NK-1 receptor mRNA in the carotid body. In contrast, both NK-1 receptor mRNA and D2-dopamine receptor mRNA were present in petrosal ganglion cells. In the rat, SP does not appear to modulate hypoxic chemotransmission by being made in and released from type 1 cells in the carotid body, and neither does SP modulate the activity of type 1 cells by binding to NK-1 receptors on these cells.

Maternal smoking increases the risk of the sudden infant death syndrome (SIDS) 2-4-fold. The mechanism is unknown but may be related to hypoxia responses. Recovery from hypoxic apnea by young mammals depends on gasping and bradycardia. We asked whether prenatal nicotine exposure, reported to reduce hypoxic survival in 2 day old rat pups, acted by impairing gasping or bradycardia. Pregnant rats were infused throughout gestation and 1 week postnatally with nicotine tartrate (NIC) 12 mg/kg per day or saline (CON). Maternal plasma nicotine was 134.4 +/- 42 ng/ml, significantly reducing pup body weight. Pups at 3-28 days were exposed to anoxia (97% N2/3% CO2) until gasping ceased, while breathing and heart rate were recorded. NIC and CON groups were not significantly different at any age, in baseline heart rate, respiratory rate, the time course for bradycardia, time to gasp onset, duration of gasping, or number of gasps, although most of these variables declined significantly with age. We conclude that responses to anoxia are not affected by prenatal high-dose nicotine.

The risk of SIDS is increased up to fourfold by maternal smoking, by an unknown mechanism. We tested the hypothesis that prenatal nicotine exposure can cause abnormal postnatal development of breathing control. Osmotic minipumps were implanted into pregnant rats to deliver either nicotine bitartrate (6 mg kg-1 day-1) (NIC) or saline (CON) throughout gestation and for 1 week postnatal. NIC and CON rat pups from 4 age groups (means 3, 8, 18 and 34 days) were studied. Ventilation was recorded at 30 degrees C in air and after 10 min at FIO2 = 0.1 and 0.15, and at FICO2 = 0.05. Ventilatory responses to FIO2 = 0.1 and FICO2 = 0.05 showed significant changes with age but were unaffected by NIC at all ages. The weak respiratory responses to FIO2 = 0.15 were unaffected by NIC or age. Oxygen consumption in normoxia and hypoxia, and hypoxic depression of oxygen consumption, declined with age but were not affected by NIC. We conclude that NIC exposure alone has no detectable effect on the postnatal development of respiratory responses to moderate levels of hypoxia or hypercapnia for short periods. However, effects of NIC on the responses to more severe or prolonged stimuli cannot be ruled out.

The results of these studies are consistent with the hypothesis that carotid chemoreceptor type-I cell resetting occurs, at least in part, at the level of the type-I cell. Furthermore, we have developed an in vitro model of newborn type-I cell resetting, in which freshly isolated glomus cells from newborns exhibit small, immature [Ca2+]i response to anoxia, but-after 72 hours in culture-[Ca2+]i responses convert to adult magnitude and profile. Finally, work so far suggests that glomus cell resetting in this model is modulated by oxygen tension. The mechanisms of glomus cell resetting remain unknown. Resetting of O2 sensitivity could result from withdrawal of tonic inhibitory influences present in vivo, changes in the oxygen sensor itself, changes in ion channel expression, modulation, and function, or other mechanisms occurring around the time of birth. Additional work is needed to determine the mechanisms of glomus cell resetting at the cellular level, and the role of O2 tension and other potential modulators of resetting.

The carotid chemoreceptor response to hypoxia is weak just after birth and increases during postnatal development. The mechanisms underlying chemoreceptor maturation are unknown. We tested the hypothesis that carotid chemoreceptor maturation occurs at the glomus cell level by measuring intracellular calcium ([Ca2+]i) mobilization in response to hypoxia, anoxia, and NaCN in freshly dissociated cells from newborn vs. adult rabbit carotid bodies. Cells were loaded with fura 2 and superfused at 37 degrees C with balanced salt solution equilibrated with 5% CO2. [Ca2+]i mobilization in response to 3-min challenges of hypoxia (PO2 approximately 15 mmHg), anoxia (PO2 approximately 0 mmHg), and NaCN (1 mM) was measured using a digital imaging microscope. The fluorescence intensity ratio was used to calculate [Ca2+]i. Peak [Ca2+]i responses to all three challenges were three- to fivefold greater in glomus cells from adult compared with newborn carotid chemoreceptors. In addition, the average normoxic [Ca2+]i baseline was approximately threefold higher in the adult glomus cells. These results suggest that carotid chemoreceptor glomus cell sensitivity to natural stimuli, as reflected by the [Ca2+]i response, depends on the level of postnatal maturity.

