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A H Jobe

Publications and source records attributed to A H Jobe.

At least 127 records · Page 7Linked to original sources
PubMed1994

In vivo function of surfactants containing phosphatidylcholine analogs.

Increased phospholipase A2 activity demonstrated in some forms of lung injury may contribute to surfactant dysfunction. Phospholipase A2-resistant analogs of dipalmitoylphosphatidylcholine (DPPC) with surfactant properties might therefore be useful lipid components of treatment surfactants for certain lung injuries. The in vivo function of surfactants containing DPPC or the phospholipase-resistant analogs dihexadecylphosphatidylcholine (DEPC) or dihexadecylphosphonotidylcholine (DEPnC), with or without surfactant proteins B and C (SP-B+C), was thus evaluated in preterm rabbits (27 days' gestation). Rabbits randomly received one of seven surfactants (DPPC, DEPC, DEPnC, DPPC+SP-B+C, DEPC+SP-B+C, DEPnC+SP-B+C, or lipid extract surfactant [LES]) or 0.45% NaCl (control) and were ventilated for 30 min. Lipid-only surfactants decreased ventilatory pressures (peak inspiratory pressures minus positive end-expiratory pressure) relative to control (p < 0.05). Addition of SP-B+C further decreased ventilatory pressures to levels similar to LES (p < 0.01 versus control, lipid-only surfactants). Lung dynamic compliances and postventilation pressure-volume curves improved in the following order: LES, SP-B+C lipid surfactants > lipid-only surfactants > control (p < 0.05). All surfactant preparations decreased intravascular 125I-albumin recoveries in the lungs relative to control (p < 0.01 for all surfactants versus control). These results indicate that DEPC and DEPnC were as effective as DPPC as lipid components of synthetic surfactants. And like DPPC, the analogs interacted with isolated SP-B+C and improved in vivo function to levels comparable to LES.

Animals↗
PubMed1994

Changes in alveolar surface area, surfactant protein A, and saturated phosphatidylcholine with postnatal rat lung growth.

Most previous studies of the relationship between surfactant and growth have correlated surfactant pool size with lung weight or body weight. We asked how the quantities of the surfactant components surfactant protein A (SP-A) and saturated phosphatidylcholine (Sat PC) recovered by alveolar wash changed with age in relationship to morphologic measurements of alveolar surface area in rats. We also calculated SP-A and Sat PC in total lung per surface area. In groups of three to 14 rats studied on d 1, 7, 14, 21, 50, and 100 of age, the ratio of alveolar surface area to body weight was highest at d 14 and lowest at d 100. Alveolar and total lung SP-A and Sat PC were higher relative to body weight and surface area on d 1 than at all other ages. Alveolar and total lung SP-A peaked relative to surface area at d 21 and subsequently decreased significantly at d 100. The alveolar Sat PC to surface area ratio also was highest at d 21 and decreased significantly at d 50 and 100. The SP-A to Sat PC ratio in alveolar washes was not constant across this age range, being highest at d 21 and 50. These measurements demonstrate age-dependent changes in alveolar and total lung SP-A and Sat PC in the rat that continue beyond the newborn period.

Age Factors↗
PubMed1994

Corticosteroids and fetal intervention interact to alter lung maturation in preterm lambs.

The relationship between cortisol infusion and time of fetal catheterization on postnatal lung function of prematurely delivered lambs was investigated with the hypothesis that the intervention of catheterization would alter fetal responsiveness to the maturational effects of corticosteroids. Fetal catheterization was performed on d 117 or on d 122 of gestation. Cortisol or saline control infusions were begun on d 126, with delivery 60 h later on d 128. The animals were ventilated for 1.25 h after delivery, and compliance, the ventilation efficiency index, labeled albumin leak into and out of the lungs, alveolar and lung saturated phosphatidylcholine and surfactant protein A were measured to evaluate lung performance and biochemical indicators of maturation. Cortisol improved compliance and ventilation efficiency and decreased labeled albumin recovery without changing alveolar saturated phosphatidylcholine or surfactant protein A in the animals catheterized at 122 d relative to 122-d saline-infused animals. However, the animals catheterized at 117 d and infused with saline were as mature as assessed by compliance and ventilation efficiency as the 122-d cortisol-treated animals. The 117-d cortisol-infused animals had significantly augmented lung function relative to either 117-d saline-infused or 122-d cortisol-treated lambs and were the only group that had increased alveolar surfactant protein A and lung saturated phosphatidylcholine pool sizes. This study demonstrates that the response of the fetal lung to a maturational agent such as cortisol is dependent on the history of previous fetal interventions.

