Effect of dopamine on hypoxic ventilatory response of sedated piglets with intact and denervated carotid bodies.

To determine whether the neonatal hypoxic ventilatory depression is in part produced by an increased endogenous dopamine release that can depress the activity of central and peripheral chemoreceptors, 31 sedated and spontaneously breathing newborn piglets [age 5 +/- 1 (SD) days; weight 1.7 +/- 0.4 kg] were randomly assigned to an intact carotid body or a chemodenervated group. Minute ventilation (VE), arterial blood pressure, and cardiac output (CO) were measured in room air before infusion of saline or the dopamine antagonist flupentixol (0.2 mg/kg i.v.) and 15 min after drug infusion and were repeated after 10 min of hypoxia (inspiratory O2 fraction = 0.10). VE increased significantly after 10 min of hypoxia in the piglets that received flupentixol independent of whether the carotid bodies were intact or denervated. However, the increase in VE was largest and sustained throughout the 10 min of hypoxia only in the intact carotid body flupentixol group. As expected, the initial increase in VE with hypoxia was abolished by carotid body denervation. Changes in arterial blood gases, CO, and mean arterial blood pressure with hypoxia were not different among groups. These results demonstrate that flupentixol reverses the late hypoxic decrease in VE, acting through peripheral and central dopamine receptors. This effect is not related to changes in cardiovascular function or acid-base status.

Effects of GABA receptor blockage on the respiratory response to hypoxia in sedated newborn piglets.

Brain gamma-aminobutyric acid (GABA) levels increase during hypoxia, which may modulate the ventilatory response to hypoxia. To test the possibility that the depressed neonatal ventilatory response to hypoxia may be related to increased central nervous system GABA activity, 26 sedated spontaneously breathing newborn piglets (age 5 +/- 1 day, wt 1.7 +/- 0.4 kg) were studied. Minute ventilation (VE), oxygen consumption, heart rate, arterial blood pressure, and arterial blood gases were measured in room air and after 1, 5, and 10 min of hypoxia (inspired O2 fraction 0.10) before drug intervention. Immediately after these measurements, an infusion of saline or the GABA alpha-receptor blocker (bicuculline, 0.3 mg/kg iv) or beta-receptor blocker (CGP-35348, 100-300 mg/kg iv) was administered while animals were hypoxic. All measurements were repeated at 1, 5, and 10 min after initiation of the drug infusion. Basal VE was similar among groups. During hypoxia, VE increased significantly in the animals that received either a GABA alpha- or beta-receptor blocker but not in those receiving saline. Changes in arterial Po2, oxygen consumption, heart rate, and arterial blood pressure were similar among groups before and after saline or GABA antagonist infusion. These results suggest that the decrease in ventilation during the biphasic ventilatory response to hypoxia in the neonatal piglet is in part mediated through the depressant effect of GABA on the central nervous system.

Effect of N-methyl-D-aspartate-receptor blockade on hypoxic ventilatory response in unanesthetized piglets.

The central excitatory amino acid (EAA) neurotransmitter glutamate has been shown to mediate the ventilatory response to hypoxia through N-methyl-D-aspartate (NMDA) receptors in anesthetized adult animals. To determine the role of the EAA glutamate in the neonatal ventilatory response to hypoxia, 19 unanesthetized chronically instrumented piglets were studied. Minute ventilation (VE), oxygen consumption (VO2), arterial blood pressure (ABP), heart rate (HR), and blood gases were measured in room air (RA) and after 1, 5, and 10 min of hypoxia (inspired oxygen fraction = 0.10) before and after an infusion of saline or CGS-19755, a competitive NMDA-receptor blocker (10 mg/kg i.v.). Nine control piglets [age 6 +/- 1 (SD) days; weight 2.02 +/- 0.40 kg] and 10 CGS-19755-treated animals (age 6 +/- 1 days; weight 1.90 +/- 0.66 kg) were studied during quiet sleep and in a thermoneutral environment. There was a marked decrease in the VE response to hypoxia after the administration of CGS-19755. The ventilatory response to hypoxia was not modified by saline infusion. Changes in ABP and arterial PO2 during hypoxia were similar between groups, whereas the decrease in arterial PCO2 was significantly less after CGS-19755 administration. The increase in HR with hypoxia was eliminated by the NMDA-receptor blocker administration. VO2 decreased with hypoxia in both groups, but this decrease was more marked after the NMDA-receptor blockade. These results suggest that the central EAA glutamate mediates, at least in part, the hypoxic hyperventilation in unanesthetized newborn piglets.

