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Biomedical subjects

T A Standaert

Publications and source records attributed to T A Standaert.

At least 73 records · Page 4Linked to original sources

Postnatal changes in transdiaphragmatic pressure in piglets.

We examined diaphragmatic force output in 25 anesthetized piglets ranging in postnatal age from 4 to 21 days (weight 1.3-4.0 kg) in order to determine whether the diaphragm produces greater force output with maturation for a given level of neural input. Transdiaphragmatic pressure (Pdi) served as our index of diaphragmatic force output and was measured during "supramaximal" transvenous phrenic nerve stimulation at 100 Hz in order to control neural drive. Mean Pdi was 53 +/- 17 cm H2O and ranged from a minimum of 29 cm H2O to a maximum of 83 cm H2O. A significant positive correlation between Pdi and postnatal age was observed (r = 0.79, p less than 0.001). In addition, positive correlations were noted between Pdi and total body weight (r = 0.73, p less than 0.001) and Pdi and diaphragmatic wet weight (r = 0.77, p less than 0.001). The voltage needed to stimulate the phrenic nerves "supramaximally" did not correlate with postnatal age (r = 0.02, p = 0.16). We conclude that a developmental pattern of increasing Pdi with increasing postnatal age, total body weight, and diaphragmatic wet weight exists in piglets and occurs within the context of a controlled level of neural drive.

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Surfactant quantity and composition during recovery from hyaline membrane disease.

The appearance of phosphatidylglycerol in the tracheal wash of infants with hyaline membrane disease (HMD) has been reported to be associated with clinical signs of recovery. We analyzed lung tissue and bronchoalveolar lavage surfactant in an animal model of HMD to determine whether phosphatidylglycerol or some other component is necessary for recovery. The amount and composition of phospholipid (PL) was determined in the premature Macaca nemestrina monkey (140 days' gestation) during an acute stage of HMD, and in two stages of recovery. These changes were compared to observations made in healthy premature controls (140 days), gestational age-matched fetuses (140 days), and fetuses of 150 days' gestation (term = 168 days). The amount of PL and its surfactant composition in lung homogenates of the right lower lobe and in lavage of the excised left lung was determined. Compared to 140-day fetuses, the healthy controls had a several-fold increase in lavage PL and disaturated phosphatidylcholine (DSPC) during the first few days of life (p less than 0.05). Prior to recovery, animals with HMD had no such increase in lavage PL or DSPC and demonstrated poor deflation stability. Recovery was associated with increased tissue and lavage PL (p less than 0.05) and increased fractions of phosphatidylinositol and DSPC (p less than 0.05), but not phosphatidylglycerol. The tissue compositional changes observed during recovery reflected maturational changes observed in the fetal animals studied at 10 days' greater gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

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The matching of ventilation and perfusion in the lung of the Tegu lizard, Tupinambis nigropunctatus.

Ventilation-perfusion (VA/Q) distribution was evaluated in the Tegu lizard, Tupinambis nigropunctatus, using the multiple inert gas elimination technique (MIGET) in order to define the limitations to gas exchange in the large chambered unicameral lung. The lizards (0.52-1.1 kg) were anesthetized with halothane and ventilated. Body temperature was maintained at 35 degrees C. Arterial and sinus venosus PO2 averaged 79.4 +/- 5.9 and 47.3 +/- 6.4 torr while breathing air and 232.1 +/- 31 and 64.8 +/- 11.5 torr while breathing oxygen. VA/Q distributions were broad and right-to-left shunt averaged 21% while breathing air and 27% while breathing oxygen. Gas exchange was significantly impaired due to the presence of both shunt and VA/Q heterogeneity. The walls of the lung enclose a large axial air chamber. Microscopic examination revealed approximately three generations of septa which subdivided the wall into tubular-shaped gas-exchange chambers. Wall thickness averages 2.8 mm at the anterior end of the lung, 2.1 mm in the middle portion of the lung and 1.4 mm at the posterior end. The thickness of the blood-air barrier (epithelial-basal lamina-endothelial cell layer) ranged from 0.35 to 0.90 micron. Although this barrier is slightly thicker than in the mammalian lung (0.1-0.5 micron), it is unlikely to be a source of diffusion limitation in gas exchange at rest.

