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Biomedical subjects

C E Patterson

Publications and source records attributed to C E Patterson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Substrate utilization in the perinatal lung.

Lung cellular metabolism is fundamental to both respiratory and nonrespiratory function. The lung has very little energy reserve and is highly dependent on circulating substrates. The pattern of substrate utilization is determined primarily substrate availability, competition between certain substrates, and the ability of lung cells for uptake and metabolism. The lung uses a number of substrates (glucose, lactate, fatty acids, choline, ketone bodies, and amino acids) as basic building blocks for synthesis, as energy-providing fuels, to provide NADPH for lipid biosynthesis, and for glutathione production. Since the availability of substrates, the cellular profile, the hormonal environment, and the physiological state of the lung are drastically altered during perinatal lung development, this review focuses on current knowledge of lung substrate utilization during this critical period. Because development of the surfactant system has been specifically linked to infant respiratory distress syndrome, the majority of investigations relate to substrate utilization for phospholipid synthesis. It is hoped that this review will outline basic principles for interpretation of information on perinatal substrate utilization, collate available data, and provide a stimulus for future research.

Aging↗
PubMed1989

Role of microvascular pressure in reactive oxygen-induced lung edema.

O2 radicals are important in the pathogenesis of acute lung injury. The purpose of this investigation was to determine the role that microvascular pressure plays in edema induced by reactive O2 species generated by xanthine oxidase. In isolated rat lungs perfused with Krebs buffer plus 4% albumin, 5 mM glucose, and 2 mM xanthine at constant flow (13 ml/min), addition of xanthine oxidase (0.02 U/ml) caused a progressive increase in both pulmonary arterial and microvascular pressure (double occlusion method), which preceded the onset of edema. Both the pressure rise and edema formation were blocked by catalase, suggesting that vascular injury was related to H2O2 production. Lungs not exposed to free radicals that had microvascular pressure elevated to match that of the xanthine oxidase-perfused lungs showed only a small, reversible (nonedematous) weight gain. Lungs exposed to xanthine oxidase but perfused at constant microvascular pressure (5 Torr, similar to control lungs) showed a significant delay in protein-rich edema formation. These data indicate that reactive O2 metabolites induced lung injury, which is accompanied by increased microvascular pressure. Although the rise in microvascular pressure was shown not to be essential for edema formation, it does play a role in acceleration of the rate of transvascular fluid loss.

Animals↗
PubMed1989

The role of activation of neutrophils and microvascular pressure in acute pulmonary edema.

Activated polymorphonuclear neutrophils (PMN) can mediate vascular injury in the lung. This study compared activated aggregate PMN (emboli) to activated PMN that were previously adhered to the microvasculature (non-embolic) in the isolated perfused rat lung. Permeability and microvascular pressure (Pmv), components of PMN-induced edema, were examined by continuous measurement of wet weight, pulmonary arterial and left atrial pressures, and by intermittent determination of double occlusion pressure. PMN that were activated with phorbol myristate acetate and then perfused into the lung formed aggregates that lodged primarily in the precapillary bed, increasing arterial resistance. Although these PMN had minimal direct contact with the capillary endothelium, edema rapidly developed and Pmv was progressively elevated. If PMN were allowed to adhere in the capillary bed, a minimal and nonprogressive increase in Pmv and lung weight occurred. When these adherent PMN were then activated, there was a progressive rise in both Pmv and lung weight. The free radical scavenger catalase prevented this edema formation but not the rise in pressure. In control lungs with matched elevation of Pmv, edema did not develop. In another group of lungs with activation of pre-adherent PMN in which Pmv was maintained at control levels, edema formation was greatly delayed. These data show that: (1) the activated PMN free radical products alone caused permeability injury in the lung because neither contact of the PMN with the capillary endothelium nor embolization was necessary, and (2) increased Pmv does not cause edema but greatly increases the rate of edema formation when the endothelium is injured.

Animals↗
PubMed1988

Regulation of fetal lung disaturated phosphatidylcholine synthesis by de novo palmitate supply.