Depressed ventilatory response to hypoxia in hypothermic newborn piglets: role of glutamate.

To evaluate whether changes in extracellular glutamate (Glu) levels in the central nervous system could explain the depressed hypoxic ventilatory response in hypothermic neonates, 12 anesthetized, paralyzed, and mechanically ventilated piglets <7 days old were studied. The Glu levels in the nucleus tractus solitarius obtained by microdialysis, minute phrenic output (MPO), O2 consumption, arterial blood pressure, heart rate, and arterial blood gases were measured in room air and during 15 min of isocapnic hypoxia (inspired O2 fraction = 0.10) at brain temperatures of 39.0 +/- 0.5 degrees C [normothermia (NT)] and 35.0 +/- 0.5 degrees C [hypothermia (HT)]. During NT, MPO increased significantly during hypoxia and remained above baseline. However, during HT, there was a marked decrease in MPO during hypoxia (NT vs. HT, P < 0.03). Glu levels increased significantly in hypoxia during NT; however, this increase was eliminated during HT (P < 0.02). A significant linear correlation was observed between the changes in MPO and Glu levels during hypoxia (r = 0.61, P < 0.0001). Changes in pH, arterial PO2, O2 consumption, arterial blood pressure, and heart rate during hypoxia were not different between the NT and HT groups. These results suggest that the depressed ventilatory response to hypoxia observed during HT is centrally mediated and in part related to a decrease in Glu concentration in the nucleus tractus solitarius.

Pulmonary mechanics in normal infants and young children during first 5 years of life.

To characterize lung function in young children we measured lung compliance and pulmonary conductance in 40 normal infants and children ranging in age from the newborn period to 5 years. Inspiratory and expiratory flow was measured by a pneumotachograph, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a N2 washout technique. The esophageal pressure change per breath [(mean +/- SD) 7.3 +/- 1.4 cm H2O] and specific compliance (75 +/- 13 ml/cm H2O/L-FRC) did not change with growth. Specific conductance was high (0.60 L/s/cm H2O/L-FRC) in preterm infants, decreasing rapidly with initial growth but minimally beyond 10 kg of body weight, and stabilizing at 0.10 L/s/cm H2O/L-FRC. During the age period studied, compliance increased approximately x 25 whereas conductance only rose five-fold. The changes in compliance and conductance were well correlated to FRC, body weight, and length. These findings suggest that in the last trimester of pregnancy the airways are already well developed and postnatal lung growth occurs mainly by formation of new alveoli, leading to a proportional increase in FRC and lung compliance. Postnatally, conductance increases much more slowly than FRC, resulting in a rapid drop in specific conductance.

Effect of a beta-agonist nebulization on lung function in neonates with increased pulmonary resistance.

Pulmonary resistance is elevated early in preterm infants who later develop chronic lung disease. This early increase in pulmonary resistance may play a role in the development of severe bronchopulmonary dysplasia (BPD). A beta-2-agonist (isoetharine HCl) was used as an aerosol in 13 preterm infants with elevated pulmonary resistance. Their birthweight ranged from 880 to 1630 g, their gestational age from 27 to 34 weeks, and their post natal age from 3 to 18 days. All infants had required mechanical ventilation for respiratory distress syndrome and therefore were at risk to develop BPD. Pulmonary mechanics were measured before and 30 minutes after aerosol treatment, determining inspiratory and expiratory flow with a pneumotachometer and esophageal pressure through a water-filled feeding tube. The treatment was well tolerated with no significant changes in blood pressure, heart rate, or respiratory rate. Pulmonary resistance decreased significantly from 130 +/- 35 cm H2O/L/sec to 89 +/- 24 cm H2O/L/sec after the treatment. Dynamic lung compliance increased in 11 of the 13 infants. It is concluded that beta-2-agonist nebulization is effective in reducing the early increase in pulmonary resistance that occurs in preterm infants who are at risk of developing BPD. This effect may be due to relaxation of bronchial smooth muscle, to improved mucociliary transport, and to a reduction in peribronchial edema.

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system.