Albumins↗
PubMed1993

Beneficial effects of the combined use of prenatal corticosteroids and postnatal surfactant on preterm infants.

OBJECTIVE: Our objective was to test the hypothesis that prenatal maternal corticosteroids would improve the subsequent response of infants to surfactant treatments. STUDY DESIGN: We used the data bases of two recently published large multicenter trials of multidose surfactant treatments to retrospectively evaluate the possible interactions between maternal corticosteroids and randomized surfactant treatments on short-term ventilatory effects, complications of respiratory distress syndrome and prematurity, and 28-day death rates. RESULTS: The combined use of corticosteroids and surfactant significantly decreased overall death and death caused by respiratory distress syndrome relative to either treatment alone. Ventilatory variables at 72 hours were improved in those infants receiving both treatments, and other major complications of prematurity also tended to have decreased incidences. CONCLUSION: The combined use of prenatal corticosteroids, when indicated, and postnatal surfactant improves neonatal outcome.

Adrenal Cortex Hormones↗
PubMed1993

Surfactant treatment effects on alveolar type II cell morphology in rabbit lungs.

The effects of exogenous surfactant administration on alveolar type II cells and the lung parenchyma were examined in adult rabbits. Natural surfactant was instilled into the left lobe of New Zealand White rabbits while the right lobe served as the control. Four hours post-instillation, the lungs were fixed by vascular perfusion. Surfactant instillation did not change alveolar type II cell size but was associated with a significant reduction in the volume fraction of lamellar bodies in type II cells (20.4% in control lobes compared with 11.9% in surfactant-treated lobes). The size distribution of lamellar body profiles was different in surfactant-treated lobes compared with control lobes, with a significant decrease in lamellar bodies > 0.8 microns in diameter and a twofold increase in lamellar bodies 0.2-0.4 microns in diameter. Composite body profile number was also increased by 87% (P < 0.05) after instillation of surfactant compared with control. Saline instillation decreased lamellar body volume fraction in type II cells but three times less than surfactant instillation. These observations are consistent with a strong stimulus for secretion of endogenous surfactant 4 h after surfactant instillation in normal adult rabbit lungs, whereas the increase in composite bodies is consistent with new lamellar body formation, probably from both de novo synthesized and exogenous natural rabbit surfactant. These observations confirm that the secretory and synthetic processes of alveolar type II cells are significantly affected by exogenous surfactant instillation.

Animals↗
PubMed1993

Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant.

Adult sheep (35 +/- 3 kg) underwent saline lung lavage and 1.5 h of mechanical ventilation to induce acute lung injury. Animals received 100 mg lipid/kg body wt of tracheally instilled surfactant (Inst Surf) or either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) and were killed 3 h later. Inst Surf and Neb Surf groups had significant improvements in oxygenation (P < 0.01) and peak inspiratory pressures (PIP) (P < 0.05) compared with pretreatment values. Improvements in oxygenation and PIP for Inst Surf animals were significantly greater than for Neb Surf animals (P < 0.05). Volumes of maximal pressure of quasi-static pressure-volume curves measured at the time the animals were killed were significantly greater for Inst Surf and Neb Surf animals than for animals given Neb Saline (P < 0.05). Alveolar recovery of exogenous surfactant was 100 times greater for Inst Surf animals (1,732 +/- 70 mg) than for Neb Surf animals (15.3 +/- 2.9 mg) at the time they were killed. Although there were no differences in exogenous surfactant distribution patterns at the lobar level between the two surfactant-treated groups, distribution histograms calculated for 10-g lung pieces revealed the Neb Surf animals had significantly more pieces within 25% of the mean value of 1.0 (42.7 +/- 6.9%) than did Inst Surf animals (20.8 +/- 5.5%) (P < 0.01). Exogenous surfactant therapy improved lung function with significantly different quantities of surfactant deposited in lung tissue for the two delivery methods evaluated.

