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Biomedical subjects

G Enhorning

Publications and source records attributed to G Enhorning.

At least 37 records · Page 2Linked to original sources
PubMed1995

Pulmonary surfactant maintains patency of conducting airways in the rat.

The hypothesis was tested that after extrusion of the liquid columns that often block the lumen of conducting airways, the latter will remain open because of well-functioning pulmonary surfactant preventing the liquid columns from returning. The extirpated lungs of 22 Wistar rats were studied. Via a tracheal tube a very fine catheter (PE 10) was inserted and advanced until it pierced the pleura. It was extracted until only 2 mm remained in the lung parenchyma. A pressure transducer measured the resistance that met a steady flow of air through the series of tubes: the PE 10 tube, the conducting airway of the lung, and the tracheal tube. The airway resistance was studied for 240 s after three airway flushings, two with saline solution and one with calf lung surfactant extract (CLSE), 3 mg/ml. The pressure recording showed that a low pressure, indicating airway patency, occurred for only 31 +/- 8 s (mean +/- SEM) after the first saline flush, and for 26 +/- 8 s after the second. After the CLSE flush the airway remained open for 174 +/- 12 s, which indicated a significantly reduced resistance (p < 0.0001). The results imply that well-functioning pulmonary surfactant is required for a low airway resistance.

Airway Resistance↗
PubMed1993

Disruption of pulmonary surfactant's ability to maintain openness of a narrow tube.

Pulmonary surfactant stabilizes alveoli but, by maintaining patency of peripheral conducting airways, will also lower resistance to airflow. A small quantity of a surfactant suspension (3 mg/ml) formed a blocking liquid column in a narrow section of a glass capillary. Pressure was raised on one side of that column, whereby it was forced to move out of the narrow section, and it did not return but left the capillary open for a free airflow. The surfactant capability to maintain free airflow was lost with the addition of albumin (> 10 mg/ml) or fibrinogen (> 0.5 mg/ml). Surfactant function was seriously affected by hydrolysis with phospholipase C but not with phospholipase A2. With a small quantity of albumin added (5 mg/ml), the ability to maintain openness was seriously affected at temperatures below 25 degrees C. An inflammatory reaction due to atopy, infection, or inhalation of irritating gases characterizes a variety of airway diseases, including asthma. If the in vitro studies can be transferred to in vivo conditions, surfactant dysfunction might contribute to certain types of airway disease.

Animals↗
PubMed1993

Approximations in the measurement of surface tension on the oscillating bubble surfactometer.

This paper examines two factors, shape deformation and surface viscosity, that affect measurements of surface tension of lung surfactants with the oscillating bubble surfactometer. At lower surface tensions, the compressed bubble in this apparatus becomes deformed to an oblate ellipsoid that cannot be analyzed rigorously using the simplified (spherical) Laplace equation to calculate surface tension from interfacial pressure drop. However, for the small air bubbles present in this apparatus, analysis with more general equations for ellipsoids of revolution shows that deformation effects are limited to extremely low surface tensions, and the absolute error from the spherical approximation is minimal in practice. In contrast, this was not the case for the effects of surface dilational viscosity in oscillating bubble calculations. Direct measurements and values from the literature indicated that the surface dilational viscosities of lung surfactant, dipalmitoyl phosphatidylcholine, and palmitic acid were sufficient to give substantial errors if their effects on interfacial pressure drop were neglected during dynamic cycling. Surface tension calculations at maximum and minimum radii on the oscillating bubble apparatus remain accurate, because the time derivative of radius becomes zero and viscous effects vanish. However, surface tensions determined at points other than these extremes of bubble size should be interpreted with caution.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1993

Inhibition of fetal breathing: a pilot study.

Fetal breathing occurs sporadically and is inhibited during periods of hypoxemia, when blood, returning from the placenta, is mainly taking the shortcut through the ductus venosus. The hypothesis tested is that this inhibition might be caused by an expansion of the ductus venosus. Such expansion is pronounced during fetal life but ceases to occur after birth. Regular breathing of newborn lambs was recorded, and it was noted how the breathing was affected when blood, with the aid of a roller pump, was infused from the umbilical arteries into the umbilical veins. Nine lambs were examined, and for a maximal period of 2 min blood was infused into the umbilical veins at a rate of 50-150 mL/min. During 12 infusions, breathing temporarily came to a complete stop; in 30 cases, respiration was only partially inhibited; and in five cases, it was not affected. it is concluded that a very clear breathing inhibition may be obtained with an infusion of blood into the umbilical vein. It is speculated that expansion of the ductus venosus may trigger the inhibition and that the reason the effect varies may have to do with the fact that blood entering the body through the umbilical veins may predominantly take one of two routes: the ductus venosus or the hepatic vessels.

