Biomedical subjects

A H Jobe

Publications and source records attributed to A H Jobe.

At least 163 records · Page 9Linked to original sources

PubMed1989

Surfactant phosphatidylcholine metabolism and surfactant function in preterm, ventilated lambs.

Preterm lambs were delivered at 138 days gestational age and ventilated for periods up to 24 h in order to study surfactant metabolism and surfactant function. The surfactant-saturated phosphatidylcholine pool in the alveolar wash was 13 +/- 4 mumol/kg and did not change from 10 min to 24 h after birth. Trace amounts of labeled natural sheep surfactant were mixed with fetal lung fluid at birth. By 24 h, 80% of the label had become lung-tissue-associated, yet there was no loss of label from phosphatidylcholine in the lungs when calculated as the sum of the lung tissue plus alveolar wash. De novo synthesized phosphatidylcholine was labeled with choline given by intravascular injection at 1 h of age. Labeled phosphatidylcholine accumulated in the lung tissue linearly to 24 h, and the labeled phosphatidylcholine moved through lamellar body to alveolar pools. The turnover time for alveolar phosphatidylcholine was estimated to be about 13 h, indicating an active metabolic pool. A less surface-active surfactant fraction recovered as a supernatant after centrifugation of the alveolar washes at 40,000 x g increased from birth to 10 min of ventilation, but no subsequent changes in the distribution of surfactant phosphatidylcholine in surfactant fractions occurred. The results were consistent with recycling pathway(s) that maintained surface-active surfactant pools in preterm ventilated lambs.

Animals↗

PubMed1989

Relationship between alveolar saturated phosphatidylcholine pool sizes and compliance of preterm rabbit lungs. The effect of maternal corticosteroid treatment.

The relationship between alveolar saturated phosphatidylcholine pool size and compliance was evaluated in control and maternal corticosteroid-treated 27-, 28-, and 29-day gestational age preterm ventilated rabbits. Surfactant pool sizes below about 0.7 mumol saturated phosphatidylcholine/kg body weight did not alter compliance in either group. Compliance increased to values comparable to surfactant-treated or term newborn rabbits over a narrow range of saturated phosphatidylcholine pool sizes from about 0.7 to 1.2 mumol/kg for corticosteroid-treated rabbits and from about 0.9 to about 2.3 mumol/kg for control rabbits (p less than 0.01). When these results are compared with those from surfactant-treated rabbits, almost an order of magnitude less endogenous surfactant than exogenous surfactant is needed to alter compliance in preterm ventilated rabbits.

Animals↗

PubMed1989

Gestational effects of corticosteroids and surfactant in ventilated rabbits.

Maternal corticosteroid treatments decreased lung protein leaks and increased the compliance responses to exogenous surfactant in 27-day preterm rabbits. We asked if maternal corticosteroid treatments at different gestational ages might alter these responses. Pregnant does were given 0.1 mg/kg betamethasone 48 and 24 h before study of the rabbits at 27, 28, and 29 days of gestational age and term newborns at 31 days of gestational age. Alternate rabbits at each gestation were treated with 50 mg/kg surfactant after delivery. Alveolar saturated phosphatidylcholine pool sizes increased with gestation similarly in control and corticosteroid-treated groups. Corticosteroids improved compliance relative to control values at 29 days of gestational age in animals not treated with surfactant and improved the compliance response to surfactant treatment at 27 and 28 days of gestational age. Corticosteroids decreased the leak of radiolabeled albumin to the lungs and alveolar washes at all preterm gestations with a maximum decrease to 16% of the control value at 29 days of gestation. Surfactant decreased this protein leak more effectively than did corticosteroids at the earlier gestations. There were potentially beneficial effects of corticosteroids either alone or together with surfactant at all preterm gestations studied. No protein leak or compliance effects of either treatment were noted in the term newborns.

Animals↗

PubMed1989

Surfactant metabolism during hyperventilation of newborn lambs with atrial right to left shunts.