Aerosols↗
PubMed1993

Lung responses to ultrasound-guided fetal treatments with corticosteroids in preterm lambs.

Maternal corticosteroid treatments augment lung function in the human preterm infant. However, not all fetuses respond, the response requires > or = 48 h of exposure, and multiple maternal doses expose the mother to potential risks. To evaluate the potential of direct fetal therapy, we used ultrasound to direct fetal intramuscular or intravascular injections of corticosteroids or saline in sheep and subsequently delivered the preterm lambs at 128 days gestational age to assess postnatal lung function. Relative to saline-injected controls, 0.5 or 2 mg/kg betamethasone given as a single intramuscular dose 48 h before delivery increased compliance and the efficiency of ventilation (as measured by an indicator that included ventilatory pressures and CO2 values) nearly twofold (P < 0.05). Lung volumes, measured from deflation pressure-volume curves, also increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary interstitial emphysema in 5 of 13 lambs, suggesting adverse effects. An intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of 0.1 mg/kg betamethasone had no effect on postnatal lung function. In separate studies, the 2 mg/kg dose improved all indicators of lung function almost twofold after only 24 h of fetal exposure and delivery at 128 days gestational age (P < 0.01). There was a dose-dependent suppression of the postnatal cortisol surge in treated animals, although fetal treatment did not alter cord cortisol levels. Single-dose fetal hormone treatments can cause large and rapid improvements in postnatal lung function in preterm lambs.

Adrenal Cortex Hormones↗
PubMed1993

Surfactant and the adult respiratory distress syndrome.

ARDS includes a complex series of events leading to alveolar damage, high permeability pulmonary edema, and respiratory failure. The endogenous pulmonary surfactant system is crucial to maintaining normal lung function, and only recently has it been appreciated that alterations in the surfactant system significantly contributed to the pathophysiology of the lung injury of patients with ARDS. Through a combination of analyzing BAL samples from patients with ARDS and extensive animal studies, there have been significant insights into the variety of surfactant abnormalities that can occur in injured lungs. These include altered surfactant composition and pool sizes, abnormal surfactant metabolism, and inactivation of alveolar surfactant by serum proteins present within the airspace. Positive effects of exogenous surfactant administration on acute lung injury have been reported. There is now a prospective, randomized clinical trial evaluating the efficacy of aerosolized exogenous surfactant in patients with ARDS. This trial has demonstrated improvements in gas exchange and a trend toward decreased mortality in response to the surfactant. Despite these encouraging results, there are multiple factors requiring further investigation in the development of optimal surfactant treatment strategies for patients with ARDS. Such factors include the development of optimal surfactant delivery techniques, determining the ideal time for surfactant administration during the course of injury, and the development of optimal exogenous surfactant preparations that will be used to treat these patients. With further clinical trials and continued research efforts, exogenous surfactant administration should play a useful role in the future therapeutic approach to patients with ARDS.

Animals↗
PubMed1993

Treatment responses to surfactants containing natural surfactant proteins in preterm rabbits.

The in vivo function of surfactants reconstituted using natural surfactant lipid and protein constituents was evaluated in 27-day-gestation preterm rabbits. The animals were treated with protein-free surfactant lipids (LH-20), LH-20 + 5% SP-A, LH-20 + 1% SP-B, LH-20 + 1% SP-C, LH-20 + 5% SP-A + 1% SP-B + 1% SP-C (SP-ABC), natural sheep surfactant, or 4 ml/kg 0.45% NaCl (control) and then ventilated with tidal volumes of 8 ml/kg and 3 cm H2O positive end-expiratory pressure (PEEP). Ventilatory pressures (peak pressures minus PEEP) and dynamic compliances of the LH-20 + SP-C rabbits were greater (p < 0.01) than those of control, LH-20, and LH-20 + SP-A groups but lower (p < 0.05) than in the LH-20 + SP-B, LH-20 + SP-ABC, and sheep surfactant groups. Recoveries of intravascular labeled albumin in the lungs were comparable in the LH-20 + SP-B, LH-20 + SP-C, LH-20 + SP-ABC, and sheep surfactant groups and less (p < 0.01) than in LH-20 + SP-A rabbits, which had lower (p < 0.05) recoveries than did the control and LH-20 groups. The postventilation pressure-volume curves for LH-20 + SP-B and LH-20 + SP-ABC rabbits had significantly lower opening pressures, larger maximal lung volumes, and larger retained volumes on deflation relative to the LH-20 + SP-C, LH-20, and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Physiologic responses and distribution of aerosolized surfactant (Survanta) in a nonuniform pattern of lung injury.