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT(1) receptor (AT(1)-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO(2) = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT(1)-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT(1)-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT(1)-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT(1)-R staining, but C animals showed weak iNOS and AT(1)-R staining. Macrophages of L and P animals showed moderate and weak AT(2)-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT(1)-R blockade. We suggest that AT(1)-R blockade might act through AT(2)-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Brain blood flow and ventilatory response to hypoxia in sedated newborn piglets.

To evaluate the relationship between brain blood flow and ventilatory response to hypoxia, seventeen sedated, spontaneously breathing newborn piglets were studied. Minute ventilation (VE) was measured by pneumotachograph, cardiac output by thermodilution and total brain and brain stem blood flows with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Two patterns of ventilatory response to hypoxia were observed in the study animals. All animals increased VE during the 1st min of hypoxia, but nine (mean +/- SD; age 5 +/- 1.3 d; wt 1828 +/- 437 g) sustained increased VE after 10 min of hypoxia (increases VE group). The remaining eight animals (age 5 +/- 1.2 d; wt 1751 +/- 168 g) had decreased VE at 10 min of hypoxia to values less than their room air baseline (decreases VE group). The decrease in PaO2 during hypoxia was similar in both groups, however the PaCO2 decreased significantly only in the increases VE group. Although cardiac output increased significantly during hypoxia in both groups, the values during normoxia and hypoxia were lower in the decreases VE group (p less than 0.001). Arterial blood pressure increased significantly during hypoxia only in the increases VE group. The increase in total brain and brain stem blood flows with hypoxia was similar in both groups, despite the two different patterns of ventilatory response to hypoxia. These data suggest that in this animal model the distinct patterns of ventilatory response to hypoxia are not related to the changes in total brain or brain stem blood flows that occur during hypoxia.

Effects of epinephrine on the cardiorespiratory response to hypoxia in sedated newborn piglets with intact and denervated carotid bodies.

In order to evaluate the effects of epinephrine on the cardiorespiratory response to hypoxia in the neonate, 35 sedated, spontaneously breathing newborn piglets (mean +/- SD, age 5 +/- 0.8 days; weight 1.6 +/- 0.3 kg) with intact (ICB) or denervated (DCB) carotid bodies were studied before and during an infusion of saline or epinephrine (2.2 +/- 1.0 microgram/kg/min, i.v.). Cardiorespiratory measurements were performed while the animals breathed room air and after 10 min of hypoxia (FiO2 0.10) during saline or epinephrine infusion. During epinephrine infusion, the ICB animals had a sustained increase in minute ventilation during hypoxia while the control group showed a biphasic ventilatory response with depression during sustained hypoxia. After the chemodenervation, the ventilatory response to hypoxia was completely blunted in saline and epinephrine animals. In the ICB and DCB animals, the arterial blood pressure decreased significantly with hypoxia during epinephrine infusion, while cardiac output increased significantly in all ICB and DCB saline animals. The oxygen consumption (VO2) decreased significantly after 10 min of hypoxia in all groups except in the ICB epinephrine animals, in whom the VO2 did not change with hypoxia. In conclusion, the administration of epinephrine to newborn piglets reverses the depressed ventilatory response to hypoxia and this effect requires the activity of the peripheral chemoreceptors.

A simple method for measuring functional residual capacity by N2 washout in small animals and newborn infants.

An open circuit N2 washout technique is described for the determination of functional residual capacity in infants. Either 100% O2 or any oxygen/helium mixture can be used as the washing gas. The subject breathes the washing gas through a T-tube and the washed out nitrogen is mixed with this gas in a mixing chamber, placed into the exhalation part of the circuit. The N2 concentration of the mixed gas is analyzed continuously, and the concentration signal is electronically integrated over time. Calibration of the system is accomplished by injecting known amounts of nitrogen or room air into the circuit. The gas flow through the system must remain constant and is adjusted to approximate peak inspiratory flow of the infant. In vitro testing of the system showed that the technique gives reproducible values (coefficient of variance less than 1.0%) and that the integrated signal output has a close linear correlation with the amount of N2 washed out (r = 0.99). In vivo measurements in 10 cats confirmed the accuracy and reproducibility of the method when compared with N2 collection. The technical advantages of the system are simplicity of components, absence of valves, easy calibration, low dead space, and no need to collect or measure expired gases. For the infant this means no added resistance during washout and no risk of hypoxia, hyperoxia, or hypercapnea. In the presence of pulmonary disease and poor gas mixing the washout period can be prolonged as needed. There is no lower limit of weight or size for functional residual capacity measurements in small infants or animals.

