Dynamic ventilatory responses to CO2 in the awake lamb: role of the carotid chemoreceptors.

In awake lambs we investigated the role of the peripheral chemoreceptors in producing dynamic ventilatory (VE) responses to CO2. The immediate VE response, within 15 s, to transient CO2 inhalation was studied in two groups: 1) five lambs before carotid denervation and 2) the same lambs after carotid denervation. The time course of VE responses during the first 60 s after a step change to 8% inspired CO2 was also studied in lambs after carotid denervation and in a group of six carotid body-intact lambs 10-11 days of age. Acute CO2 responses were assessed using step changes to various concentrations of CO2 + air and CO2 + O2, while VE was recorded breath by breath. Intact lambs exhibited a brisk VE response to step changes in CO2, beginning after 3-5 s. Hyperoxia altered but did not suppress the dynamic VE CO2 response when the carotid chemoreceptors were intact. Carotid denervation markedly reduced the VE response during the first 25 s after a CO2 step change, revealing the time delay required for the central chemoreceptors to produce an effective VE response. The residual VE response remaining after CD was thought to be mediated by the remaining aortic body chemoreceptors and was eliminated by adding O2 to the CO2 challenges. However, after carotid denervation, even with CO2 + hyperoxia, the onset of a small tidal volume response was apparent by 10-12 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects on breathing of carotid body denervation in neonatal piglets.

The purpose of these studies was to test the hypothesis that carotid chemoreceptor activity is necessary for postnatal maturation of the ventilatory control system. By using a lateral surgical access, 17 piglets were carotid body denervated (CBD) and 14 were sham denervated at 3-25 days of age. After surgery, there was no irregular breathing in any group. There was no significant hypoventilation when CBD was performed at less than 5 days of age (n = 5) and only a mild (arterial PCO(2) 5 Torr; P < 0.05) to moderate, transient (arterial PCO(2) 8 Torr; P < 0.5) hypoventilation in piglets denervated at 10-15 (n = 6) and 20-25 (n = 6) days of age, respectively. Three weeks after surgery, both breathing of a hypoxic gas mixture and jugular venous NaCN injections elicited a hyperpnea in the CBD piglets that was attenuated compared with that in sham CBD piglets. In the CBD piglets, there was no response to injections of NaCN in the carotid arteries, but there was a response to NaCN injected into the proximal descending aorta, suggesting the residual peripheral chemosensitivity was of aortic origin. Carotid chemoreceptor-intact piglets had carotid and aortic NaCN chemosensitivity by 2 days of age. The carotid response persisted for the 40 days of the study, but the aortic reflex persisted only until approximately 8 days of age. We conclude that 1) the major effect of CBD per se in neonatal piglets is age-dependent hypoventilation and 2) there is a high degree of plasticity in peripheral chemosensitivity in neonates that may contribute to minimizing the changes in breathing after CBD.     

Postnatal maturation of vagal respiratory reflexes in preterm and full-term lambs.

The postnatal development of ventilatory reflexes originating from bronchopulmonary receptors was assessed in preterm vs. full-term lambs. Ventilation and arterial pressure were repeatedly measured in 10 preterm (gestational age, 132 days) and 7 full-term lambs without sedation from day 1 to day 42. The Hering-Breuer inhibitory reflex (slowly adapting stretch receptors) was assessed by the increase in expiratory time during end-inspiratory occlusion. The pulmonary chemoreflex (C-fiber endings) was assessed by the initial apnea + bradycardia + systemic hypotension and the secondary tachypnea after capsaicin intravenous injection. Results show the following. 1) Premature birth did not modify the maturation of the Hering-Breuer reflex. 2) Whereas a classic pulmonary chemoreflex was observed in the very first hours of life in preterm lambs, the tachypneic component of this reflex was weaker than in full-term lambs on day 1. 3) Premature birth led to a reversed postnatal maturation of this tachypneic response (tendency to increase with postnatal age). Our findings suggest that premature birth in lambs modifies postnatal maturation of the pulmonary chemoreflex.     

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 microg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO(2)). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated (P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation (P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses (P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.     

The reflex ventilatory responses of conscious, newborn rats to alternations of inspiratory oxygen concentration.

