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Biomedical subjects

H C Jacobs

Publications and source records attributed to H C Jacobs.

31 records · Page 2Linked to original sources
PubMed1989

Pulmonary function tests and fluid balance in neonates with chronic lung disease during dexamethasone treatment.

Pulmonary function tests and fluid balance were measured serially during treatment with dexamethasone in seven ventilator-dependent, 14- to 27-day-old infants. The infants showed no improvement in respiratory status during the prior 5 days. Birth weights ranged from 540 to 900 g, with gestational ages of 24 to 26 weeks. The decision to treat the infants with dexamethasone was made by the clinical team. Pulmonary function tests were performed prior to the first dose and then every 12 hours until extubation. Significant differences were first seen after only 12 hours of treatment. Five infants were extubated within 48 hours of starting therapy. Before extubation at 48 hours, changes were found in dynamic compliance (74% increase), total pulmonary resistance by midvolume and regression methods (38% and 35% decreases, respectively), and expiratory time constant (49% increase), with P less than .01 in all cases. An increase in urine output was also observed in the first 12 hours. Improvements in chronic lung disease produced by dexamethasone are rapid and may result from dexamethasone-induced pulmonary fluid shifts.

Bronchopulmonary Dysplasia↗
PubMed1988

Reutilization of surfactant phosphatidylglycerol and lysophosphatidylcholine by adult rabbits.

Adult rabbits reutilize the phosphatidylcholine (PC) of surfactant much less efficiently than developing rabbits (22% vs. 95%). Comparisons of reutilization efficiency of other components of surfactant in adult rabbits have not been determined. We injected adult rabbits intratracheally with [3H]dipalmitoylphosphatidylcholine (DPPG) mixed with [14C]lysophosphatidylcholine (lysoPC) and natural surfactant or [14C]DPPC mixed with [3H]dipalmitoylphosphatidylglycerol (DPPG) and natural surfactant. Recovery in the alveolar wash and lamellar bodies of labelled DPPC, lysoPC and DPPG was determined at different times after injection. By plotting the ratio of [3H]DPPG to [14C]DPPC in the alveolar wash versus time after injection we found that phosphatidylglycerol was reutilized with an efficiency of only 0-7% which was much less than the reutilization of PC in these animals. At early times after injection, adult rabbits injected with [14C]lysoPC had a ratio of [14C]PC in their alveolar wash to lamellar bodies that was larger than 1.0. By comparison, 3-day old rabbits injected intratracheally with [14C]lysoPC had a ratio of [14C]PC in alveolar wash to lamellar bodies less than 1.0 at the earliest times measurable. Thus adult rabbits demonstrate a pathway for accumulation of PC in their alveolar space prior to its appearance in lamellar bodies. This was not detected in developing rabbits. As in developing rabbits, adult rabbits reutilize the phosphatidylglycerol of surfactant less efficiently than the PC of surfactant.

Aging↗
PubMed1987

Thresholds for physiological effects of plasma catecholamines in fetal sheep.

To clarify the physiological role for the marked increases in circulating norepinephrine (NE) and epinephrine (E) that occur at birth, we performed graded infusions of NE and E in preterm (131 days) and full-term (142 days) fetal sheep. A variety of hemodynamic, metabolic, and endocrine responses to stepwise increases in plasma catecholamine levels were analyzed by computer-based graphical analysis of the dose-response curves. We determined the "threshold" value or minimum plasma concentration necessary to produce discernible effects. We observed increases in systolic blood pressure, diastolic blood pressure, and dP/dt beginning at plasma concentrations of 500-800 pg/ml of NE or E. In contrast, increases in plasma free fatty acid and glucose levels were observed at E concentrations as low as 50-100 pg/ml. Full-term animals had generally lower thresholds and higher peak responses than preterm animals. Because these thresholds for infused NE and E are well within the range of plasma catecholamine values seen at birth, these results underscore the importance of circulating catecholamines in the events of neonatal adaptation.

Animals↗
PubMed1987

Betamethasone increases pulmonary compliance in part by surfactant-independent mechanisms in preterm rabbits.

Antenatal exposure to corticosteroids is known to increase the pulmonary compliance of preterm animals. We wished to determine whether this was due solely to alteration in lung surfactant content. Rabbit does were injected with either vehicle alone or betamethasone on days 25 and 26 of gestation. Fetuses were delivered at 27 days and given either 50% lactated Ringer's or intratracheal natural surfactant prior to their first breath. Fetuses were mechanically ventilated at a tidal volume of 12 ml/kg for 60 min with periodic compliance measurements. Following ventilation an alveolar lavage was collected for phosphatidylcholine determination. Some fetuses did not undergo ventilation but had saline compliance studies instead. Fetuses given intratracheal surfactant had a higher dynamic compliance than fetuses exposed to antenatal corticosteroids (0.55 +/- 0.01 versus 0.48 +/- 0.02 ml/cm H2O/kg, respectively). Fetuses exposed to antenatal corticosteroids and given intratracheal surfactant had a dynamic compliance (0.66 +/- 0.02) that was greater than those exposed to either single therapy. This was found despite an alveolar surfactant content equal to that in fetuses receiving intratracheal surfactant alone. Saline compliance at birth was significantly greater for fetuses exposed antenatally to steroids. These data imply the existence of a nonsurfactant mechanism by which antenatal corticosteroids increase fetal pulmonary compliance.

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

Corticosteroids and intratracheal surfactant both alter the distribution between the airways and lung tissue of intratracheally administered radiolabeled phosphatidylcholine in the preterm rabbit.

Developmental differences exist regarding quantitative aspects of surfactant phosphatidylcholine clearance from the alveolar space and its subsequent reutilization. We wished to further extend observations of this nature to prematurely delivered rabbits undergoing mechanical ventilation. In addition we tested the hypothesis that prenatal corticosteroid exposure and/or intratracheal surfactant at birth would produce alterations in the lung's clearance of phosphatidylcholine from the airways. Pregnant does were injected with either Ringer's lactate or betamethasone on days 25 and 26 of gestation. Fetuses were delivered at 27 days and given by intratracheal injection either surfactant or one-half strength Ringer's lactate, both of which were trace labeled with [3H]phosphatidylcholine. Fetuses then underwent mechanical ventilation for periods of time ranging from 10 to 120 min. Following ventilation, alveolar lavage and lung tissue were examined to determine the distribution of [3H]phosphatidylcholine between these two compartments. Antenatal corticosteroid exposure was associated with decreased recovery of the radiolabel from the alveolar space and increased recovery of the label from the lung tissue in comparison to control fetuses. Intratracheal surfactant was associated with persistence of the radiolabel within the alveolar space. Therapy with both of these modalities produced a radiolabel distribution that resembled that seen in fetuses receiving intratracheal surfactant alone.

Adrenal Cortex Hormones↗