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Serial determination of lung volume in small animals by nitrogen washout.

This report describes the design of an apparatus and the procedures used to serially measure the total lung capacity and the functional residual capacity of small animals utilizing the N2-washout technique. The calibration data indicate that the technique is accurate to within 1 ml and has a variance of less than 5%. The in vivo lung volume measurements of rats were validated by comparing them with values obtained with a water-displacement technique; the means were within 0.3 ml. Examples of the precision and changes in lung volume of animals during studies are included to demonstrate the reliability and usefulness of the technique.

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Effect of high-frequency ventilation on gas exchange and pulmonary vascular resistance in lambs.

We studied the effects of conventional mechanical ventilation (CMV) (15 ml/kg tidal volume delivered at 18-25 breaths/min) and high-frequency oscillatory ventilation (HFOV) (less than or equal to 2 ml/kg delivered at 10 Hz) on pulmonary hemodynamics and gas exchange during ambient air breathing and hypoxic gas breathing in 10 4-day-old lambs. After instrumentation and randomization to either HFOV or CMV the animals breathed first ambient air and then hypoxic gas (inspired O2 fraction = 0.13) for 20 min. The mode of ventilation was then changed, and the normoxic and hypoxic gas challenges were repeated. The multiple inert gas elimination technique was utilized to assess gas exchange. There was a significant increase with HFOV in mean pulmonary arterial pressure (Ppa) (20.1 +/- 4.2 vs. 22 +/- 3.8 Torr, CMV vs. HFOV, P less than 0.05) during ambient air breathing. During hypoxic gas breathing Ppa was also greater with HFOV than with CMV (29.5 +/- 5.7 vs. 34 +/- 3.1 Torr, CMV vs. HFOV, P less than 0.05). HFOV reduced pulmonary blood flow (Qp) during ambient air breathing (0.33 +/- 0.11 vs. 0.28 +/- 0.09 l . kg-1 . min-1, CMV vs. HFOV, P less than 0.05) and during hypoxic gas breathing (0.38 +/- 0.11 vs. 0.29 +/- 0.09 l . kg-1 . min-1, P less than 0.05). There was no significant difference in calculated venous admixture for sulfur hexafluoride or in the index of low ventilation-perfusion lung regions with HFOV compared with CMV.(ABSTRACT TRUNCATED AT 250 WORDS)

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Changes in lung volume and deflation stability in hyaline membrane disease.

Total lung capacity (TLC), inspiratory capacity, functional residual capacity, and deflation stability of prematurely delivered Macaca nemestrina primates were measured serially during development of, and recovery from, hyaline membrane disease (HMD) to relate changes in lung volumes to changes in deflation stability. Gestational age-matched primates that did not develop HMD served as controls. TLC, measured by N2 washout, fell at 2-12 h of age (P less than 0.0001) in animals with HMD and remained lower than controls for at least 48 h (P less than 0.005). However, deflation stability, defined as the fraction of TLC remaining upon deflation to 10 cm H2O, improved from 2 to 12 h of age (P less than 0.001). Postmortem studies confirm the measurements of TLC and deflation stability and provide evidence that interstitial thickening and obstruction of air spaces with debris may be partially responsible for the observed changes in TLC in primates that develop HMD. It has been assumed that TLC is reduced in HMD because of atelectasis from elevated alveolar surface tension, but the sequential measurements in these animals suggest that other mechanisms also contribute.

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Ventilatory interaction between oxygen and carbon dioxide in the preterm primate.

The steady state ventilatory response to inhaled CO2 was measured in eleven unanesthetized premature Macaca nemestrina during the first 3 wk of life in different steady state background O2 mixtures hypoxia (FIO2 = 0.08 or 0.12), normoxia (FIO2 = 0.21) and hyperoxia (FIO2 = 0.96). Hyperoxic delta VI/delta PACO2 and delta P0.2/ delta PACO2 were significantly greater than hypoxic delta VI/ delta PACO2 and delta P0.2/delta PACO2, respectively, at both 2 and 21 days postnatal age by the Mann Whitney test of nonparametric ranking (2 days: 89.. and 80.2 degrees versus 88.7 and 56.4 degrees, respectively; 21 days: 89.3 and 76.6 degrees versus 50.2 and 57.1 degrees, respectively; p less than 0.05). Hypoxic delta VI/delta PACO2 was significantly depressed compared to normoxic delta VI/ delta PACO2 only at 21 days of age (50.2 versus 89.4 degrees, respectively; p less than 0.05); hyperoxic CO2 sensitivity and normoxic CO2 sensitivity did not differ at either age. The ventilatory interaction between O2-CO2 in the neonatal primate appears to be the inverse of the typical adult ventilatory interaction. It is hypothesized that differential changes in brain stem blood flow between neonates and adults might explain this difference in O2-CO2 ventilatory interaction.

