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Biomedical subjects

A Jobe

Publications and source records attributed to A Jobe.

At least 55 records · Page 3Linked to original sources
PubMed1987

Corticosteroids and surfactant increase lung volumes and decrease rupture pressures of preterm rabbit lungs.

We measured the effects of corticosteroids and surfactant individually and in combination on lung pressure-volume relationships, rupture pressures, and rupture volumes. Pregnant does were injected with betamethasone (0.1 mg/kg per day im) or vehicle on days 24 and 25 of gestation, and fetal rabbits were delivered on days 26 and 27. Natural surfactant (50 mg/kg body wt) was instilled intratracheally into half of the lungs after tracheotomy. After nine cycles of inflation with air to 40 cmH2O and deflation, air pressure-volume curves were measured. Then the lungs were filled with air to rupture, and rupture volume and pressure were recorded. Both corticosteroids and surfactant caused an increase in maximal lung volumes (P less than 0.01) and a decrease of lung rupture pressures (P less than 0.01) compared with controls. The effects of corticosteroids plus surfactant on lung volumes were the sum of each effect individually, but rupture pressures were the same as those for corticosteroids or surfactant alone. Surfactant, in addition, caused an increase in lung stability at deflation, an effect that was not evident in the corticosteroid-treated groups. Measurements of saturated phosphatidylcholine in alveolar washes and lung tissue indicated comparable values in the corticosteroid and control groups. We conclude that changes in static properties and rupture pressures presumably reflect changes in lung structure caused by corticosteroids that are independent of a corticosteroid effect on surfactant pool sizes.

Animals↗
PubMed1987

Effects of distention of the preterm fetal lamb lung on lung function with ventilation.

Constant distending pressure when applied to the immature fetal lamb lung was reported to improve compliance and prevent the subsequent development of the respiratory distress syndrome after delivery. These experiments were designed to repeat those observations and identify the mechanism(s) responsible for the effects of constant distending pressure on subsequent lung function. The compliance of the lungs of exteriorized fetal lambs at 130 to 133 days gestational age increased 2.5-fold after 1 h of 15 cm of distending pressure. However, subsequent ventilation of the lambs exposed to distending pressure and control lambs resulted in comparable sequential compliance and blood gas and pH measurements. Severity of lung disease as reflected by the peak inspiratory pressure needed to normalize Pco2 values decreased as surfactant-saturated phosphatidylcholine pool sizes increased (r values greater than 0.90) and minimum surface tensions of alveolar washes decreased, but the distention procedure did not change these relationships. Distention of the fetal lung did result in an apparent increase in pulmonary blood flow in the fetus and an increased leak of labeled albumin from the vascular space to the lung interstitium and airways during the 1-h period of ventilation after delivery. However, the leak of protein into the lungs exposed to the distending pressures was not increased during the period of exteriorization and distention, suggesting that distention sensitized the preterm lung to leak protein with subsequent mechanical ventilation. The leak of labeled albumin out of the airways was not changed by distention, and total lung water was not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1987

Corticosteroids and surfactant change lung function and protein leaks in the lungs of ventilated premature rabbits.

Fetal rabbits were treated with corticosteroids by maternal administration for 48 h before delivery at 27 d gestational age. The treated and control rabbits were placed on ventilator-plethysmographs so that ventilation could be adjusted by regulation of tidal volumes to 10-13 ml/kg body wt. [125I]albumin was mixed with fetal lung fluid at birth, alternate rabbits from each litter were treated with Surfactant-TA, and [131I]albumin was injected intravascularly. The movement of the labeled albumins into and out of the alveolar wash and lung tissue was measured after 30 min of ventilation. Corticosteroid treatment (total dose, 0.2 mg/kg betamethasone) significantly decreased the protein leak across the endothelium (P less than 0.001) but increased the protein leak across the epithelium (P less than 0.001). Surfactant treatment decreased both the endothelial and epithelial leaks, and the combination of surfactant and corticosteroid treatments decreased endothelial leaks to 29% of control values and increased compliance more than either treatment alone. The 48-h corticosteroid treatment did not increase alveolar surfactant pool sizes. Corticosteroids significantly changed lung protein leaks independently of surfactant, and improved the response of the preterm lung to surfactant treatments.

Adrenal Cortex Hormones↗
PubMed1987

Comparison of four surfactants: in vitro surface properties and responses of preterm lambs to treatment at birth.