Lung surfactant disaturated phosphatidylcholine (PC) is highly dependent on the supply of palmitate as a source of fatty acid. The purpose of this study was to investigate the importance of de novo fatty acid synthesis in the regulation of disaturated PC production during late prenatal lung development. Choline incorporation into disaturated PC and the rate of de novo fatty acid synthesis was determined by the relative incorporation of [14C]choline and 3H2O, respectively, in 20-day-old fetal rat lung explants and in 18-day-old explants which were cultured 2 days. Addition of exogenous palmitate (0.15 mM) increased (26%) choline incorporation into disaturated PC but did not inhibit de novo fatty acid synthesis, as classically seen in other lipogenic tissue. Even in the presence of exogenous palmitate, de novo synthesis accounted for 87% of the acyl groups for disaturated PC. Inhibition of fatty acid synthesis by agaric acid or levo-hydroxycitrate decreased the rate of choline incorporation into disaturated PC. When explants were subjected to both exogenous palmitate and 60% inhibition of de novo synthesis, disaturated PC synthesis was below control values and 75% of disaturated PC acyl moieties were still provided by de novo synthesis. These data show that surfactant disaturated PC synthesis is highly dependent on the supply of palmitate from de novo fatty acid synthesis.

Animals↗
PubMed1988

Protective role of sulfhydryl reagents in oxidant lung injury.

Recently there has been a great deal of interest in exploring possible ways to protect the lung from oxidant damage. Since sulfhydryl compounds are among the most important endogenous antioxidants, their therapeutic use has been proposed. Glutathione (GSH), the main intracellular nonprotein sulfhydryl, plays an important role in the maintenance of cellular proteins and lipids in their functional state. With oxidant stress, GSH acts to protect cell constituents as evidenced by increased turnover to GSSG, formation of mixed disulfides with proteins, utilization of NADPH, and utilization of glucose in the pentose pathway. When GSH is experimentally lowered (e.g., by protein deficiency or with diethylmaleate) the toxic effects of oxidant stress are exacerbated as evidenced by increased membrane and cell damage, pulmonary edema, and mortality. Several recent investigations have shown that sulfhydryl reagents (particularly N-acetyl cysteine, a cell-permeable GSH precursor) can provide significant protection against certain pulmonary toxins. N-acetyl cysteine reduced the lethal effects of 100% O2 in rats by 65%. Therefore, the therapeutic potential of sulfhydryl reagents in the treatment and prevention of oxidant injury and the mechanisms involved are an important direction for lung research.

Animals↗
PubMed1987

Cyclooxygenase metabolites contribute to oleic acid-induced lung edema by a pressure effect.

We investigated the role that lung-derived arachidonic acid metabolites play in the acute changes in pulmonary hemodynamics, airway function, and lung fluid balance following oleic acid-induced injury in the isolated blood free perfused lung. A bolus injection of oleic acid (OA) emulsion (12 mg) into the pulmonary artery caused a rapid increase in pulmonary arterial pressure, inspiratory pressure, and weight gain. These pathophysiologic changes were not due to emboli per se, but were correlated with release of the vaso- and broncho-constrictive prostanoids, thromboxane A2 (measured as thromboxane B2) and prostaglandin F2 alpha. The leukotrienes (C4, D4, and E4) and prostacyclin (measured as 6 keto-prostaglandin F1 alpha) were not released by OA injury. Ibuprofen, a cyclooxygenase inhibitor, blocked the release of the vasoconstrictive prostanoids and also attenuated the rise in pressures and the development of edema indicating an important functional role for the prostanoids in the fluid imbalance. Ibuprofen also attenuated the increase in bronchoalveolar lavage protein but the protein leak was not completely prevented, suggesting that OA-induced increases in protein permeability occurred independently of prostanoid or leukotriene action. These data indicate that OA-induced edema formation was greatly amplified by arachidonic acid mediated pressure increases.

Animals↗
PubMed1986

Fatty acid synthesis in the fetal lung: relationship to surfactant lipids.