We studied the effect on surfactant metabolism of 8 h of mechanical ventilation at tidal volumes of 13 +/- 0.3 ml/kg and very high tidal volumes of 28 +/- 1.5 ml/kg, with and without added CO2, in the presence of an atrial right to left shunt in 4- to 8-day-old lambs. Similarly aged, spontaneously breathing lambs were used as controls. Right to left atrial shunts were created by inflating a balloon in the right atrium after a Rashkind atrial septostomy, thus creating a stable, easily controlled atrial shunt. Radiolabeled surfactant phospholipid precursors were used to probe incorporation into and secretion of surfactant phosphatidylcholine, whereas intratracheally administered labeled natural surfactant was used to evaluate alveolar clearance. Protein leak from the vascular space to the lungs was measured using radioactive iodine-labeled albumins. At the end of the 8-h study period, tissue association of alveolar surfactant was significantly increased to 63% in the mechanically hyperventilated lambs as compared to 44% in those lambs mechanically ventilated but not hyperventilated (p less than 0.05) and to 39% in the spontaneously breathing control animals (p less than 0.05). No increased surfactant secretion or decreased compliance was detected with hyperventilation. However, the lambs had very large surfactant-saturated phosphatidylcholine pool sizes, and a large portion (50%) was already in the alveolar pool, even in the spontaneously breathing lambs. Precursor incorporation into saturated phosphatidylcholine was similar in all groups, and very low and comparable protein leaks were seen in the different groups of lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Recovery of treatment doses of surfactants from the lungs and vascular compartments of mechanically ventilated premature rabbits.

Premature rabbits delivered by cesarean section at 28 d of gestation were each given intratracheally 75 mg/kg of radiolabeled preparation of either natural rabbit surfactant, natural calf surfactant, or surfactant-TA. Each newborn rabbit was ventilated for up to 6 h in a ventilator-plethysmograph with individual adjustments of peak inspiratory pressures to attain tidal vol of 12-15 mL/kg body wt. Dynamic compliances were about 0.7-0.9 mL/cm H2O. kg after treatment with the three surfactants and did not deteriorate during the 6-h study. Rabbits were randomly studied at 0.5, 1.5, 3, 4.5, and 6 h of age for the recovery of the labeled surfactant phosphatidylcholine in the total lungs (alveolar wash plus postlavage lung tissue). The labeled phosphatidylcholine was cleared from the total lungs of rabbits treated with natural rabbit or calf surfactants at comparable rates of about 25%/6 h. In contrast, the clearance rate of surfactant-TA phosphatidylcholine from the total lungs was not significantly different from 0. Lipids from rabbit surfactant that had been administered intratracheally were only minimally present in the blood and liver. In other similarly treated rabbits, the lipids from radiolabeled rabbit surfactant and liposomes of dipalmitoylphosphatidylcholine that had been injected intravenously were recovered in blood and liver in substantial quantities. These studies documented significant losses of rabbit and calf surfactant phosphatidylcholine but not surfactant-TA phosphatidylcholine from the lungs of preterm ventilated rabbits. The losses were not explained by surfactant losses to the vascular compartment.

Animals↗

PubMed1989

Hemodynamic and neuroendocrine adaptations of the preterm lamb left ventricle to acutely increased afterload.

The birth process is associated with dramatic alterations of left ventricular (LV) volume loading, pressure loading, and contractile state. The preterm LV has considerable volume loading reserve. We have assessed neuroendocrine and related hemodynamic responses of the preterm lamb LV at 0.8 gestation during acute pressure loading within the first 2-4 h after birth. We measured plasma catecholamines and hemodynamic and cineangiocardiographic parameters of LV pump performance and contractility at basal levels and during rapid LV pressure loading by partial balloon obstruction of the ascending aorta before and after propranolol. A relatively high level of propranolol (3 mg/kg) was required to produce beta-adrenoceptor blockade associated with reduction of heart rate and blood pressure, but after atrial pacing there was no detectable difference of basal LV pump performance or contractility at comparable heart rate, preload, and afterload. The LV pump performance was maintained and plasma catecholamines and LV contractility were increased when aortic systolic pressure was augmented 60% over baseline. The increased contractile state at greater afterload was minimally blunted by propranolol. Thus the preterm LV is relatively hypercontractile soon after birth and is capable of an integrated augmentation of pump performance and contractile state during pressure loading. These findings are relevant to the maintenance of adequate LV performance and successful adaptation to the acute alterations of afterload associated with the transitional circulation at birth.