Natural sheep surfactant, rabbit surfactant, human surfactant, and surfactant TA were compared for in vitro surface properties and for responses of preterm lambs to treatment. Equivalent amounts of sheep, rabbit, and human surfactants were needed to lower the surface tension to less than 10 dynes/cm, whereas four times less surfactant TA similarly lowered the surface tension. Surface-spreading rates were similar for the surfactants. The surface adsorption of the batch of human surfactant tested was much slower than was adsorption of the other surfactants. Ventilation was significantly improved in all surfactant-treated lambs relative to the control lambs, indicating the general efficacy of the surfactant treatments. Overall, surfactant TA had the best in vitro characteristics, yet the preterm lambs treated at birth with surfactant TA had lower PO2 values and higher ventilatory requirements than did the sheep surfactant-treated lambs. The in vivo responses to rabbit surfactant were intermediate between the responses to sheep surfactant and to surfactant TA. Human surfactant resulted in the least effective clinical response. More of the phosphatidylcholine associated with human surfactant and surfactant TA was lost from the alveoli and lung tissue after four hours of ventilation than was lost from sheep or rabbit surfactant-treated lambs. More intravascular radiolabeled albumin leaked into the alveoli of the surfactant TA-treated lambs than sheep or rabbit surfactant-treated lambs. The four surfactants also had different sensitivities to the effects on minimum surface tensions of the soluble proteins present in alveolar washes. The study demonstrates that the range of clinical responses was not predictable based on the in vitro surface properties that we measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Respiratory distress and surfactant inhibition following vagotomy in rabbits.

We used the model of bilateral cervical vagotomy of adult rabbits to cause respiratory failure characterized by pulmonary edema, decreased lung compliance, and atelectasis. We documented an 18-fold increase in radiolabeled albumin leak from the vascular space into alveolar washes of vagotomy vs. sham-operated rabbits (P less than 0.01). Despite a twofold increase in percent of prelabeled saturated phosphatidylcholine secreted (P less than 0.01), the alveolar wash saturated phosphatidylcholine pool sizes were not different. The minimum surface tensions were 19.6 +/- 2.5 vs. 9.4 +/- 2.2 dyn/cm for alveolar washes from vagotomy and control rabbits, respectively (P less than 0.01). The soluble proteins from alveolar washes inhibited the surface tension lowering properties of natural surfactant, whereas those from the control rabbits did not (P less than 0.01). When vagotomy rabbits in respiratory failure were treated with 50 mg natural surfactant lipid per kilogram arterial blood gas values and compliances improved relative to control rabbits. Vagotomy results in alveolar pulmonary edema, and surfactant dysfunction despite normal surfactant pool sizes and respiratory failure. A surfactant treatment can improve the respiratory failure.

Animals↗
PubMed1986

Hemodynamic effects of high frequency ventilation in surfactant-treated preterm lambs.

We compared the hemodynamic status and left ventricular (LV) performance in 7 twin pairs of preterm lambs delivered at 124 days gestational age (83% of term gestation) and ventilated by either conventional ventilation (CV) or high frequency ventilation (HFV) at 15 Hz. The lambs were treated with suspensions of natural sheep surfactant to permit ventilation and survival, and ventilatory settings were adjusted to maintain physiologic blood gas values. The ductus arteriosus was occluded with a balloon catheter at 40-45 min of age to eliminate the variable of a left to right ductal shunt. Cineangiocardiographic, pressure, and blood flow measurements were made 1 and 2 h after ductal occlusion. At the same mean airway pressures, the heart rates, LV end-diastolic volumes, and mean arterial pressures were similar in both groups. LV stroke volumes, ejection fractions, LV outputs, and organ blood flows also did not differ between the two groups. When compared with CV, HFV provides comparable ventilation with no apparent deleterious hemodynamic effects in preterm surfactant-treated lambs with occluded ductus arteriosus.

Acid-Base Equilibrium↗
PubMed1986

A protein that inhibits surfactant in respiratory distress syndrome.

A protein that interferes with surfactant function is present in the airways and alveoli of infants with respiratory distress syndrome (RDS). This inhibitor is also found in serum and amniotic fluid and presumably appears in the alveoli because of the abnormal protein leak present in the lungs of infants with RDS. This protein has a molecular weight of about 110,000 and is resistant to boiling or lipid extraction. As measured by radioimmunoassay, the ratio of inhibitor to phosphatidylcholine decreased from 8.1 +/- 2.3 early in the course of RDS to 0.7 +/- 0.1 on the day of extubation. The value at extubation was the same as that measured for preterm infants without RDS. The inhibitor to phosphatidylcholine ratio in airway samples from infants with RDS correlated significantly with simultaneously recorded pO2/FiO2 ratios and the peak inspiratory pressures used to normalized pCO2 values. These results are consistent with the concept that the inhibitor contributes to surfactant dysfunction and thus the respiratory failure characteristic of RDS.