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Alterations in gas exchange associated with lobar atelectasis in young piglets.

Lobar atelectasis is common among infants and children with obstructive lung diseases. However, the effect of lobar collapse in the presence of diffuse lung disease on gas exchange in the pediatric age group has not been described. We developed an infant model of lobar atelectasis using piglets and tested the hypothesis that diffuse alveolar hypoxia increases shunt fraction (Qs/QT) associated with lobar atelectasis by redirecting pulmonary blood from the well-ventilated portion of the lung into the collapsed region. Shunt fraction was determined using the multiple inert gas elimination technique. The proportion of pulmonary blood flow perfusing the left lower lobe was measured with microspheres. Qs/QT increased significantly but by a variable amount to an average value (+/- SD) of 5.9 +/- 4.2% following lobar collapse. The percentage of cardiac output perfusing the left lower lobe fell by an average of 70 +/- 17% in response to lobar collapse. When animals were ventilated with 12% oxygen, shunt fraction increased to 18.7 +/- 7.1% and blood flow to the collapsed left lower lobe increased from 9 +/- 3 to 22 +/- 3% of cardiac output. Lobar atelectasis in conditions where diffuse alveolar hypoxia is present may be associated with a significantly greater intrapulmonary shunt than lobar atelectasis in children with otherwise normal lungs.

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Effect of dopamine infusion on pulmonary gas exchange in lambs.

We studied the effects of dopamine HCl, a potent vasoactive catecholamine, on ventilation-perfusion matching and pulmonary hemodynamics in infant lambs breathing room air and a hypoxic gas mixture. Neither alveolar hypoxia alone, nor dopamine infusion alone during room air breathing, significantly altered the ventilation-perfusion (VA/Q) distribution or intrapulmonary shunt size. Dopamine infusion during room air breathing did increase pulmonary blood flow (PBF; p less than 0.05). Dopamine infusion plus alveolar hypoxia was associated with a significant increase in minute ventilation, PBF, and pulmonary arterial pressure (Ppa), a doubling (p less than 0.01) of the fraction of PBF to low VA/Q lung regions, and a significant increase (p less than 0.05) in intrapulmonary shunt when compared to results obtained during hypoxic gas breathing without dopamine infusion. We conclude the dopamine infusion increased PBF during room air breathing, and perturbed ventilation-perfusion matching and increased Ppa and minute ventilation with no net change in arterial pO2 during the breathing of a hypoxic gas mixture.

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Effects of prolonged high-frequency oscillatory ventilation in premature primates with experimental hyaline membrane disease.

The effects of 24 h of high-frequency oscillatory ventilation (HFOV) applied to premature primates with hyaline membrane disease (HMD) were assessed by serial gas exchange and in vivo lung distensibility measurements, and by postmortem lung phospholipid analysis. Results in 7 animals with HMD treated with HFOV were compared with those in 6 animals with HMD treated with conventional mechanical ventilation. No differences in arterial to inspired PO2 ratios, total lung capacity, airway lavage, or lung homogenate phospholipid or disaturated phosphatidylcholine were found between the 2 groups. Arterial PCO2 was lower in the HMD-HFOV group at 6 and at 12 h. There was no difference in lung dry to wet weight ratios; the ratio in both groups of HMD animals was less than that for premature primates without HMD. We conclude that HFOV is useful in maintaining adequate CO2 elimination but does not improve arterial oxygenation or alter the natural history of experimental HMD.

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An elastic loading system for ventilatory studies in small animals.