Animals↗

PubMed1989

Lung maturational agents and surfactant treatments: are they complementary in preterm infants?

Maternal corticosteroid treatments are used by many obstetric services in selected cases of preterm labor to induce lung maturation. This maturational strategy, however, has not received universal acceptance and often is used without much enthusiasm because such treatments do not prevent respiratory distress syndrome (RDS) in many infants. This article develops the thesis that the effects of maternal corticosteroid treatments are not primarily on the surfactant system, but rather on other aspects of lung development. The question posed by the title has not been answered by published clinical trials, but a growing body of experimental research with animal models indicates that strategies to induce lung maturation and to treat infants with surfactant will be complementary. An added benefit of the use of lung maturational agents should be the induction of maturational responses in other organ systems in the fetus.

Adrenal Cortex Hormones↗

PubMed1988

Lysophosphatidylcholine uptake and metabolism in the adult rabbit lung.

Tracer quantities of 3H-labeled lysoPC and 32P-labeled natural rabbit surfactant were given intratracheally via a bronchoscope and [14C]palmitate was given intravenously to 25 rabbits with labeled PC and lysoPC measured in the alveolar wash, lung homogenate, lamellar bodies and microsomes at five times from 10 min to 6 h after tracheal injection. Surprisingly, only 31% of the administered lysoPC remained in its original form in the total lungs (alveolar wash + lung homogenate) by 10 min, of which 77% was in the alveolar wash. Meanwhile, by 10 min an additional 37% was already converted to PC, of which more than 98% was in the lung homogenate. LysoPC continued to be rapidly and efficiently converted to PC, with 62% conversion measured at 3 h. The converted lysoPC initially appeared with high specific activity in microsomes, then in lamellar bodies, and finally in the alveolar wash. The intravascular palmitate labeled lung PC had similar specific activity-time profiles in the subcellular fractions, while intratracheally administered natural rabbit surfactant had a constantly low specific activity in microsomes and much higher specific activities in lamellar bodies and alveolar wash. Another 25 rabbits received intratracheal lysoPC labeled in both the choline and palmitate moieties and then were studied from 1 to 24 h after tracheal injection. The ratio of the palmitate to choline labels indicated uptake and conversion to PC primarily by direct acylation rather than transacylation and by intact reuptake and conversion rather than breakdown and resynthesis. LysoPC is an attractive 'metabolic probe' of surfactant metabolism which undergoes very rapid and efficient intracellular conversion to PC via a subcellular pathway that parallels the remodeling and de novo synthetic pathways.

Animals↗

PubMed1987

Effects of maternal treatment with corticosteroids, T3, TRH, and their combinations on lung function of ventilated preterm rabbits with and without surfactant treatments.

Pregnant does were treated with betamethasone, T3, TRH, or combinations of betamethasone plus T3 or TRH using doses of each agent known to effect lung maturation. Preterm rabbits were then delivered at 27 days gestational age, half of each group was treated with Surfactant TA, and the rabbits were ventilated in a ventilator-plethysmograph system such that tidal volumes were regulated to mean values of 12 to 13 ml/kg. At 30 min of age when mean PCO2 values for the study groups were between 33 and 42 mm Hg, lung function of each rabbit was evaluated by the peak inspiratory pressure needed to achieve the desired tidal volume, by compliance, and by the ventilation efficiency index. These measures of lung function showed no benefit of corticosteroids or T3 in the absence of surfactant, whereas TRH significantly improved lung function. Although surfactant treatment improved lung function in all groups, the best effect after a single hormone treatment was with corticosteroids. The combined use of corticosteroids and TRH in surfactant-treated animals resulted in the best overall responses. The leak of protein into and out of the lungs was measured with radiolabeled albumins. The leak decreased as peak ventilatory pressures decreased in all groups and decreased with surfactant treatments of all groups. Corticosteroids decreased the protein leak into the airways more than could be accounted for by the effects of corticosteroids on ventilatory pressures alone (p less than 0.01). None of the hormone treatments significantly increased the saturated phosphatidylcholine pool sizes from the low values noted in the control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Reutilization of surfactant phosphatidylcholine in adult rabbits.