We examined the effect of a dynamic, hypoxic stimulus upon the reflex respiratory responses of 15, conscious rat pups on post-natal days 5-7 in order to ascertain the influence of a non-adapting peripheral chemoreceptor discharge upon respiratory control during hypoxia in the newborn. Respiration was measured as integrated airflow into and out of a body plethysmograph. The respiratory response to 6 minutes of a 16-breath cycle (approximately 5 s) in FiO2 between 0.21 and 0.10 (alternating hypoxia) was compared with the response to 6 min of a constant FiO2 of 0.12 (non-alternating hypoxia). Ventilation increased significantly from a control level of 0.12 +/- 0.02 ml/s (mean +/- SEM) to 0.18 +/- 0.02 and 0.17 +/- 0.02 ml/s in non-alternating and alternating hypoxia runs respectively during the first minute (phase 1) of each run, after which ventilation in both run types fell progressively and significantly back towards control levels to reach, by the sixth minute (phase 2), 0.13 +/- 0.01 and 0.12 +/- 0.02 ml/s respectively. No significant difference was found between the levels of ventilation in non-alternating hypoxia and alternating hypoxia during either phase 1 (P greater than 0.10) or phase 2 (P greater than 0.60). No significant alternation was found in any respiratory variable at the frequency of the 16-breath hypoxic cycle during either phase 1 or phase 2 of non-alternating hypoxia. However, a significant alternation, at this frequency, of 37 +/- 6% (P less than 0.05 compared to control) was found in ventilation during phase 1 of alternating hypoxia which was further increased to 62 +/- 8% (P less than 0.05 compared to phase 1) during phase 2. In phase 1 the alternation was due primarily to significant alternation in inspiratory time whilst in phase 2 significant alternation also occurred in tidal volume, expiratory time and mean inspiratory flow. Our results show that the magnitude of hypoxic ventilatory depression (HVD) in the newborn is not affected by an alternating hypoxic stimulus and that, during phase 2, ventilation can still be stimulated by peripheral chemoreceptors. We suggest that peripheral chemoreceptor adaptation is unlikely to be a major cause of HVD in the newborn rat and that the magnitude of HVD is, in part, the result of a competitive interaction between peripheral chemoreceptor stimulation and a centrally-mediated inhibitory action of hypoxia.     

Influence of carotid-denervation on the arousal and cardiopulmonary responses to alveolar hypercapnia in lambs

Experiments were done on five lambs to determine if carotid-denervation influences the arousal and cardiopulmonary responses to alveolar hypercapnia during sleep. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of systemic arterial blood pressure and arterial haemoglobin oxygen saturation. The carotid chemoreceptors and baroreceptors were denervated, a tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea so that the inspired gas mixture could be changed quickly. No sooner than three days after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing room air and during experimental periods of alveolar hypercapnia when the lamb was breathing 10% carbon dioxide in air. Alveolar hypercapnia was terminated during an experimental period by changing the gas mixture back to room air once the animal aroused from sleep. If an animal did not arouse within 2 min, the gas mixture was changed back to room air. Arousal occurred during only 6 of 12 epochs in quiet sleep and during only 2 of 10 epochs in active sleep. These data provide evidence that the carotid chemoreceptors and/or carotid baroreceptors play a major role in causing arousal from sleep during alveolar hypercapnia in lambs.     

Effects of carotid and aortic chemoreceptor denervation in newborn piglets.

The objective of the present study was to test the hypothesis that in neonatal piglets there would be no hypoventilation after sham denervation or aortic denervation (AOD) alone, but there would be transient hypoventilation after carotid body denervation (CBD) and the hypoventilation would be greatest after combined carotid and aortic denervation (CBD+AOD). There was a significant (P < 0.05) hypoventilation in CBD and CBD+AOD piglets denervated at 5, 15, and 25 days of age. The hypoventilation in CBD+AOD piglets denervated at 5 days of age was greater (P < 0.05) than that of all other groups. Conversely, sham-denervated and AOD piglets did not hypoventilate after denervation. Injections of sodium cyanide showed that aortic chemoreceptors were a site of recovery of peripheral chemosensitivity after CBD. This aortic sodium cyanide response was abolished by prior injection of a serotonin 5a receptor blocker. Residual peripheral chemosensitivity after CBD+AOD was localized to the left ventricle. We conclude that 1) aortic chemoreceptors contribute to eupneic breathing in piglets that were carotid denervated at 5 days of age and 2) there are multiple sites of residual peripheral chemosensitivity after CBD.     