The underlying pattern of lung injury in patients with the adult respiratory distress syndrome (ARDS) may be nonuniform. The purpose of this study was to document whether a nonuniform pattern of lung injury influences treatment responses to aerosolized exogenous surfactant. Adult sheep underwent either total lung lavage (Tot Lav) or partial lung lavage (Par Lav) with saline, and they were subsequently mechanically ventilated for 90 min. Previous studies confirmed that this procedure induces acute lung injury. Partial lavage animals had their right upper lobe (RUL) protected from lavage by balloon obstruction of the RUL bronchus, and the occlusion was removed prior to the ventilatory period. Animals in both groups were then treated with either nebulized surfactant (Neb Surf) or nebulized saline (Neb Saline) for a further 180 min. PaO2, PaCO2, and peak inspiratory pressure significantly improved for the Tot Lav-Neb Surf animals compared with pretreatment values (p < 0.01). There were no significant changes for the other three groups (Tot Lav-Neb Saline, Par Lav-Neb Surf, Par Lav-Neb Saline). Lobar distribution of aerosolized [3H]surfactant in lung tissue revealed that Par Lav-Neb Surf animals had approximately 50% of the total surfactant recovered from the RUL compared with approximately 20% recovery from the RUL in the Tot Lav-Neb Surf group. The preferential deposition of exogenous surfactant in the RUL of the Par Lav-Neb Surf group resulted in significantly less surfactant deposited in other injured regions of the lung (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1993

Changes in exogenous surfactant in ventilated preterm lamb lungs.

Preterm lambs were treated with either a surfactant from bovine lung (Survanta) or three synthetic surfactants (Exosurf), a 69:22:9 mixture of dipalmitoylphosphatidylcholine, phosphatidylglycerol, and palmitic acid prepared by heat annealing (Lipid Mixture 1) or with glass beads (Lipid Mixture 2). After 5 h of ventilation, large and small aggregate surfactant fractions were isolated from alveolar washes by centrifugation. SP-A was used as an indicator for the association of endogenous surfactant components with the treatment surfactants. The large aggregate fraction from Survanta-treated lambs contained more SP-A than did the fractions from the lambs treated with the other surfactants (p < 0.05). The surfactants used to treat the sheep and the large aggregate surfactants from alveolar washes increased compliances when tested in surfactant-deficient, immature rabbits, relative to that in control animals. The large aggregate fractions in alveolar washes from lambs treated with Survanta, Lipid Mixture 1, and Lipid Mixture 2 improved compliances in the preterm rabbits to a greater extent than did the surfactants used to treat the lambs. The small aggregate fractions were inactive as surfactants. The function of exogenous surfactant can be improved after exposure to the preterm lung. The improvement may result from the association of exogenous surfactant with components of endogenous surfactant.

Analysis of Variance↗
PubMed1993

Surfactant metabolism.

Alveolar surfactant pool sizes are small in the preterm animal with RDS, and these pool sizes probably increase to approximate those found in preterm animal without RDS by 3 to 4 days after birth. De novo synthesis and secretion of surfactant phospholipids are slow processes. Therefore, surfactant treatments are the only way to acutely increase the pool size. Surfactant phospholipids are very slowly catabolized in the preterm lung. The surfactant phospholipids used for treatment rapidly associate with lung tissue and are processed by recycling through lamellar bodies within type II cells. Surfactant proteins already present within the preterm lung can associate with the exogenous surfactant. These proteins have metabolic pathways quite different from those for the lipids. Surfactant treatments do not seem to interfere with endogenous metabolic pathways for surfactant synthesis and secretion. Surfactant treatments of infants with RDS are beneficial in part because of the favorable metabolism characterized by a preterm lung that can recycle surfactant and does not catabolize the exogenous surfactant.