It has been postulated that the weak carotid chemoreceptor responses of neonatal mammals may be due to inhibition produced by high levels of endogenous dopamine release or exaggerated sensitivity to dopaminergic inhibition. This was studied by measuring the effect of domperidone, a selective dopamine D2-receptor antagonist, on the carotid chemoreceptor response to O2 and CO2 in anesthetized neonatal and adult cats. The animals were exposed to four levels of isocapnic O2 (arterial PO2 of approximately 35-45, 55-65, 80-90, > 300 Torr) and four levels of isoxic CO2 (end-tidal PCO2 of approximately 21, 40, 58, and 78 Torr) before and after D2-receptor blockade. Whole nerve activity was recorded from the carotid sinus nerve (CSN). Both neonatal and adult cats increase CSN activity during hypoxia and hypercapnia (P < 0.001). Domperidone caused an increase in CSN activity at all O2 levels in adults (P < 0.01) but only during hypoxia in neonates (P < 0.001). Domperidone caused an increase in CSN activity during normo- and hypercapnia in adults but only during hypercapnia in neonates (P < 0.001). Domperidone approximately doubled an index of hypoxic sensitivity in the normoxia-hypoxia range (100 to 40 Torr) in the neonatal group but had little effect on sensitivity to hypoxia in adults. We conclude that the inhibitory role of endogenous dopamine in the carotid chemoreceptors changes with postnatal development.

This study aimed to characterize neural responses of the carotid chemoreceptors of the maturing cat to natural stimuli and to determine the time course of carotid chemoreceptor development from the neonatal period to adulthood. Carotid sinus nerve (CNS) responses to O2 and CO2 were studied in cats at 1, 4, and 8 wk of age and in adult cats (n = 6 at each age). Pentobarbital sodium-anesthetized cats were exposed to three levels of O2 (arterial PO2 = 40-45, 80-90, and > 300 Torr) at five levels of arterial PCO2 (22, 35, 48, 63, and 75 Torr) while the moving average of whole nerve output from the CSN was recorded. Ganglioglomerular nerves were sectioned. All cats at every age increased CSN activity during hypoxia. However, the CSN response to hypoxia was not sustained in some immature cats. Of the cats that sustained CSN activity during hypoxia, four of the six 1-wk-old cats showed a biphasic pattern of response, with an initial overshoot followed by a steady level of discharge. Older cats did not exhibit this pattern. CNS sensitivity to hypoxia was weakest in 1-wk-old kittens but increased to nearly adult levels by 4 wk of age. Carotid chemoreceptor responses to CO2 were also smallest in 1-wk-old kittens and increased with maturation. However, unlike hypoxia responses, CO2 sensitivity during hypoxia continued to develop between 8 wk and adulthood. O2-CO2 interaction did not become significant until after 4 wk of age. Thus, carotid chemoreceptor responses to both O2 and CO2 are weak in newborn cats and increase during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Interference with fetal breathing movements is known to retard morphologic development of the lung and to reduce compliance. We hypothesized that the lower compliance might be in part due to effects on lung structural proteins. We studied the effects of phrenic nerve section in utero on lung compliance and on the lung contents of collagen, elastin, and DNA. At 110 to 112 days of gestation, one fetal lamb in each of 12 twin pregnancies had either both phrenic nerves cut (PX) or a sham operation (S). The other twin was left unoperated (Upx, Us) as a control. They were killed 14 to 22 days later, and the concentrations in lung parenchyma of collagen (as hydroxyproline HPro), elastin, and DNA were measured, together with lung compliance and dry and wet weight. Paired comparisons were made (PX versus Upx and S versus Us). Both operated groups (PX, S) had smaller lungs with lower water content than did their unoperated twins. Absolute static compliance in PX was reduced, but compliance relative to lung weight was unchanged, and there was no significant difference between S and Us. There were no significant effects of PX on the concentrations of HPro, elastin, and DNA, or on the elastin/collagen ratio. Compliance was not correlated with either HPro or elastin content. HPro content increased significantly with gestational age in all groups. It is concluded that phrenic nerve section retards the increase of lung compliance and possibly air space, but it does not affect the overall rate of lung cell proliferation or of deposition of elastin or collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxia inhibits fetal breathing movements but after birth it stimulates breathing. These differences have long been thought to involve central nervous inhibitory mechanisms. Such mechanisms might exert a tonic inhibition of fetal breathing movements at normal fetal PaO2 and the rise in PaO2 at birth might lift this inhibitory effect. To test this hypothesis 7 fetal sheep were chronically instrumented at 125-130 days for recording electrocortical activity (ECoG), and the electromyograph (EMG) activity of the diaphragm and neck muscles. Catheters were placed in a fetal carotid and a brachial artery and in the fetal trachea. For an extracorporeal membrane oxygenation system a 12 F gauge silastic catheter was placed in the right atrium for draining fetal blood and a 9.6 F gauge catheter was placed in a carotid artery to return oxygenated blood. Three days after operation the fetuses were connected to the extracorporeal membrane oxygenation system and fetal PaO2 was raised to 65.2 +/- 4.4 mmHg (SEM) for 6 to 19 h without changing pH or PaCO2. Neither the incidence of high voltage ECoG (48.5 +/- SEM 2.0% vs 52.8 +/- 3.3%) nor of fetal breathing movements (37.3 +/- 2.6% vs 23.8 +/- 5.9%) changed during the periods of hyperoxia. Since fetal breathing movements did not become continuous, we conclude that the lower PaO2 in the fetus compared to the neonate does not exert a tonic inhibitory influence on fetal breathing movements.