The aims of this study were to investigate the control of fatty acid synthesis and its relationship to surfactant production in the fetal lung during alteration of hormonal and substrate conditions. Lung explants from 18 day fetuses (term = 22 days) which were cultured 2 days in the presence of 10 mM lactate showed parallel acceleration of de novo fatty acid synthesis (3H2O incorporation) and [14C]choline incorporation into disaturated phosphatidylcholine (DSPC) compared to culture of explants in glucose. Both the cultured and fresh explants were resistant to the classical short term (4 h) cAMP inhibition of fatty acid synthesis with 3 mM dibutyryl cAMP or 0.5 mM aminophylline. In the cultured explants short term cAMP elevation increased DSPC production, and long term (2 day) cAMP elevation caused a further increase in DSPC synthesis and also stimulated fatty acid synthesis. In cultured explants from 17 day fetuses, dexamethasone (0.1 microM) caused a synergistic increase with aminophylline in both fatty acid synthesis and DSPC production whereas, in explants from 18 day fetuses, dexamethasone inhibited both processes and reduced the level of stimulation of DSPC and fatty acid synthesis seen with aminophylline alone. Dexamethasone also reduced the stimulation of both DSPC and fatty acid synthesis produced in the culture of 18 day explants with bacitracin (0.5 mg/ml), whereas the combination of bacitracin and aminophylline resulted in a synergistic increase in DSPC production. Culture with glucagon (0.1 microM) also stimulated DSPC synthesis but at physiological levels insulin had no effect on either DSPC or fatty acid synthesis. These data show that lung fatty acid synthesis exhibits unique features of fatty acid synthesis regulation compared to other lipogenic tissues and also suggest a link between de novo fatty acid synthesis and surfactant production during the critical period of accelerated lung maturation.

Aminophylline↗
PubMed1986

Role of histamine in acute oleic acid-induced lung injury.

The action of histamine in oleic acid (OA)-induced injury was investigated using the isolated guinea pig lung perfused with blood-free media. OA infusion caused a significant increase in pulmonary arterial pressure, airway inspiratory pressure, lung weight, and protein flux across the alveolar-capillary barrier. These changes were dose dependent and caused injury regardless of the chemical form of OA (salt or free acid). Triolein (a neutral fat) infused at comparable emulsion particle size did not alter lung weight or bronchoalveolar lavage protein concentration in the perfused lung, suggesting that mechanical obstruction or emboli per se is not responsible for initiating early events in OA-induced injury. Infusion of OA caused a significant early histamine release into the venous effluent in the presence of aminoguanidine, a histamine catabolism inhibitor. Pretreatment with H1-receptor antagonists significantly attenuated OA-induced increase in lung weight and protein leak. These data support the link between OA-induced mast cell degranulation, histamine release, and OA-induced edema.

Animals↗
PubMed1986

Histamine action in paraquat-induced lung injury.

We investigated direct histamine release and its effects in edema formation following paraquat (PQ) injury in a blood-free, perfused rat lung preparation. Under control conditions, perfusate histamine levels from the lung averaged 9.5 +/- 1.4 ng/ml. Lungs perfused with paraquat (1 mM) showed marked increases in pulmonary arterial pressure (133%), airway pressure (74%), alveolarcapillary protein flux (200%), and lung weight (38%). Prior to any detectable lung weight or pressure changes, PQ caused a 300% increase in perfusate histamine. Diphenhydramine (1.0 X 10(-5) M), a specific H1-histamine receptor antagonist, blocked the increased protein flux that followed PQ administration and significantly delayed edema. Furthermore, diphenhydramine attenuated the rise in PGF2 alpha. Conversely, histamine release was partially attenuated by the cyclooxygenase inhibitor, ibuprofen, at 2.4 X 10(-5) M, the same level that we had previously shown to block an early rise in PGF2 alpha and the onset of edema after PQ. These data show that the increased alveolar-capillary protein flux that occurred with PQ injury was attenuated by an H1-receptor antagonist and suggest that histamine is a primary mediator in paraquat-induced injury and that histamine subsequently stimulates prostaglandin release.

Animals↗
PubMed1986

Integrated substrate utilization by perinatal lung.