Re-setting of the hypoxic sensitivity of aortic chemoreceptors in the new-born lamb

We tested to see whether the steady-state hypoxic sensitivity of aortic chemoreceptors was re-set during the first 2-3 weeks of post-natal life. Aortic chemo-receptor activity was recorded from the distal end of the cut aortic branch of the cervical vagus in pentobarbitone - anesthetized, new-born lambs. Two groups were studied, the first aged 1-4 days and the second aged 10-19 days. Chemoreceptor discharge increased as hyperbolic function with increasing isocapnic hypoxia in both groups and we quantified the position and the shape of this response curve. It was shifted to the right significantly in the older group of lambs, the mean vertical asymtote increasing from 10.00 to 27.95 torr PO2. No significant difference was found in the horizontal asymotote or in the 'shaping term' between the two groups. The greatest differences between the stimulus-response curves of the two groups of animals with respect to the mean level of discharge and the slope of the curve occurred when PaO2 was below ca. 50 torr. The aortic chemoreceptors of older lambs were unable to maintain a sustained discharge at arterial PO2 values below ca. 30 torr. In contrast, in the younger group PO2 often had to be reduced below this level before discharge increased significantly. We conclude that, like the carotid chemoreceptors, aortic chemoreceptor sensitivity is re-set over the first few weeks of life. The re-setting may contribute to the increase in the ventilatory response to hypoxia which occurs over this period.     

Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0-5 and 6-13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.     

Central neural respiratory response to carotid sinus nerve stimulation in newborns

During exposure to hypoxia newborns hypoventilate following a brief period of hyperventilation. Failure of integration of the afferent signals from peripheral O2 chemoreceptors due to immaturity of the central respiratory centers could explain this paradoxical respiratory response. To test this hypothesis we have utilized anesthetized, paralyzed, mechanically ventilated newborn piglets and lambs (less than 11 days) and old piglets (19-35 days). The vagus nerves were cut in each animal. Respiratory activity was quantified by integration of phrenic neural activity. A carotid sinus nerve (CSN) was isolated and electrically stimulated for periods of 1-6 min. In all three groups of animals respiratory activity was continuously elevated throughout the period of CSN stimulation. After CSN stimulation respiratory activity immediately declined about 25% from the stimulated value. Thereafter respiratory activity declined in an exponential fashion toward the initial control level of respiratory activity. The time constant of this latter decay was 84.2 s in the young piglets, 83.2 s in the old piglets, and 63.0 s in the lambs. These results indicate that the respiratory centers of newborn piglets and lambs can maintain integration of continuous afferent CSN activity. Further, the respiratory afterdischarge that follows CSN stimulus cessation is similar to that of adults. These studies indicate that, during periods of O2 sufficiency, the central respiratory centers of newborns respond in a qualitatively similar manner to CSN stimulation as do adult cats.     

Chemoreceptor and vagal influences on thyroarytenoid muscle activity in awake lambs during hypoxia.

This study was designed to identify the various controllers of thyroarytenoid (TA) activity in lambs during resting breathing, hypocapnic hypoxia, and isocapnic hypoxia. The TA muscle is known as the major adductor of the laryngeal aperture. We assumed that both the chemoreceptors and vagal nerves would interact to inhibit TA activity during hypoxia and to favor the occurrence of hyperpnea as a defense against hypoxia. We recorded TA activity directly in 11 awake lambs, aged 11 to 22 days, and studied them in three groups: four normals, four carotid body denervated, and three vagotomized. To test the contribution of the chemoreceptors to TA activity, we used pure O2 tests (Dejours' test) to silence the effects of the peripheral arterial chemoreceptors on the larynx during resting breathing and during the course of two hypoxia tests (the first: hypocapnic hypoxia; the second: isocapnic hypoxia). Our results confirmed 1) that both the peripheral arterial chemoreceptors and the vagal nerves inhibit the TA activity of 15-day-old lambs, during both resting and hypocapnic hypoxia conditions, and 2) that their effects override the hypocapnic effects that would otherwise recruit the TA muscle and close the glottis during hypocapnic hypoxia. We also found that vagotomy, or the pure O2 test, causes major recruitment of TA activity. These findings confirm that 15-day-old lambs are capable of using sustained hyperventilation as a means of fighting hypoxia, and that, because of the control of both the vagus nerves and the chemoreceptors, the laryngeal dynamic is able to keep the glottis aperture actively open, thereby favoring the hyperpnea.     

Influence of the stimulation of central chemoreceptors on the gastric mucosal blood flow in artificially ventilated and spontaneously breathing rats.