Animals↗
PubMed1992

Phospholipases introduced into the hypophase affect the surfactant film outlining a bubble.

The hypophase exchanger is a recently developed device that makes it possible to replace the liquid in the sample chamber of a pulsating bubble surfactometer, after a bubble has been formed, without changing the size of the bubble. A surfactant film outlining the bubble will retain its surface properties, provided the liquid entering the sample chamber and replacing the hypophase is inert. If, on the other hand, the new hypophase consists of a phospholipase solution, the physical properties of the film are seriously affected. It was found that when phospholipase C, even at low concentration, entered the sample chamber, the physical properties were significantly changed. Phospholipase A2 had to be added at a higher concentration to exert a similar effect. It is postulated that the site of action of phospholipase A2 may be partly protected in the hydrophobic region of the tightly packed surfactant film.

Animals↗
PubMed1991

Inhibition of pulmonary surfactant function by meconium.

The pathophysiology of meconium aspiration is marked by lung hyperinflation because of airway obstruction, which is often followed by an acute pneumonitis with classic lung injury characteristics. Surfactant dysfunction may contribute to this latter pulmonary pathophysiology. We sought to determine to what extent meconium itself might contribute to a functional surfactant deficiency. Specimens of newborn infants' first meconium were collected and pooled. Serial dilutions of the meconium were then added to various concentrations of calf lung surfactant extract, a mixture with the surface properties of natural surfactant that is used clinically to treat neonatal respiratory distress syndrome, and the dynamic surface activity of these mixtures was studied with a pulsating bubble surfactometer. At surfactant concentrations of less than or equal to 1.5 mg/ml, even 6500-fold dilutions of meconium-inhibited surface tension lowering ability (10 +/- 2 mN/m vs 1 +/- 0.1 mN/m for controls, p less than 0.05). Moreover, this inhibitory activity resided in both the chloroform-soluble and the aqueous phases of meconium and appeared to be additive in nature. However, at sufficiently high concentrations of surfactant, even large amounts of meconium were unable to affect surface tension lowering properties. Thus meconium inhibits surfactant function in a manner that is dependent on the surfactant concentration, suggesting the possible utility of exogenous surfactant therapy in some cases of meconium aspiration.

Animals↗
PubMed1991

Inhibition of pulmonary surfactant function by phospholipases.

Previous studies have shown that respiratory failure associated with disorders such as acute pancreatitis correlates well with increased levels of phospholipase A2 (PLA2) in lung lavages and that intratracheal administration of PLA2 generates an acute lung injury. In addition, bacteria such as Pseudomonas have been shown to secrete phospholipase C (PLC). We studied the effects of these phospholipases on pulmonary surfactant activity using a pulsating bubble surfactometer. Concentrations greater than or equal to 0.1 unit/ml PLA2 destroyed surfactant biophysical activity, increasing surface tension at minimum bubble size from less than 1 to 15 mN/m. This surfactant inactivation was predominantly related to the effect of lysophosphatidylcholine on the surface film, although the fatty acids released with higher PLA2 concentrations also had a detrimental effect on surfactant function. Similarly, as little as 0.1 unit PLC increased the surface tension at minimal size of an oscillating bubble from less than 1 to 15 mN/m, an effect that could be mimicked by the addition of dipalmitin to surfactant in the absence of PLC. Moreover, lower, noninhibitory concentrations (0.01 unit/ml) of PLA2 and PLC increased the sensitivity of surfactant to other inhibitory agents, such as albumin. Thus, relatively low concentrations of PLC and PLA2 can cause severe breakdown of surfactant function and may contribute significantly to some forms of lung injury.

Animals↗
PubMed1991

Pulmonary surfactant will secure free airflow through a narrow tube.

Well functioning pulmonary surfactant is necessary to ensure alveolar stability. It is proposed that surfactant is also required to keep the finest cylindrical airways open, thereby securing an unrestricted flow of air to and from the alveoli. If the surfactant is inadequate in quality or quality there is a risk that liquid will accumulate in the most marrow section of the airway and form a blocking column. To study that possibility special glass capillaries were used. The glass capillaries were heated and extended to make a short section very narrow. In the lumen of that section a minute volume (1 microliter) of liquid was deposited, which formed a blocking column. When pressure was raised on one side of the column, it forced the liquid to move away from the narrow section. Pressure dropped to zero as air could pass, and if the liquid column consisted of calf lung surfactant extract (CLSE), pressure remained at zero because a new liquid column did not form. If, on the other hand, the liquid column consisted of saline solution it would repeatedly reform as soon as it had been pressed out of the capillary's narrow section. The same occurred if the CLSE suspension forming the liquid column was very dilute or contained inhibiting proteins. These observations did not require that the capillary consisted of the material glass; they were also noted when the narrow tube was outlined by epithelium.