The aims of this study were to examine the pattern and relative utilization of exogenously supplied substrates by the perinatal rat lung and to study their functional relationship at a key period of lung maturation (3 days before birth until one day after birth). Maximal incorporation of 14C-labeled substrates (glucose, lactate, glycerol, and beta-hydroxybutyrate) from the media into lung lipids occurred one day before birth and corresponded to maximal incorporation of 14C-choline into disaturated phosphatidylcholine (DSPC) (63 n moles X hr-1 X g-1), and to maximal increase in tissue DSPC concentration. Whereas, 14C-palmitate utilization for phospholipid synthesis was refractory to changes in DSPC synthesis. Lactate was shown to be a key substrate in fetal lung. When lactate and glucose were supplied at physiological concentrations, lactate: 1) provided 60% of the carbons for de novo fatty acid synthesis compared to only 9% from glucose, 2) produced 5 times more CO2 than glucose (23.9 vs. 4.9 u moles CO2 X hr-1 X g-1) and 3) altered the major fate of glucose incorporated into lung lipid from the fatty acid moiety to the glycerol moiety. Glycerol and palmitate were relatively unimportant energy fuels in the perinatal lung.

3-Hydroxybutyric Acid↗
PubMed1983

Selective action of prostaglandin F2 alpha during paraquat-induced pulmonary edema in the perfused lung.

Lung prostaglandins (PGs) play a key role in normal pulmonary vascular regulation. We investigated PG metabolism during edema formation following paraquat-induced damage with an isolated perfused rat lung preparation. Lungs perfused with paraquat (PQ), 1 X 10(-7) M to 1 X 10(-2) M, showed significant increases in PGF2 alpha prior to detectable functional and pathological changes (increases in airway resistance, vascular resistance, and edema). No changes in PGE were observed. PGF2 alpha in perfused lungs showed a dose-related response following PQ exposure (up to 300% increase over control values). Lungs perfused with PQ and ventilated with high oxygen (95% O2-5% CO2) instead of air-5% CO2 showed a dramatic potentiation in the selective increase of PGF2 alpha, with levels reaching over 1 ng/ml (a 2600% increase over control values). The addition of exogenous PGF2 alpha to the perfusate without PQ initiated edema in a dose-related fashion, indicating the potential of PGF2 alpha as a causative agent in lung edema formation from PQ injury. The addition of ibuprofen (a nonsteroidal anti-inflammatory agent) to the perfusion medium blocked endogenous release of PGF2 alpha in lungs linked to oxidant-induced edema. These data show that in the perfused lung: (1) PQ caused a selective increase of PGF2 alpha; (2) this selective increase occurred prior to the onset of edema; (3) exogenous PGF2 alpha alone induced pulmonary edema; and (4) ibuprofen, in doses which blocked PGF2 alpha, also prevented edema formation.

Animals↗
PubMed1979

Chronic intravenous infusion in the rat: a nonsurgical approach.

A rapid, simplified technique of intravenous catheterization of the unanesthetized rat was developed for continuous infusion. A 19-gauge thin-walled needle was inserted percutaneously into the dilated tail vein, and polyethylene tubing was advanced through the needle into the vein. The catheter was protected by wire mesh electrical sheathing taped securely to the tail. This approach eliminated the need for anesthesia and surgery which were traumatic to the animal and time consuming for the investigator. This method was used successfully in 32 rats given continous infusion for up to 5 days.

Animals↗
PubMedDate not supplied

Evidence for early signaling events in stomatin-induced differentiation of Tetrahymena vorax.

The mechanism of stomatin-induced differentiation of Tetrahymena vorax was investigated by in vivo protease degradation of cell surface proteins, the direct measurement of products formed from the activation of phospholipase C, and the use of an array of signal transduction inhibitors/activators. The data indicate that a surface-exposed protein is required for stomatin to signal the cells to differentiate and that the cells are committed to the differentiation pathway within two hours after exposure to stomatin. Analysis of radiolabeled polyphosphoinositols and inositol lipids from control and stomatin-treated populations in the presence of 10 mM LiCl were consistent with a rapid activation of phospholipase C. Within five min following addition of stomatin, this resulted in an increase in polyphosphoinositols and a concomitant decrease in the relative amounts of phosphatidylinositol bisphosphate and phosphatidylinositol trisphosphate.

Animals↗