Respiratory failure coincides frequently with the occurrence of gastric ulceration. In advanced respiratory insufficiency hypoxemia is often accompanied by hypercapnia, which is the stimulus for central chemoreceptors as well as for carotid body chemoreceptors. The purpose of the work was to investigate the reflex effect of stimulation of central chemoreceptors on gastric mucosal blood flow (GMBF) in the rat. Central chemoreceptors were stimulated by a gas mixture composed of 10% carbon dioxide, 50% oxide and 40% nitrogen. In artificially ventilated and spontaneously breathing animals, the stimulation of central chemoreceptors caused a significant increase in gastric mucosal vascular resistance, accompanied by a marked decline in blood flow. We hypothesize that in patients with respiratory insufficiency accompanied by hypercapnia, the reflex impairment of GMBF may contribute to gastric ulceration.     

Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs.

The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2-3, 14-16, and 21-22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5-7 min each to a maximum 7-8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth.     

Consequences of capsaicin treatment on pulmonary vagal reflexes and chemoreceptor activity in lambs.

The aim of this study was to test the hypothesis that capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function but does not alter other vagal pulmonary receptor functions or peripheral and central chemoreceptor functions. Eleven lambs were randomized to receive a subcutaneous injection of either 25 mg/kg capsaicin (6 lambs) or solvent (5 lambs) under general anesthesia. Capsaicin-treated lambs did not demonstrate the classical ventilatory response consistently observed in response to capsaicin bolus intravenous injection in control lambs. Moreover, the ventilatory responses to stimulation of the rapidly adapting pulmonary stretch receptors (intratracheal water instillation) and slowly adapting pulmonary stretch receptors (Hering-Breuer inflation reflex) were similar in both groups of lambs. Finally, the ventilatory responses to various stimuli and depressants of carotid body activity and to central chemoreceptor stimulation (CO(2) rebreathing) were identical in control and capsaicin-treated lambs. We conclude that 25 mg/kg capsaicin treatment in lambs selectively inhibits bronchopulmonary C-fiber function without significantly affecting the other vagal pulmonary receptor functions or that of peripheral and central chemoreceptors.     

The essential role of carotid body chemoreceptors in sleep apnea

Sleep apnea is attributable, in part, to an unstable ventilatory control system and specifically to a narrowed "CO2 reserve" (i.e., the difference in P(a)CO2 between eupnea and the apneic threshold). Findings from sleeping animal preparations with denervated carotid chemoreceptors or vascularly isolated, perfused carotid chemoreceptors demonstrate the critical importance of peripheral chemoreceptors to the ventilatory responses to dynamic changes in P(a)CO2. Specifically, (i) carotid body denervation prevented the apnea and periodic breathing that normally follow transient ventilatory overshoots; (ii) the CO2 reserve for peripheral chemoreceptors was about one half that for brain chemoreceptors; and (iii) hypocapnia isolated to the carotid chemoreceptors caused hypoventilation that persisted over time despite a concomitant, progressive brain respiratory acidosis. Observations in both humans and animals are cited to demonstrate the marked plasticity of the CO2 reserve and, therefore, the propensity for apneas and periodic breathing, in response to changing background ventilatory stimuli.     

Postnatal maturation of respiration in intact and carotid body-chemodenervated lambs

The contribution of the carotid body chemoreceptor to postnatal maturation of breathing was evaluated in lambs from 7 to 70 days of age. The study was conducted by comparing the eupneic ventilation and resting pneumograms in intact conscious lambs with those of lambs that were carotid body chemodenervated (CBD) at birth. In comparison to the 1-wk-old intact lambs, the CBD lambs had significant decreases in minute ventilation (VE, 313 vs. 517 ml/kg), tidal volume (VT, 7.2 vs. 10.5 ml/kg), respiratory rate (f, 44 vs. 51 breaths/min), and occlusion pressure (P0.1, 2.8 vs. 7.2 cmH2O). Arterial PO2's were 59 vs. 75 Torr (P less than 0.05) and arterial PCO2's 47 vs. 36 Torr (P less than 0.05), respectively, in CBD and intact lambs. In intact lambs from 7 to 70 days, resting VE decreased progressively from 517 to 274 ml/kg (P less than 0.01) due to a fall in VT, mean inspiratory flow (VT/TI), and f, whereas the ratio of inspiratory time to total breath duration remained constant. P0.1 decreased from 7.2 to 3.9 cmH2O from 7 to 42 days. In contrast the CBD lambs experienced only minimal changes in VE, VT, VT/TI, and f during the same period. VE only decreased from 313 to 218 and P0.1 from 2.8 to 2.4 cmH2O. In contrast to that of intact lambs the resting pneumogram of CBD lambs remained relatively fixed from 7 to 70 days. Three CBD lambs died unexpectedly, without apparent cause, in the 4th and 5th wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory function in lambs after in utero treatment of lung hypoplasia by tracheal obstruction.