Clonidine is a recommended antihypertensive for use during pregnancy, although little is known of its fetal effects. This study examines the effects of clonidine on breathing and sleep-state cycling in fetal lambs. Clonidine was infused into a fetal lateral ventricle for up to 24 hours at 128 to 135 days' gestation. Control infusions of artificial cerebrospinal fluid had no effect. Clonidine infusion significantly reduced the incidence and episode duration of fetal breathing for the duration of the infusion period. Cycling of electrocortical activity became irregular and rapid, and the incidence of high-voltage electrocortical activity (equivalent to quiet sleep) was reduced. Fetal heart rate decreased but arterial pressure was unaffected. After infusion the breathing incidence and episode duration both increased significantly compared with control, with continuous high-amplitude breathing for several hours, whereas the incidence of high-voltage electrocortical activity remained low. Because lung development is promoted by fetal breathing, long-term use of clonidine during pregnancy could slow lung development by reducing fetal breathing activity.

In order to investigate possible mechanisms for the effect of hypoxia on fetal electrocortical (ECoG) activity, the effects of 30 min of isocapnic hypoxia on ECoG were studied in three groups of unanaesthetized late-gestation fetal lambs in utero. One group was intact, in the second the brainstem was transected between the colliculi, and in the third the carotid sinus nerves and cervical vagosympathetic trunks were cut bilaterally to denervate the systemic arterial chemoreceptors. The incidence of high voltage (HV) ECoG activity was lower in brainstem-transected fetuses than in the other groups. All three groups showed an increased number of changes from low to high voltage and an increase in the incidence of HV activity at the onset of hypoxia, but the increases reached statistical significance only in the brainstem-transected group. It is concluded that the onset of hypoxia is often associated with an increase in HV ECoG activity, with the most consistent changes occurring after brainstem transection and similar but smaller increases in intact and denervated fetuses. Thus the response of fetal electrocortical activity to the onset of hypoxia does not depend on intact connections with the lower brainstem. However, the effect of hypoxia on fetal ECoG is minor and inconsistent and may be physiologically unimportant.

In the unanesthetized fetal sheep the administration of morphine causes initial apnoea followed by hyperpnoea. We thought that a section of the brain at midcollicular level might separate these two effects. Therefore we sectioned the brain stem of five fetuses at 132 +/- 1 (SEM) days of gestation and compared their responses to morphine (17 experiments) with that observed in seven intact fetuses at similar gestational ages (15 experiments). Brain stem sections were confirmed morphologically and histologically. Morphine, 1 mg/kg was injected in the fetal jugular vein during low-voltage electrocortical activity (ECoG). We measured ECoG, eye movements, diaphragmatic activity, blood pressure and amniotic pressure. Sectioned fetuses before the administration of morphine had a complete dissociation between ECoG and breathing activity. With the administration of morphine we found: (i) the length of the apnoea was 139.8 +/- 15.5 min in sectioned fetuses and 17.0 +/- 5.8 min in intact fetuses (P less than 0.01); and (ii) there was no hyperpneic response in the sectioned fetus whereas the length of hyperpnoea in the intact group was 99.1 +/- 11.8 min (P less than 0.001). The results support the idea of two central distinct areas of action of morphine in the fetal brain. The absence of hyperpnoea in the sectioned fetuses suggests that neurons inhibiting the 'respiratory neurons' are located rostrally to the mid-collicular line.