Animals↗
PubMed1993

Surfactant metabolism.

Based on these metabolic studies of surfactant lipids in term lambs, in preterm lambs not treated with surfactant, and in preterm lambs that have been surfactant-treated, the following is a synthesis of the overall metabolism of surfactant. Preterm surfactant-deficient lungs seem to have all the synthetic and secretory pathways for surfactant phosphatidylcholine. Secretory kinetics are slow in preterm relative to term animals. Recycling pathways are active in the preterm lung, and surfactant used for treatment can be recycled. The major difference between the preterm or term lung and the adult lung is that there is almost no surfactant phosphatidylcholine catabolism in the developing lung. All assessments of surfactant metabolism are complicated by the different forms of surfactant within the airspaces that represent different functional surfactant pools. SP-A has secretory and reuptake kinetics quite different than those for phosphatidylcholine. De novo synthesized SP-A is secreted independently of lamellar bodies and may associate with surfactant lipids during the formation of tubular myelin. Surfactant treatments do not adversely affect endogenous synthetic and secretory phospholipid pathways by feedback inhibition. Therefore, surfactant treatments have two primary effects on the preterm lung: physiological effects related to surface properties, and metabolic effects resulting from the exogenous surfactant phospholipids functioning as substrate for the recycling pathways.

Animals↗
PubMed1992

Platelet-activating factor antagonists decrease lung protein leak in preterm ventilated rabbits.

OBJECTIVE: The preterm ventilated lung is characterized by an increased protein leak from the pulmonary vascular spaces into the air spaces, which interferes with lung function and plays a role in neonatal respiratory distress syndrome. To investigate the role of platelet-activating factor in this process, platelet-activating factor antagonists were given to preterm ventilated rabbits. STUDY DESIGN: New Zealand White rabbits were delivered on day 28 of 31 days' gestation. Each rabbit pup received saline solution or one of two platelet-activating factor antagonists and were ventilated for 30 minutes with measurement of compliance, surfactant pool size, and protein leak into and out of the lung. Statistical analysis was performed with analysis of variance followed by Student-Newman-Keuls correction for multiple comparisons. RESULTS: There were no differences in lung compliance, surfactant pool size, or protein leak out of the air spaces among any of the groups. Treatment with the platelet-activating factor antagonists decreased the protein leak into the air spaces by greater than 50% and into the lung as a whole by 40% (p less than 0.01). CONCLUSION: Platelet-activating factor plays a role in the protein leak seen in the preterm lung, which contributes to neonatal respiratory distress syndrome.

Animals↗
PubMed1992

Surfactant protein A metabolism in preterm ventilated lambs.

Surfactant protein A (SP-A) metabolism was studied in vivo in 33 preterm ventilated lambs at 138 +/- 1 days gestational age by measuring recoveries of exogenously administered surfactant containing both radiolabeled SP-A and labeled saturated phosphatidylcholine (Sat PC) given via the trachea at birth. Endogenously secreted SP-A was also labeled with [35S]methionine and followed over 24 h. The exogenously labeled SP-A left the alveolar pool more rapidly than did Sat PC over the first 5 h of life (P less than 0.05), and both exogenously labeled SP-A and Sat PC were detected within lamellar bodies by 2 h, indicating uptake from the airspaces. The quantity of SP-A in alveolar washes increased about twofold from birth to 5 h of age, whereas alveolar Sat PC pools were constant over 24 h. The SP-A endogenously labeled with [35S]methionine was recovered at highest specific activities in the alveolar washes at 10 and 45 min after birth with no labeled SP-A detectable in lamellar body fractions until 2 h. The curve for endogenous SP-A labeling of lamellar bodies was similar to that for exogenous labeling, indicating that SP-A was initially secreted by a pathway independent of lamellar bodies with subsequent SP-A labeling of lamellar bodies. The kinetics of SP-A metabolism were very different than for Sat PC in preterm lambs.

Animals↗