A system for studying the effects of prolonged inspiratory elastic loading in small animals (300-500 g) is described. A voltage comparator triggered by the expired flow signal activates a solenoid valve to vent the loading chamber after each inspiratory decompression, ensuring the presentation of a constant extrapulmonary elastance. The sensitivity of the comparator (5 mV) and the response time of the venting circuit (40 ms) make this system suitable for use in small subjects with tidal volumes less than 1 ml and respiratory frequencies exceeding 100 breaths . min-1. Additionally, the composition of the inspiratory gas is easily altered and a built-in device allows end-expiratory occlusions to be performed.

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Dopamine and carotid body function in the newborn lamb.

The effect of dopamine on the acute ventilatory response to hypoxia was investigated in four newborn lambs studied on the 1st day of postnatal life and eight lambs studied between 7 and 12 days of age. Studies were accomplished during nonrapid-eye-movement sleep in unanesthetized tracheotomized animals. Changes in minute ventilation (VE/kg), tidal volume, and frequency induced by intravenous bolus injection of dopamine (10 micrograms/kg) or saline control were assessed while animals were breathing room air or N2, before and after carotid body denervation (CBD). Dopamine depressed resting ventilation at both postnatal ages. This effect was greater in the older animals. Dopamine blunted the hypoxia-induced increase in VE/kg at both ages. The magnitude of this depression did not vary with postnatal age. Dopamine induced cessation of respiratory effort at end expiration (apnea) during room air and N2 breathing significantly more often in the older animals. The effect of dopamine was mediated at the carotid body. CBD decreased ventilation by an increase in breath-to-breath interval in older animals, suggesting carotid sinus nerve afferent activity is more important during eucapnic respiration in older animals than in the immediate newborn period.

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Pulmonary mechanics during the ventilatory response to hypoxemia in the newborn monkey.

Dynamic lung compliance (CL), inspiratory pulmonary resistance (RL), and functional residual capacity (FRC) were measured in 10 unanesthetized 48 h-old newborn monkeys and seven 21-day-old infant monkeys during acute exposures to an equivalent level of hypoxemia. End-expiratory airway occlusions were performed and the pressure developed by 200 ms (P0.2) was utilized as an index of central respiratory drive. P0.2 demonstrated a sustained increase throughout the period of hypoxemia on day 2 despite the fact that minute ventilation (VI) initially increased but then fell back to base-line levels. Dynamic lung compliance fell and FRC increased by 5 min of hypoxemia in the newborns. The 21-day-old monkeys exhibited a sustained increase in both VI and P0.2 throughout the hypoxic period with no change in CL and FRC. RL did not change at either postnatal age during hypoxemia. These data indicate that the neonatal monkey is subject to changes in pulmonary mechanics (decreased CL and increased FRC) during hypoxemia and that these changes are eliminated with maturation.

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Antenatal glucocorticoid administration: effects on oxygen-hemoglobin affinity and hemoglobin levels in experimental hyaline membrane disease.

Dexamethasone or saline was administered in a randomized fashion to pregnant Macaca nemestrina for 3 days prior to preterm abdominal delivery. The steroid-treated animals demonstrated a greater hemoglobin concentration and a greater mean corpuscular hemoglobin concentration in cord blood. There was no difference between the groups in mean P50 in cord blood. The infants of steroid-treated animals had less frequent and less severe hyaline membrane disease. We conclude that antenatal steroid administration ameliorates postnatal respiratory distress without inducing changes in P50 and with only a small change induced in cord blood hemoglobin.

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Effect of high-frequency oscillation on gas exchange and pulmonary phospholipids in experimental hyaline membrane disease.

Arterial PO2 and PCO2 obtained with 2 modes of mechanical ventilation were compared in 5 premature monkeys with hyaline membrane disease (HMD) during the first 7 h of life. High-frequency oscillation (HFO) (10 Hertz) was compared with conventional positive-pressure ventilation (CMV) by matching the mean airway pressure generated by the 2 systems. Each animal served as its own control; HFO sustained an improved PaCO2 (39 +/- 8 versus 25 +/- 7 mmHg). An insignificant improvement in arterial PO2 was noted. The improved CO2 exchange occurred with a lower peak airway pressure (35 +/- 4 versus 23 +/- 11 cm H2O). Comparison of the postmortem pressure-volume curves and lung and lavage phospholipid concentrations from the animals treated with HFO in the current study to a matched set of animals treated exclusively with CMV in a previous study failed to reveal any differences. We conclude that HFO is effective in eliminating CO2 in experimental HMD without apparently altering lung biochemical or mechanical properties in a manner different from that found with CMV.