Air Pressure↗
PubMed1990

Biophysical inhibition of synthetic lung surfactants.

The biophysical activity and inhibition of a series of synthetic surfactant mixtures was studied and correlated with physiological effectiveness in restoring pressure-volume (P-V) mechanics of excised lungs. Results showed that several simple mixtures of dipalmitoyl phosphatidylcholine (DPPC) with fatty acids or diacylglycerols could be formulated to give good adsorption facility and dynamic surface tension lowering to less than 1 mN/m in pulsating bubble measurements at 37 degrees C. However, although biophysical activity approached that of natural lung surfactant (LS) and a related surfactant extract (CLSE) under normal conditions, surface properties were sharply inhibited by relatively small amounts of the plasma protein albumin (2 mg/ml) with minimum surface tensions greater than 30 nM/m even at high surfactant concentrations (5-20 mg lipids/ml). This sensitivity to biophysical inhibition was markedly increased compared to LS and CLSE, and had direct consequences for physiological efficacy: in spite of initially high activity, synthetic surfactants did not exert beneficial effects on P-V mechanics when instilled into surfactant-deficient excised rat lungs. Endogenous protein material was shown to be present upon surfactant recovery by lavage, and bubble measurements confirmed surface activity well below pre-instillation levels. Moreover, full biophysical activity was restored when lavage fluid was extracted to separate the synthetic surfactants from endogenous inhibitors. These results show that it is important to define relative sensitivity to biophysical inhibition in the development of effective lung surfactant substitutes. In addition, the existence of inhibition effects can generate an apparent lack of correspondence between initial biophysical activity and ultimate physiological actions of exogenous surfactant mixtures.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

A biophysical mechanism by which plasma proteins inhibit lung surfactant activity.

These in vitro experiments study a potential mechanism by which plasma proteins, found in the alveoli during pulmonary edema and hemorrhage, may act to inhibit the surface activity of pulmonary surfactant. The results indicate that the inhibition of the adsorption facility and surface tension lowering ability of a calf lung surfactant extract (CLSE) by albumin, hemoglobin, or fibrinogen may be completely abolished by centrifugation of the protein-surfactant mixture at 12,500 x g. Furthermore, albumin, hemoglobin and fibrinogen (1.25 mg/ml) were shown to inhibit the adsorption of high concentrations of CLSE (0.32 mg/ml), normally unaffected by the addition of exogenous proteins, when the CLSE was injected into the subphase under a preformed protein surface film. Similarly, injection of large amounts of these proteins (2.5 mg/ml) into the subphase beneath a preformed CLSE surface film was without effect, even though the CLSE concentration was only 0.06 mg/ml, a surfactant concentration which is normally inhibited by even small amounts of exogenous protein. Taken together, the data suggest that some proteins may inhibit surfactant function by preventing the surfactant phospholipids from adsorbing to the air-liquid interface, possibly by a competition between the proteins and CLSE phospholipids for space at the air-liquid interface rather than direct molecular interactions between proteins and surfactant.

Adsorption↗
PubMed1988

Maternal diabetes and its effect on biochemical and functional development of rabbit fetal lung.

The effect of maternal diabetes on functional and biochemical maturation of the fetal lung was studied in a rabbit model. Pregnancy was initiated only after diabetes had been established. Both the pregnant doe and its fetuses were hyperglycemic. For comparison, the fetal heart and liver were also studied. In the diabetic group, the DNA content was lower in the fetal heart and lung while the protein content was higher in all three tissues. The glycogen levels were higher only in the fetal lung. Glycogen synthase was higher in the fetal lung and heart while phosphorylase activity was higher in all three tissues from the diabetic group. The activities of key enzymes involved in glycolysis were not affected. No difference was observed in the concentration of total phospholipids or in the ability of the airway fluid to reduce surface tension. In contrast, fetal lungs from diabetic does did not expand as well as the controls and retained less air on deflation. These findings suggest that the utilization of glycogen in fetal lungs from the diabetic does was not complete and that the increased incidence of respiratory distress in infants of diabetic mothers may not be due to a lack of surfactant.