Recordings were made of nervous activity from duck arterial chemoreceptors, arterial baroreceptors and pulmonary receptors during steady-state conditions (normoxic normocapnia, hypoxia, and hypercapnia) and apnoeic asphyxia. Arterial chemoreceptors were stimulated by hypoxia and intra-arterial KCN injection and showed an increasing discharge throughout asphyxia. During the first 2 min of asphyxia the time course of the development of asphyxic bradycardia paralleled that of the increase in arterial chemoreceptor discharge. Arterial baroreceptors discharged at a constant latency from the heart beat when mean arterial pressure was constant, while a drug-induced increase in mean arterial pressure was associated with a reduced latency and increased baroreceptor activity per heart-beat. During asphyxia mean arterial pressure often rose so that, despite the effect of bradycardia, baroreceptor activity per heart-beat and activity per unit time increased. Pulmonary receptors showed a linear relationship (negative slope) between discharge rate and % CO2 in inspired air and usually stopped firing in apnoeic asphyxia. The initiation and maintenance of diving bradycardia are discussed in terms of these results.

The role of nasal heat exchange in the control of brain temperature has been studied in cats, pigs, ducks and rabbits during acute experiments under general anaesthesia. Nasal air flow at physiological rates caused hypothalamic temperature to fall at between 0.2 and 0.5 degrees C/min in cats, pigs and ducks, which all have arterial rete systems that can cool blood flowing to the brain, but not in rabbits, which lack an arterial rete. Bilateral stimulation of cervical sympathetic trunks reduced or abolished the brain cooling effect of nasal air flow in cats, pigs and ducks. After a period of airflow during which brain cooling was reduced by sympathetic stimulation, the end of stimulation was sometimes followed by marked and rapid brain cooling, indicating re-perfusion through ischaemic cooled tissues. Cervical sympathetic stimulation caused a reduction in resistance to nasal airflow in all species studied, by inducing vasoconstriction and shrinkage of the nasal mucosa. In species with well-developed arterial retia, the effect of cervical sympathetic stimulation in regulating nasal cooling of the brain is probably mediated by controlling blood flow through the nasal mucosa. Although this vascular control also occurs in rabbits, they cannot selectively cool the brain and sympathetic stimulation has no effect on rabbit brain temperature.

1. Nasal vasomotor oscillations were studied in 23 anaesthetised cats. The oscillations occurred in all cats and showed both respiratory (vasoconstriction in inspiration) and non-respiratory rhythms. In all cases the oscillations were asymmetrical between the two sides of the nose, and the side with greater oscillations also had a higher level of nasal vasoconstriction. 2. Oscillations shifted from one side to the other, both spontaneously and in response to stimulation of the brain-stem reticular formation. Induced shifts were nearly always to the stimulated side, and preceded by ipsilateral vasoconstriction and contralateral vasodilation. This reciprocal pattern was shown in 19 out of 89 responsive sites, and is similar to changes shown spontaneously in the nasal cycle. 3. Non-respiratory oscillations were seen at some time in most preparations and varied from frequency doubling to complete independence from respiration. 4. The evidence presented indicated that nasal vasomotor oscillations are driven from sympathetic oscillators which may be independent of, or can be entrained by, central respiratory activity. The oscillators show reciprocal inhibition, and electrical stimulation over a poorly-defined area of the brainstem reticular formation can shift the balance of activity between them, though responses from any one site depend on the existing state of the oscillating system.

Five adult male dik-dik (Madoqua kirkii) were exposed in a climatic chamber to an air temperature of 45 degrees C. Measurements were made of rectal temperature (Tre) and respiratory frequency (f) and arterial blood samples taken before and during heat exposure were analyzed for pH, PCO2 and PO2. During exposure, Tre and f increased in all animals. In the first 80 min dik-dik displayed thermal tachypnea and minor changes in blood gases. Continued exposure lead to hyperpnea accompanied by a fall in PaCO2 and a rise in pH. PaCO2 at first fell and then increased toward or above control levels. The dik-dik did not display second phase breathing. This observation confirms that second phase breathing is not essential to the development of respiratory alkalosis. The main conclusion of the study is that the dik-dik, unlike another heat-adapted antelope, the wildebeest (Taylor, Robertshaw, and Hoffmann. Am. J. Physiol. 217:907-910, 1969), is unable to resist alkalosis during heat stress.