32P-saturated phosphatidylcholine was added to [3H]choline-labeled natural surfactant and the mixture was injected intratracheally into 87 adult rabbits. The rabbits were also given [14C]palmitate intravenously at the same time. Rabbits were killed in groups from 10 min to 72 h after injection. In each rabbit we measured the total recovered [3H]phosphatidylcholine (PC) in the alveolar wash, the ratio of [3H]PC to [32P]PC in the alveolar wash, and the specific activity of [14C]PC in the alveolar wash and lamellar bodies. Values were averaged for all rabbits killed at the same times and smooth curves were fit to the data by computer. From the intravenous [14C]palmitate data we calculated a turnover time for alveolar PC of 6.0 h. From the intratracheal labeling data, we calculated a turnover time for alveolar PC of 5.7 h and determined that alveolar PC was reutilized at an efficiency of only 23%. We also concluded that this reutilization occurred as intact molecules.

Animals↗

PubMed1985

Reutilization of phosphatidylglycerol and phosphatidylethanolamine by the pulmonary surfactant system in 3-day-old rabbits.

Developing rabbits reutilize the phosphatidylcholine of surfactant with an efficiency of about 95%. The efficiency of reutilization of other components of surfactant have not been determined. 3-day-old rabbits were injected intratracheally with [3H]dipalmitoylphosphatidylcholine (DPPC) mixed with unlabeled natural surfactant and either disaturated [32P]phosphatidylglycerol (DSPG) or [14C]dipalmitoylphosphatidyl-ethanolamine (DPPE). The recovery of [3H]DPPC, [14C]DPPE, and [32P]DSPG in the alveolar wash was measured at different times after injection. By plotting the ratio of [32P]DSPG to [3H]DPPC or [14C]DPPE to [3H]DPPC counts/min in the alveolar wash vs. time after injection we showed that these two phospholipids are reutilized less efficiently than phosphatidylcholine. Based on other studies, several assumptions were made about the kinetics of surfactant phosphatidylethanolamine and phosphatidylglycerol. From the slopes of the semilog plots of total [14C]DPPE and total [32P]DSPG counts/min in the alveolar wash vs. time and these assumptions, we determined that these two phospholipids were reutilized at an efficiency of only 79%.

Age Factors↗

PubMed1985

Normalization of arterial blood gases after treatment of surfactant-deficient lambs with Tween 20.

Pulmonary surfactant (PS) is capable of lowering surface tension at an air-water interface to less than 10 dynes/cm. This property of PS is believed to be important for normal lung function. We tested the detergent Tween 20, which cannot lower surface tension at an air-water interface to less than 25 dynes/cm, for its ability to promote reasonable gas exchange in surfactant-deficient lambs delivered prematurely at 120 to 124 days gestation. Lambs were treated at birth with 75 mM NaCl (control), 5% Tween 20 in 75 mM NaCl, or PS in 75 mM NaCl and placed on infant ventilators. Control lambs had poor oxygenation and were in respiratory failure at 30 min of age (arterial PCO2 of 75.8 +/- 11 mmHg (mean +/- SE)) despite peak inspiratory pressures (PIP) of 32 +/- 0.7 cm H2O. Pulmonary surfactant treatment allowed adequate ventilation with a PIP of 23.8 +/- 1.2 cm H2O. Tween treatment also allowed adequate ventilation with a PIP of only 27 +/- 1.3 cm H2O. Minimal surface tensions in alveolar washes of control and Tween-treated lambs were 28.7 +/- 1.3 and 26.7 +/- 2.3 dynes/cm, respectively, compared with less than 10 dynes/cm for PS-treated lambs. Thus, Tween 20 did not alter the alveolar wash minimal surface tension when compared with that of the control animals but it did significantly improve gas exchange and lung compliance.