Effect of alpha adrenergic blockade on brain blood flow and ventilation during hypoxia in newborn piglets.

The influence of cardiovascular changes on ventilation has been demonstrated in adult animals and humans (Jones, French, Weissman & Wasserman, 1981; Wasserman, Whipp & Castagna 1974). It has been suggested that neonatal hypoxic ventilatory depression may be related to some of the hemodynamic changes that occur during hypoxia (Brown & Lawson, 1988; Darnall, 1985; Suguihara, Bancalari, Bancalari, Hehre & Gerhardt, 1986). To test the possible relationship between the cardiovascular and ventilatory response to hypoxia in the newborn, eleven sedated spontaneously breathing piglets (age: 5.9 +/- 1.6 days; weight: 1795 +/- 317 g; SD) were studied before and after alpha adrenergic blockade with phenoxybenzamine. Minute ventilation (VE) was measured with a pneumotachograph, cardiac output (CO) by thermodilution and total and regional brain blood flow (BBF) with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Hypoxia was again induced one hour after infusion of phenoxybenzamine (6 mg/kg over 30 min). After 10 min of hypoxia, in the absence of phenoxybenzamine, the animals responded with marked increases in VE (P less than 0.001), CO (P less than 0.001), BBF, and brain stem blood flow (BSBF) (P less than 0.02). However, the normal hemodynamic response to hypoxia was eliminated after alpha adrenergic blockade. There were significant decreases in systemic arterial blood pressure, CO, and BBF during hypoxia after phenoxybenzamine infusion; nevertheless, VE increased significantly (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Serial determination of pulmonary function in infants with chronic lung disease.

Pulmonary function was measured in 39 infants with chronic lung disease who had required mechanical ventilation starting during the first week of life for a median of 9 days (range 1 to 46 days) and supplemental oxygen for a median of 48 days (range 28-162 days). Their mean birth weight was 1140 g (range 550 to 2325 g), and mean gestational age 29.8 weeks (range 26 to 37 weeks). Ventilation was measured by pneumotachography, esophageal pressure through a water-filled feeding tube, and functional residual capacity (FRC) by a modified nitrogen washout technique. Lung compliance, pulmonary conductance, and FRC were determined at 1, 3, 6, 12, 18, 24, and 36 months after birth. Pulmonary function was also determined in 40 normal children, ranging in age from neonates to 5 years, who served as controls. In infants with chronic lung disease, growth in weight and length followed the 10th to 25th percentiles of the normal curve. Minute ventilation and respiratory effort remained elevated throughout the follow-up. FRC per kilogram of body weight was decreased at 1, 3, and 6 months after birth, but thereafter was in the normal range. FRC increased in proportion to weight at the same rate as in the controls. Lung compliance was only half of normal at 1 month, increased with growth in close correlation with weight, and was approximately 80% of normal at the end of follow-up. Pulmonary conductance was 50% of normal at 1 month, increased little during the first 6 months, but reached 85% of normal at 3 years of age. There was no evidence of gas trapping. These results indicate that in infants with chronic lung disease after mechanical ventilation, lung volume increases normally, probably by formation of new alveoli, which also leads to improvement in lung compliance. Airway growth is slow during the first 6 months after birth, but the subsequent faster growth leads to conductance values close to normal at 3 years of age.

Effect of distal endotracheal bias flow on PaCO2 during high frequency oscillatory ventilation.

In order to evaluate the effect of distal endotracheal bias flow during HFOV on PaCO2 we studied adult rabbits with normal lungs and those who had meconium-induced lung dysfunction. Animals were studied while 1.0, 1.4 and 1.8 ml/kg tidal volumes (VT) were delivered by a high frequency oscillator. In animals with normal lungs and a 1.0 liter/min distal bias flow, the PaCO2 decreased significantly (p less than 0.01) with all VT used. In animals with meconium instillation the decrease in PaCO2 was also significant (p less than 0.05) at all combinations of VT and distal bias flow. The higher the distal bias flow the more pronounced was the lowering effect on PaCO2. We conclude that during HFOV it is possible to improve CO2 elimination using small additional bias flow delivered near the tip of the endotracheal tube in animals with normal abnormal lung function. This may allow adequate alveolar ventilation with even smaller VT, thus reducing the risk of barotrauma.