Measurements have been made on respiration of three resting unstressed adult giraffe under normal conditions. Tracheal dimensions and body dimensions have also been measured in a large number of giraffe and other mammals. The results indicate that contrary to statements in the literature the giraffe does not have an abnormally large dead space, though the trachea is abnormally long and narrow. The respiratory measurements indicate that the giraffe breathes as predicted by published scaling equations, and at rest shows no abnormalities of rate or depth. The respiratory evaporative water loss is very small. Body temperature is labile with a range of at least 3.3 degrees C, and oxygen consumption, respiratory frequency, minute volume and respiratory evaporative water loss are all strongly correlated with body temperature.

1. The microvasculature of the lung of the duck and pigeon was studied by scanning electron microscopy of vascular casts and critical point dried preparations of the gas exchange tissue. 2. The gas-exchange cappilaries are discrete tubular vessels intimately associated with air capillaries in a three dimensional network. 3. The capillaries originate from arteries at the periphery of the parabronchus, and are collected by veins which run close to its luminal surface. 4. The capillary bed of 3-5 atria is drained by a single vein. It is suggested that the vein and its associated capillaries may form a controllable subunit of pulmonary perfusion.

In experiments to assess its value in the study of fetal arterial chemoreceptor reflexes, doxapram (0.5 - 2 mg i.a.) given to unanaesthetized fetal lambs in utero in low voltage electrocortical activity stimulated fetal breathing in 73% of trials. The response began within a few seconds and lasted up to 5 min. This response to doxapram was present in intact or mid-collicular brainstem transected fetuses and after bilateral section of the carotid sinus nerves and cervical vagosympathetic trunks (denervation). In intact and brainstem transected fetuses, doxapram injections were followed by a modest rise in arterial pressure and a small fall in heart rate. After denervation the rise in arterial pressure was fourfold and the heart rate increased. Electrocortical activity and limb movements were not affected in any group of lambs, and fetal breathing was not induced during isocapnic hypoxia. It is concluded that doxapram stimulates fetal breathing by a central action below the pons, and that it can therefore not be used to study peripheral arterial chemoreceptor function in utero.

The contribution of systemic arterial baroreceptors to the cardiovascular adjustments to diving has been investigated in unanesthetized ducks after acute baroreceptor denervation. Both intact and denervated ducks exhibited bradycardia on diving, although denervated ducks showed a lesser and more variable fall in heart rate. Hindlimb vascular resistance rose significantly in both intact and denervated ducks. Continuous stimulation of one depressor nerve, through miniature electrodes implanted on the cut central end, resulted in a diving bradycardia intermediate between that recorded in intact and denervated animals. Intermittent stimulation of the depressor nerve, for 20-s periods, at intensities high enough to cause a large fall in mean arterial pressure (MAP) predive caused a smaller reduction in MAP as a dive was prolonged, due to a large decline in the ability of the baroreceptor reflex to affect peripheral resistance. There was no change in the effect of stimulation on cardiac control before or during diving. The present experiments indicate that a barostatic reflex, which exerts its effects primarily through cardiac control and not control of total peripheral resistance, is active through the dive but that the majority of the diving response in ducks is independent of baroreceptor integrity.

1. The alpha 2-adrenergic agonist clonidine was given by aortic injection to three groups of unanaesthetized fetal lambs in utero near term. One group was intact, the second had the brain stem transected just above the pons, and the third had bilateral section of the carotid sinus nerves and cervical vagi. 2. Clonidine had similar effects in all three groups. Electrocortical activity entered a high-voltage, low-frequency episode: breathing, neck and limb movements ceased; arterial pressure remained unchanged or increased; heart rate fell or remained unchanged, and the variation in both heart rate and blood pressure was much reduced. This state lasted 10-20 min, and was followed by a period of up to 4 h during which the cycling of electrocortical activity was rapid and irregular. 3. The alpha 2-adrenergic antagonist idazoxan (0.5-2.0 mg I.A.) blocked all the actions of clonidine. When given alone it usually induced a short period of low-voltage electrocortical activity and stimulated breathing movements. These effects were present in both the intact and brain-stem-transected groups, though the stimulation of breathing was significantly reduced by brain-stem transection. There were no consistent effects on heart rate or blood pressure. 4. The effects of clonidine on fetal heart rate and electrocortical activity were similar to those described in adults, but it also had inhibitory effects, not present in adults, on fetal breathing and somatic movements.