Animals↗

PubMed1984

[Adrenal epinephrine and the regulation of pulmonary surfactant release in neonatal rabbits].

Adrenergic mechanisms influence surfactant metabolism; however the nature and importance of catechol-mediated regulation is unclear. We designed experiments to assess the role of endogenous adrenal epinephrine (E) synthesis in neonatal alveolar surfactant release. We administered the experimental adrenal epinephrine synthesis inhibitor SKF 29661 to pregnant rabbits to reduce fetal adrenal E content. Surfactant release was measured as total alveolar phosphatidylcholine (PC) content recovered by a thorough alveolar wash performed on animals sacrificed at birth and at 1 h of age. At a maternal dose of 100 mg/kg/day, SKF 29661 caused a 57% reduction in fetal adrenal E content (p less than .01), which was associated with a 40% reduction in alveolar PC at birth and a 23% reduction in alveolar PC at 1 h of age (p less than .01). Moreover, adrenal E correlated positively with total alveolar PC content (p less than .001). These results suggest that in the neonatal period, the ability of the fetal adrenal gland to synthesize E for secretion plays a role in the regulation of pulmonary surfactant release.

Adrenal Glands↗

PubMed1983

Left ventricular performance and regional blood flows before and after ductus arteriosus occlusion in premature lambs treated with surfactant.

The hemodynamic consequences of patent ductus arteriosus (PDA) were studied during the first few hours of life (1.9 +/- 0.7 hours) in 13 mechanically ventilated, surfactant-treated, preterm lambs (gestational age of 120-124 days). Cardiovascular pressures, left ventricular (LV) performance and regional blood flows were measured using cine left ventriculography and radionuclide-labeled microspheres before and after occlusion of the PDA with a catheter balloon. Before occlusion, the left-to-right shunt was 44 +/- 13%; after occlusion the shunt was negligible (2%). Heart rate (164 +/- 17 beats/min), LV end-diastolic pressure (5 +/- 3 mm Hg), ejection fraction (74 +/- 8%) and cardiac output (241 +/- 13 ml . min-1 . kg-1) were normal and did not change after ductus occlusion. However, "effective" systemic blood flow increased significantly after occlusion (130 +/- 53 vs 228 +/- 93 ml . min-1 . kg-1, p less than 0.001), as did blood flow to organs such as the brain, myocardium and gastrointestinal tract. The reduction of systemic blood flow in the presence of a left-to-right PDA shunt may be responsible for many early pathologic manifestations of the PDA "syndrome" of prematurity even in the absence of overt LV dysfunction.

Animals↗

PubMed1983

Surfactant pool sizes and severity of respiratory distress syndrome in prematurely delivered lambs.

To quantify the relationship between surfactant pool size and severity of respiratory disease, 21 lambs were delivered at 134 to 136 days gestational age and ventilated by varying only peak inspiratory pressure to maintain tidal volume at 6.2 +/- 0.3 ml/kg (mean +/- SE) and thus to control PCO2. Compliance measurements were used to quantify the severity of lung disease. After alveolar wash, surfactant phosphatidylcholine, saturated phosphatidylcholine, and minimal surface tensions were estimated. Compliance correlated linearly with saturated phosphatidylcholine pool size (r = 0.755, p less than 0.001). The mean minimal surface tension of the alveolar washes was 17.4 +/- 1.7 dynes/cm, and alveolar washes from lambs with more compliant lungs had lower minimal surface tensions than did washes from lambs with poorly compliant lungs (p less than 0.001). Lung tissue of all lambs contained similar amounts of saturated and total phosphatidylcholine, and in vitro rates of incorporation of labeled choline and palmitate into phosphatidylcholine in lung slices were similar, independent of severity of lung disease. The pool size of surfactant within the alveoli is an important determinant of lung disease in premature lambs; however, surface tension, tissue maturity, and other factors may contribute to the severity of the disease.

Animals↗

PubMedDate not supplied

Surfactant in the perinatal period.