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Effects of PEEP and tolazoline infusion on respiratory and inert gas exchange in experimental meconium aspiration.

Meconium aspiration syndrome often produces respiratory failure in the neonate. We utilized the multiple inert gas elimination technique to study the effects on respiratory and inert gas exchange of the application of positive end expiratory pressure or continuous infusion of tolazoline HCl. The application of PEEP, with the optimal level of PEEP defined for each animal, produced a decrease in AaDO2 and pulmonary shunt, without an increase in blood flow to low VA/Q areas, or an increase in dead space. Tolazoline infusion, at 2 mg/kg/hour, had no apparent effect on AaDO2 or shunt, or magnitude of low VA/Q regions. Tolazoline therapy was associated with an increase in heart rate and a decrease in systemic blood pressure. We conclude that immediate postaspiration application of PEEP, but not of tolazoline, will diminish pulmonary shunt without creating low VA/Q areas, and therefore will improve gas exchange in MAS.

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Respiratory and inert gas exchange during high-frequency ventilation.

Pulmonary gas exchange during high-frequency low-tidal volume ventilation (HFV) (10 Hz, 4.8 ml/kg) was compared with conventional ventilation (CV) and an identical inspired fresh gas flow in pentobarbital-anesthetized dogs. Comparing respiratory and infused inert gas exchange (Wagner et al., J. Appl. Physiol. 36: 585--599, 1974) during HFV and CV, the efficiency of oxygenation was not different, but the Bohr physiological dead space ratio was greater on HFV (61.5 +/- 2.2% vs. 50.6 +/- 1.4%). However, the elimination of the most soluble inert gas (acetone) was markedly enhanced by HFV. The increased elimination of the soluble infused inert gases during HFV compared with CV may be related to the extensive intraregional gas mixing that allows the conducting airways to serve as a capacitance for the soluble inert gases. Comparing as exchange during HFV with three different density carrier gases (He, N2, and Ar), the efficiency of elimination of Co2 or the intravenously infused inert gases was greatest with He-O2. However, the alveolar-arterial partial pressure difference for O2 on He-O2 exceeded that on N2-O2 by 5.4 Torr during HFV. The finding agrees with similar observations during CV, suggesting that this aspect of gas exchange is not substantially altered by HFV.

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Experimental hyaline membrane disease in the premature monkey: effects of antenatal dexamethasone.

A blind, randomized trial of antenatal glucocorticoid treatment was conducted using the premature monkey (Macaca nemestrina) model of hyaline membrane disease (HMD). Twelve dams received dexamethasone (2 mg/dose) 72, 48, and 24 h before abdominal delivery at 135 +/- 1 days of gestation. Twelve control animals received saline. Infants of dexamethasone-treated dams had significantly lower incidence and severity of HMD than did infants of control animals (50 versus 92%, p less than 0.05). Improvement with treatment was markedly greater for males than for females. Differences in volume-pressure behavior of the excised lungs included greater distensibility in the infants from dexamethasone-treated dams (20.6 +/- 7.1 ml/g dry lung versus 14.7 +/- 6.1, p less than 0.05) and enhanced deflation stability with treatment. Accelerated production of surface active material (SAM) phospholipids in infants from dexamethasone-treated dams was indicated by increases in total lung phospholipid (84.5 +/- 8.1 mg/g dry lung versus 75.1 +/- 9.9, p less than 0.025), alveolar lavage fluid phospholipid (5.65 +/- 3.33 mg/g dry lung versus 3.01 +/- 1.84, p less than 0.05), and alveolar lavage fluid disaturated phosphatidylcholine (DPC) (2.47 +/- 1.84 mg/g dry lung versus 1.06 +/- 1.05, p less than 0.05). Incorporation of 14C-palmitate into lung lipid was not influenced by dexamethasone, but a significantly greater portion of the label appeared in the DPC fraction with treatment. Antenatal dexamethasone treatment was successful in reducing the incidence and severity of experimental HMD in this animal model; the beneficial effects of treatment were associated with accelerated maturation of fetal pulmonary functions, including, but not limited to, synthetic metabolism of SAM phospholipid.

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