Tracheal obstruction (TO) stimulates growth of hypoplastic lungs in the fetus, but there is little knowledge of subsequent postnatal respiratory function. We have determined the effectiveness of TO in fetal sheep with existing lung hypoplasia in restoring postnatal respiratory function. Lung hypoplasia was induced by lung liquid drainage from 112 days of gestation to term ( approximately 148 days). We used an untreated group (ULH), a treated group (TLH) in which the trachea was obstructed for 10 days, and a control group. ULH lambs died within 4 h of birth. TLH lambs were hypoxic for the first week and were hypercapic at 2 days. Pulmonary diffusing capacity, gas volumes, and respiratory compliances were not different between control and TLH lambs. Minute ventilation was not different between the two groups; however, tidal volumes were lower and respiratory frequencies were higher in TLH lambs than in controls for 2 wk after birth. We conclude that 10 days of TO in the presence of initial lung hypoplasia prevents death at birth and returns most aspects of pulmonary function to normal by 1-2 wk after birth.     

Stimulation of fetal breathing activity by beta-adrenergic mechanisms

Experiments were done on chronically prepared fetal lambs, 125-135 days gestation, to test the effects of various catecholamines on fetal breathing (FB) as well as the influence of isoproterenol on the fetal respiratory response to hypoxemia. Bolus injections of epinephrine, norepinephrine, and isoproterenol (5-20 micrograms) were administered via the lingual artery or femoral or jugular vein during periods of FB activity or apnea. The effects of epinephrine and norepinephrine on FB were variable and not statistically significant. Isoproterenol produced a significant increase in FB, frequency of breathing, and mean inspiratory effort, when infused during rapid-eye-movement (REM) sleep but it failed to induce FB during non-rapid-eye-movement (NREM) sleep. The positive response during REM sleep was absent following pretreatment with 3-5 mg propranolol and after bilateral section of the sinus nerves. The effect of hypoxia on FB was tested before and during constant infusion of isoproterenol (1 microgram/min iv). A reduction of the fetal arterial PO2 by 3-10 Torr produced the characteristic depression of FB in either situation. These results indicate that the fetal carotid body chemoreceptors can reflexly stimulate FB under certain circumstances but that their effectiveness is limited by more powerful inhibitory mechanisms such as those operative during NREM sleep and hypoxemia.     

Response of newborn lambs to CO-induced hypoxia

This study was undertaken to measure the neonate's response to CO-induced hypoxia in the first 10 days of life. CO breathing was used to induce hypoxia because CO causes tissue hypoxia with no or minimal chemoreceptor stimulation. An inspired gas mixture of 0.25 to 0.5% CO in air was used to raise the blood carboxyhemoglobin (HbCO) progressively from 0 to 60% over approximately 20 min. The study, conducted in awake conscious lambs aged 2 and 10 days, consisted in measuring the response of ventilation and the change in arterial blood gases during the rise of HbCO. The results showed that the 2- and 10-day-old lambs tolerated very high HbCO levels without an increase in minute ventilation (VE) and without metabolic acidosis. At both ages, HbCO caused no VE change until HbCO levels rose to between 45 and 50% after which the VE change was exponential in some animals but minimal in others. The VE change was brought about by a rise in tidal volume and respiratory frequency. During the period of maturation from 2 to 10 days, there was a small shift to the right in the VE-HbCO response. In the 10-day-old lambs the VE response to high HbCO was greater than that of the 2-day-olds because of the lambs' higher respiratory frequency response. Six of the 10-day-old lambs but only two of the 2-day-old lambs showed a hypoxic tachypnea to HbCO of 55-65%. None of the lambs developed periodic breathing, dysrhythmic breathing, or recurrent apneas with an HbCO level as high as 60%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preterm birth in lambs: sleep patterns and cardio-respiratory changes.

Cardio-respiratory physiology in sleep was examined in eight preterm lambs born at 133-135 (134 +/- 1, mean SEM) days of gestation after 3-5 days of pulsatile ACTH/TRH infusion, and contrasted with eight lambs born at term (147 +/- 1 days). Lambs were instrumented with electrodes for recording electrocorticogram, electro-oculogram and nuchal electromyogram to define behavioural states, as well as carotid arterial catheters for determination of arterial pressure, heart rate and arterial blood gases. Compared to full-term lambs, the preterm lambs exhibited extended active sleep times, elevated PaCO2 and faster heart rate in all behavioural states than full-term lambs; with increasing postnatal age, sleep times and heart rate declined. As similar differences are found in preterm human infants, the preterm lamb will be a useful model to study the underlying physiology of these cardio-respiratory alterations.