Surfactant is now available for general clinical use in infants with RDS. While surfactant is effective, it does not prevent lung disease in many preterm infants because of other aspects of lung immaturity. In experimental models, corticosteroids alter the fetal lung by improving compliances, increasing lung volumes, decreasing pulmonary edema, and altering surfactant-compliance dose response curves. These effects are independent of changes in surfactant pools but augment the responses of the lungs to surfactant treatment. Optimal outcomes for the preterm require the combined use of fetal maturation strategies and postnatal surfactant.

Adrenal Cortex Hormones↗

PubMedDate not supplied

Preterm betamethasone treatment of fetal sheep: outcome after term delivery.

OBJECTIVES: Although antenatal corticosteroids improve outcomes for preterm newborns, negative effects could result if preterm delivery does not occur. We investigated whether betamethasone treatment of preterm fetal sheep would alter cardiovascular, renal, and lung function after delivery at term. METHODS: Preterm fetal lambs were randomized at 126-128 days' gestation to receive single doses of saline (n = 6) or 0.5 mg/kg betamethasone (n = 7) by ultrasound-guided fetal intramuscular injection. The lambs were delivered by cesarean at term, 20 days after fetal treatment, then ventilated for 4 hours to evaluate lung, cardiovascular, renal, and endocrine newborn adaptive responses, as well as responses to mild hypoxia. RESULTS: Body and organ weights (brain, lung, heart, kidney, adrenal) were similar in the two groups. Values for blood gases and pH, mean arterial pressures, heart rates, glomerular filtration rates, renal osmolar clearance, and plasma cortisol, angiotensin II, epinephrine, and norepinephrine levels were similar between groups for 3 hours after delivery and before hypoxia. A 20-minute period of mild hypoxia resulted in increases in catecholamines, arginine vasopressin, and atrial natruretic factor in both betamethasone-treated and control lambs. However, hypoxia did not alter cardiovascular or lung function in either group. After reversal of hypoxia, measured physiologic parameters did not differ between groups. Kidney Na, K-adenosine triphosphatase activity was significantly higher for the betamethasone-treated lambs. CONCLUSION: Preterm fetal betamethasone administration does not alter neonatal pulmonary, cardiovascular, renal, or endocrine physiology after term delivery or in response to mild hypoxia.

Animals↗

PubMedDate not supplied

Cumulative effects of repeated surfactant treatments in the rabbit.

The responses of the adult rabbit lung to multiple doses of surfactant after intratracheal injections of either natural calf surfactant or Surfactant-TA were evaluated. For each surfactant, four groups of 1.4-kg rabbits were studied: group 1 received 100 mg of surfactant containing isotopically-labeled dipalmitoylphosphatidylcholine; group 2 received the same labeled surfactant and then three tracheal injections of vehicle; group 3 received labeled surfactant and then three doses (100 mg) of unlabeled surfactant; group 4 was treated in the same way as group 3 except that the final dose was of the labeled surfactant. All rabbits were killed, and alveolar washes were recovered 24 h after the labeled surfactant dose had been given. The amount of labeled palmitate-saturated phosphatidylcholine (Sat PC) in alveolar washes did not change after multiple doses of calf surfactant, indicating that subsequent doses did not alter the clearance of previous doses. The four doses of calf surfactant increased the alveolar Sat PC pool size by a factor of 2.5 only when measured 6 h after the last dose, but the total lung Sat PC pool size doubled, indicating a loss of most of the surfactant Sat PC to the lung tissue. In contrast, Surfactant-TA increased the alveolar pool size by a factor of 4 after the single dose and by a factor of 11 after the multiple doses, and the percentage clearance of labeled Sat PC from the lungs decreased with multiple doses, indicating an effect of subsequent doses on the initial dose. The quantity of Sat PC cleared from the lungs increased by about a factor of 2 after the multiple doses of Surfactant-TA. Although repetitive surfactant doses changed alveolar and lung Sat PC pool sizes the quantity of Sat PC cleared from the lungs increased, and the lungs accommodated the large amount of surfactant without short-term adverse effects.

Animals↗