Effect of cyclooxygenase inhibition on retinal and choroidal blood flow during hypercarbia in newborn piglets.

The effect of the cyclooxygenase inhibitor, indomethacin, on choroidal (ChBF) and retinal (RBF) blood flow during hypercarbia was examined in 16 paralyzed and mechanically ventilated piglets less than 8 d old. The animals were randomly assigned to a control group (mean +/- SEM: wt, 1.66 +/- 0.1 kg; n = 8) that received a placebo infusion or to an indomethacin treatment group (wt, 1.68 +/- 0.2 kg; n = 8) that received an infusion of indomethacin (5 mg/kg i.v. over 30 min). Baseline ChBF and RBF were measured using radiolabeled microspheres in room air before and 15 min after the administration of placebo or indomethacin. Animals were then exposed to 30 min of hypercarbia (6-7% CO2, arterial CO2 pressure 8-10 kPa) and measurements were repeated. There were no significant differences in RBF between control (40 +/- 3 mL/min/100 g) and indomethacin-treated animals (40 +/- 3 mL/min/100 g) before administration of placebo or indomethacin. However, RBF decreased significantly in the indomethacin-treated animals (28 +/- 2 mL/min/100 g) compared to the control group (42 +/- 4 mL/min/100 g) 15 min after administration of placebo or indomethacin. Furthermore, an increase in RBF occurred during hypercarbia in the control group (86 +/- 6 mL/min/100 g), but this change was blunted in the indomethacin-treated animals (33 +/- 5 mL/min/100 g) (p less than 0.001). In contrast, ChBF did not differ significantly between the control and indomethacin groups during the periods studied. These results suggest that the increase in RBF during hypercarbia is at least partially mediated by cyclooxygenase by-products of arachidonic acid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic and ventilatory effects of high-frequency jet and conventional ventilation in piglets with lung lavage.

The cardiovascular and ventilatory effects of high-frequency jet ventilation (HFJV) and conventional ventilation (CV) were evaluated in a saline lung lavage model in piglets. After saline lavage and stabilization on CV, animals were randomized to either mode of ventilation for 4 h. Arterial blood gases, cardiac output, mean pulmonary and arterial blood pressures, and pulmonary and systemic vascular resistances were compared between groups. Alveolar-arterial oxygen gradient (AaDO2) was lower in the HFJV than in the CV group after 3 h of ventilation (p less than 0.04). The peak inspiratory pressure necessary to maintain PaCO2 within the normal range was approximately half as much in the HFJV group as in the CV group (p less than 0.005) throughout the entire study period. Mean airway pressure, cardiac output, mean pulmonary and arterial blood pressures as well as pulmonary and systemic vascular resistances were not statistically different between groups. These results suggest that in this model, HFJV produces better oxygenation with lower peak airway pressures compared to CV without producing hemodynamic compromise.

Effects of chloral hydrate on the cardiorespiratory response to hypoxia in newborn piglets.

To assess the effects of chloral hydrate (CH) on the cardiorespiratory response to hypoxia in the neonate, 17 newborn piglets were chronically instrumented 48-72 h before study and randomly assigned to a CH group (100 mg/kg, i.p.) or saline group. The animals were intubated and studied under quiet sleep which was determined by behavioral states, and continuous electro-oculographic and electroencephalographic monitoring. Minute ventilation (VE), tidal volume, respiratory rate, arterial blood gases (ABG), oxygen consumption (VO2), arterial blood pressure (ABP) and heart rate (HR) were measured before and after CH or saline administration during room air and after 10 min of hypoxia (fraction of inspired oxygen concentration = 0.10). Cardiorespiratory response to hypoxia was similar before and after saline infusion. Basal VE and the ventilatory response to hypoxia were similar before and after CH administration. In contrast, the basal ABP decreased significantly (p < 0.05) after CH administration, but the ABP response to hypoxia was similar before and after CH. A significant increase in both basal HR and HR with hypoxia was observed after CH administration. In addition, VO2 and ABG were not modified by CH treatment during normoxia and hypoxia. These data demonstrate that a sedative dose of CH does not significantly modify the ventilatory response to hypoxia in newborn piglets. However, CH produced some changes in the cardiovascular system which should be considered when using it in infants with hemodynamic derangements.