Amniotic Fluid↗
PubMed1986

Left ventricular performance and contractility before and after volume infusion: a comparative study of preterm and full-term newborn lambs.

We studied left ventricular performance and contractility after volume loading in lambs at 122 days (group I, n = 9) and 139 days gestational age (group II, n = 9) and in 8-day-old full-term lambs (group III, n = 7). All were mechanically ventilated; each preterm lamb was treated with surfactant to stabilize pulmonary function and the ductus arteriosus was occluded with an inflated catheter balloon. Cineangiograms, left ventricular and vascular pressures, and the isovolumetric index of contractility, first derivative of left ventricular pressure (dP/dt), were recorded before and after three successive whole blood volume infusions of 10 ml/kg (total 30 ml/kg). The left ventricular end-diastolic volume per kilogram and stroke volume per kilogram increased significantly in all groups after volume infusion; these measurements and heart rate and systemic vascular resistance did not differ significantly between the groups either before or after the infusions. The left ventricular peak dP/dt did not change significantly within the groups during the volume infusions. The left ventricular stroke work was greatest in full-term animals and increased significantly in all groups after volume infusion. Thus, the left ventricles of the preterm and full-term lambs had quantitatively similar Frank-Starling responses and there was no increase in contractility during the infusions of whole blood. However, the left ventricle of the full-term lamb is capable of generating greater stroke work than that of the preterm lamb. These findings may contribute to the understanding of development aspects of postnatal circulatory adaptation.

Animals↗
PubMed1986

Clearance of natural surfactant phosphatidylcholine from 3-day-old rabbit lungs: effects of dose and species.

Surfactants were labeled in vivo with [3H] choline and the large aggregates of the surfactant were recovered by alveolar wash and centrifugation. The labeled natural surfactants from rabbit, sheep, cat, and pig were injected into the airways of 3-day-old rabbits, and the percent recoveries of the labeled surfactant-associated phosphatidylcholine were measured in alveolar washes, lung tissue after alveolar wash, and in the lungs (alveolar wash plus lung tissue). The rabbit surfactant-associated phosphatidylcholine was cleared from the lungs at a constant 15.6 +/- 1.8% per 24 h (mean +/- SE) of the injected doses of surfactant that contained from 0.41 to 10.2 mumol phosphatidylcholine. At all times following injection, approximately 50% of the labeled phosphatidylcholine remaining within the lungs was recovered in the alveolar wash and 50% with the lung tissue. The percent clearances for sheep, cat, and pig surfactant phosphatidylcholine in rabbits were 12.5, 16.6, and 16.3% per 24 h, respectively, values not different from that measured for rabbit surfactant. The results documented a slow clearance of exogenously administered surfactant phosphatidylcholine as a fixed percent of the injected dose that was unchanged by species source of the surfactant.

Animals↗
PubMed1985

Liposomes of dipalmitoylphosphatidylcholine associate with natural surfactant.

Unilamellar liposomes of an average diameter of 0.05 micron formed by sonication of dipalmitoylphosphatidylcholine associate in vitro with the large aggregate forms of natural surfactant. The liposomal-surfactant aggregates are stable and previously associated liposomes are not released from the aggregates by the addition of more liposomes. Radiolabeled liposomes, surfactant, and preformed liposomal-surfactant aggregates were injected at a dose of 8-10 mg lipid (about 2-times the endogenous surfactant pool size) into the airways of 3-day-old rabbits. Following airway injection, labeled phosphatidylcholine from the liposomal-surfactant aggregates were recovered in approximately equal amounts by alveolar wash and in the residual lung tissue fractions. This recovery pattern and the clearance kinetics were equivalent for 48 h after airway injection to those measured with radiolabeled surfactant alone. In contrast, following the injection of liposomes alone, labeled phosphatidylcholine from the liposomes was recovered primarily by alveolar wash at 3 and 24 h. The overall clearance of the liposomal-derived phosphatidylcholine from the lung was more rapid than was the clearance of the phosphatidylcholine from the surfactant or liposome-surfactant complexes. Liposomes can interact with surfactant in vitro, and the liposomes associated with the surfactant aggregate have a metabolic fate in vivo similar to surfactant and different from liposomes alone.

Animals↗
PubMed1985

Leakage of protein in the immature rabbit lung; effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.