In intact fetal lambs near term there was a statistically significant relation between regular small uterine contractions and a change to high-voltage fetal electrocortical activity (excess above chance 15%) or arrest of breathing (excess 12%). Isocapnic hypoxia also arrested fetal breathing. After brain stem transection there was no relation between uterine contractions and the fetal electrocortical activity, but isocapnic hypoxia increased the rate and depth of fetal breathing. Similarly uterine contractions were to a small extent associated with the initiation of fetal breathing movements which continued for about as long as the contraction. We conclude that the occasional effects of uterine contractions are consistent with diminished fetal cranial oxygen supply.

The effect of spontaneous changes in high or low voltage electrocortical activity, in the absence of uterine contractions, on the regional distribution of blood flow was studied in normoxic unanaesthetized fetal sheep at 124-134 days gestation in utero, using the isotope-labelled microsphere method. On transition from high to low voltage there was a significant fall in arterial pressure (7%) and an increase in flow (19-38%) to areas of the brain corresponding to the arborization of the reticular formation, i.e. excluding the cerebrum and cerebellum. Blood flow to the gastro-intestinal tract, pancreas and liver (portal vein) also increased.

Injections of 100 micrograms apomorphine (I.A.) in intact unanaesthetized fetal lambs resulted in the onset of low-voltage electrocortical activity if not already present, onset or an increase in amplitude of fetal breathing movements, and in about 50% of experiments, onset or an increase in skeletal muscle activity. These responses also occurred during isocapnic hypoxia, though the stimulation of breathing was less than in normoxic lambs. Apomorphine had no consistent effects on the blood gases, pH, heart rate or blood pressure. In fetal lambs with the carotid nerves and vago-sympathetic trunks sectioned, apomorphine had the same effects as in intact lambs, except that there was a small fall in arterial O2 pressure (Pa,O2). Haloperidol (0.5-1 mg I.V.) had no effect on spontaneous breathing movements or electrocortical activity, but blocked all responses to apomorphine for several hours. Dopamine (up to 4 mg I.V.) caused an increase in arterial pressure accompanied by bradycardia, but had no effect on breathing movements or electrocortical activity. After suprapontine brain-stem transection, the electrocortical response to apomorphine was reduced. The respiratory response was lost or reversed, with apomorphine causing a reduction in amplitude of breathing. Haloperidol reduced the incidence of breathing movements for several hours in brain-stem-transected fetuses. We conclude that there is a central pathway, including at least one dopaminergic synapse and with components above the pons, which can stimulate fetal motor activity and breathing. It does not appear to be tonically active and its normal function is unknown.

Oxygen consumption (VO2), heart rate, body temperature, and stride frequency were measured in Marabou storks walking on a treadmill at a range of speeds and gradients. VO2 was linearly related to speed at gradients up to 11 degrees and speeds up to 1.4 m . s-1, and the slope of the VO2/speed regression increased with the treadmill angle up to 9 degrees. At 11 degrees there was a fall in the slope. Analysis indicates the cost of horizontal movement of about 1.1 ml O2 . m-1 (mean wt 4.5 kg). The cost of vertical movement is 7.13 ml O2 . m-1 and the efficiency about 30%. Maximum recorded VO2 was about five times resting, and there was no indication of an oxygen debt at any value for VO2. Heart rate was directly proportional to vO2 over the range studied, and at high heart rates successive cardiac cycles overlapped. Body temperature did not change significantly during exercise. Stride frequency was linearly related to walking speed but with a nonzero intercept so that stride length changed with speed, but there was no observed change in gait with speed. These data are discussed in comparison with published scaling equations and with data from mammals.

Lung denervation in ducks, by sectioning all vagal branches to one lung following mid-cervical vagotomy on the other side, resulted in immediate bradycardia and fall in breathing frequency. Some 3-5 weeks after lung denervation breathing frequency was within the normal range but the lung inflation reflex, present in unilaterally vagotomized sham-operated ducks, was abolished. During 2 min dives there were no significant differences between sham-operated and denervated ducks in heart rate, arterial blood pressure, blood gas tensions and pH(a). However, during recovery from diving heart rate increased more slowly in denervates and breathing rate was significantly below that attained by shams, although tidal volume rose to a maximum increase of 139% to a maximum of 225% of the pre-dive value in denervates in contrast to a maximum increase of 139% of pre-dive in sham-operated ducks. Both sham-operated and denervated ducks exhibited a significant fall in diastolic blood pressure 60 sec after emergence...