Effect of L-aspartate on the ventilatory response to hypoxia in sedated newborn piglets.

L-aspartate (L-ASP) acts as an excitatory amino acid neurotransmitter at the synapses of brain stem respiratory neurons. In order to determine the effect of L-ASP on the neonatal ventilatory response to hypoxia, 9 control piglets [age 4.3 +/- (SD) 0.9 days, weight 1.9 +/- 0.5 kg] and 9 L-ASP-treated animals [age 5.0 +/- (SD) 1.4 days, weight 2.1 +/- 0.7 kg] were studied. Minute ventilation, oxygen consumption, arterial blood pressure, and blood gases were measured in sedated piglets while spontaneously breathing room air and during 1, 5, and 10 min of hypoxia (O2 concentration in inspired gas 0.10). Measurements were obtained before and 60 min after the administration of L-ASP (580 mg/kg i.v. over 1 h) or 5% dextrose solution. In the control animals, the ventilatory response to hypoxia was similar before and after dextrose infusion. In contrast, a significant and sustained increase in ventilation was observed at 1, 5, and 10 min of hypoxia after the administration of L-ASP. Changes in oxygen consumption, heart rate, arterial blood pressure, pH, and arterial O2 tension with hypoxia were similar before and after the L-ASP infusion, while the arterial CO2 tension decreased significantly during hypoxia after the administration of L-ASP. These data suggest that the excitatory amino acid L-ASP is an important mediator of the hypoxic hyperventilation in the neonate. We speculate that the administration of exogenous L-ASP modifies the balance of central nervous system neurotransmitters during hypoxia, resulting in predominance of excitatory neurotransmission.

Changes in ventilation and oxygen consumption during acute hypoxia in sedated newborn piglets.

The purpose of this study was to evaluate the relationship between changes in minute ventilation (VE) and oxygen consumption (VO2) in response to acute hypoxia in the newborn piglet. Twenty-five (mean +/- SD; age, 4.7 +/- 1.1 d; weight, 1451 +/- 320 g) sedated, spontaneously breathing newborn piglets were studied. VE was measured by pneumotachography, and VO2 was measured by the open-circuit technique. Measurements were performed while the animals breathed room air and repeated after 10 min of hypoxia, which was induced by breathing 10% oxygen. Although the mean VE values during hypoxia displayed a typical biphasic ventilatory response, the individual pattern of this ventilatory response to hypoxia was variable. Thirteen animals sustained VE above baseline after 10 min of hypoxia, whereas the 12 remaining animals decreased VE after 10 min of hypoxia to values below their room air baseline. The VO2 values did not differ between groups during normoxia, and a similar decrease in VO2 occurred in both groups after 10 min of hypoxia. Furthermore, no correlation was observed between changes in VE and VO2 during hypoxia either in absolute values or in the percent change from room air baseline. Arterial PO2 decreased similarly in both groups, but PACO2 decreased significantly only in the group that sustained VE above baseline after 10 min of hypoxia. These data demonstrate that in this animal model the hypoxic ventilatory depression is not determined by the decrease in VO2 that occurs during hypoxia.

Functional residual capacity in normal neonates and children up to 5 years of age determined by a N2 washout method.

Functional residual capacity (FRC) was determined in 50 infants by a simplified N2 washout method. Fourteen infants were preterm, four full-term newborns and the rest were 1 month to 5 yr of age. Weight ranged from 1.19 to 25.8 kg. The method gave well reproducible values with a mean coefficient of variation of 3.9%. The FRC values are equally well correlated to weight and length (r = 0.98). The correlation with weight is linear, intercepting the x axis (FRC = 0) at a weight of 480 g, the one with length is best described by a power curve. The course of the regression lines reflects the observation that FRC per kg weight or per cm length is lower in neonates than in larger infants. The FRC measurements are in the same range as values obtained by other investigators using the N2 washout or He-dilution techniques. The values are significantly smaller than thoracic gas volume measurements obtained by plethysmography. This difference may be due to air trapping or to possible methodological problems with the plethysmographic technique. The data demonstrate that FRC can be measured easily and accurately in preterm and older infants using a N2 washout technique.