Albumins↗
PubMed1985

Lung protein leaks in ventilated lambs: effects of gestational age.

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.

Albumins↗
PubMed1985

Effects of high-frequency and conventional ventilation on the premature lamb lung.

Twelve sets of twin lambs were delivered prematurely by cesarean section at 133-136 days gestational age and ventilated for 3 h with either high-frequency oscillation (HFO) or conventional mechanical ventilation (CMV). Blood gases and pH values were monitored at 30-min intervals, and ventilator settings were adjusted to maintain CO2 partial pressure (PCO2) values within the normal range. There were no differences in the sequential blood gas or pH values between the HFO or CMV lambs. Mean airway pressures (MAP) between 8.0 and 20.4 cmH2O were required, indicating lung disease of variable severity in the lambs. The bidirectional protein leak from the vascular space to the airways and alveoli and vice versa was measured with radiolabeled albumins given by intravascular injection and with fetal lung fluid at birth. The albumin leaks in both directions increased as MAP required to normalize PCO2 increased, but the degree of leak was independent of type of ventilation. Pathological findings of epithelial necrosis and hyaline membranes occurred to a similar extent in lung sections from both groups of lambs. In the HFO animals less phosphatidylcholine in the alveolar wash and more of a tracer dose of radiolabeled natural surfactant that had been given at birth became tissue associated. These results indicate a decrease in the initial secretion of surfactant and/or a stimulation of reuptake in the HFO animals. HFO did not protect the immature lung from the development of large protein leaks or the pathological changes of the respiratory distress syndrome.

Animals↗
PubMed1985

Distribution of pulmonary blood flow in relation to atelectasis in premature ventilated lambs.

To investigate the ability of the preterm, ventilated lung to redirect blood flow away from atelectatic regions, we studied lambs with respiratory distress syndrome and spontaneous atelectasis or atelectasis caused by bronchial obstruction with a balloon catheter. Pulmonary blood flow distributions were measured by quantifying 15-mu, microsphere-associated radioactivity within multiple pieces of lung. Lambs with well aerated or very atelectatic lungs had relatively uniform blood flow/gram lung in all pieces of lung. Blood flow was much less uniform in lungs with both aerated and atelectatic regions. In 9 lambs with spontaneous atelectasis that included 25 +/- 5% (mean +/- SE) of the lungs by weight, blood flow was 29 +/- 4% less to atelectatic than to aerated lung volumes (p less than 0.01). In 5 lambs with well-aerated lungs, 18 +/- 3% of the lung by weight was made atelectatic by balloon occlusion of a major lower lobe bronchus. There was a 44 +/- 11% decrease in blood flow to the atelectatic lung segments. These studies document the ability of the lung of the premature, ventilated lamb to shunt pulmonary blood flow away from atelectatic lung volumes.

Animals↗
PubMed1985

The contractility and performance of the preterm left ventricle before and after early patent ductus arteriosus occlusion in surfactant-treated lambs.

The influence of left-right ductal shunting on early hemodynamic responses, namely left ventricular performance, contractility, and systemic perfusion was evaluated in nine preterm lambs (120 days gestational age) treated with surfactant. Blood gases were maintained in the physiological range using mechanical ventilation; hemodynamic and blood flow measurements (radionuclide labeled microspheres) were obtained before and after occlusion of the patent ductus arteriosus with a catheter balloon. The mean left-right ductal shunt before occlusion (1.2 h postnatal age) was 59 +/- 11% SD. Left ventricular output was increased in all lambs with PDA (pre: 306 +/- 106 versus post: 155 +/- 31 ml/min/kg; p less than 0.001); effective systemic blood flow and organ blood flows did not change. The left ventricle end-diastolic volume was increased in all and decreased following ductal occlusion (pre: 2.0 +/- 0.4 versus post: 1.5 +/- 0.2 ml/kg; p less than 0.01). Cardiac rate, ejection fraction, and contractility (peak dP/dt) did not change. Right-left ductal shunting was not detected in six similarly treated lambs. Thus, during the 1st h of life the hemodynamic profile of preterm lambs with patent ductus arteriosus was characterized by large magnitude left-right shunt and a "high" cardiac output state sufficient to maintain unchanged systemic perfusion. The increased left ventricle output was accomplished by increasing end-diastolic volume (Frank-Starling mechanism), but left ventricle contractility remained unchanged. We speculate that the preterm left ventricle may be unable to sustain the high level of pump performance and contractility required to compensate for the ductal "steal" of systemic blood flow.

Animals↗