Animals↗
PubMed1988

Effect of reconstituted pulmonary surfactant containing the 6000-dalton hydrophobic protein on lung compliance of prematurely delivered rabbit fetuses.

Chloroform:methanol extracts of bovine pulmonary surfactant contain small hydrophobic proteins, designated surfactant-associated apoproteins 6,000 (SAP-6), but do not contain the major surfactant-associated 35,000-dalton glycoprotein, designated SAP-35. Examination of lipid extract surfactant on sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed hydrophobic proteins with apparent molecular masses of 15,000, 7,000, and 3,5000 daltons prior to reduction. After reduction, the 15,000-dalton species largely disappeared and was replaced by a 5,000-dalton species. In addition, the 7000- and 3500-dalton species exhibited a slightly enhanced mobility. Amino acid analysis demonstrated that SAP-6 possesses a more highly hydrophobic profile than SAP-35. Combining the protein-containing fractions from silicic acid chromatography of lipid extract with synthetic dipalmitoylphosphatidylcholine produced a reconstituted surfactant preparation which was just as active as lipid extract surfactant on a pulsating bubble surfactometer. The reconstituted surfactant contained SAP-6 but not SAP-35. Pressure-volume studies revealed that, at the optimal dose, reconstituted surfactant containing half the SAP-6 concentration of lipid extract exhibited similar effectiveness to lipid extract surfactant in promoting lung expansion with prematurely delivered rabbit fetuses of 27 days gestation. Reconstituted surfactant with an identical SAP-6 protein concentration as lipid extract possessed the same biological properties as the preparation with 1% SAP-6 protein. These studies support the view that an artificial surfactant composed of synthetic or semisynthetic lipids plus human SAP-6 produced via biotechnology could be useful for prevention and/or treatment of the neonatal respiratory distress syndrome.

Animals↗
PubMed1988

Two-year follow-up of infants enrolled in a randomized trial of surfactant replacement therapy for prevention of neonatal respiratory distress syndrome.

A randomized clinical trial of the use of bovine surfactant for the prevention of neonatal respiratory distress syndrome was completed at our Institution in 1984 (Pediatrics 1985;76:145-153). All infants entering the trial were enrolled in our follow-up clinic and seen at regular intervals for assessment of growth and development, neurologic and sensory status, and incidence of respiratory disease and allergic conditions. Infants have now been followed-up for at least 2 years. Of those infants for whom follow-up is complete, two of 32 (6.3%) surfactant-treated infants died, five (15.6%) had major neuro-developmental handicaps, and five had minor neurodevelopmental handicaps. In the control group, eight of 33 (24%) infants died, whereas only two (6.1%) survived with major neurodevelopmental handicaps, and four (12.1%) were left with minor handicaps. Except for an increased neonatal death rate in the control group, other differences were not statistically significant. The groups were also comparable in terms of the incidence of late respiratory or allergic disease as assessed by history. Treatment with bovine surfactant at birth of premature infants at high risk for respiratory distress syndrome appears to be safe and of short-term benefit, although no decrease in neurodevelopmental handicap at 2 years' follow-up can be demonstrated.

Clinical Trials as Topic↗
PubMed1987

Artificial pulmonary surfactant inhibited by proteins.

With a pulsating bubble surfactometer we assessed the ability of various agents, fibrinogen, human serum, albumin, and a 55,000-dalton serum protein, to interfere with the surface activity of Surfactant TA. From a highest final protein concentration of 4 mg/ml the potential inhibitors were diluted down to 0.125 mg/ml in six steps, and each concentration was evaluated together with two final phospholipid concentrations, 6.25 and 1.25 mg/ml, of the surfactant preparation. The strongest inhibiting action was exerted by fibrinogen, followed by human serum and the 55,000-dalton serum protein; the weakest inhibitor was albumin. Bilirubin, when added in an amount of 1.73 mg/100 ml dissolved in human serum, significantly (P less than 0.001) augmented the inhibition over that exerted by human serum alone. Adsorption rate, as reflected in the mean value of surface tension 2 and 10 s after creation of a bubble, not pulsating, was seriously affected by each of the protein-containing inhibitors in concentrations exceeding 1 mg/ml. Surface tension was raised significantly when the pulsating bubble was at maximal and minimal size. The effect was dose dependent. At maximal size it showed no tendency to disappear during the 10-min recording, but at minimal bubble size the inhibition gradually diminished. We conclude that proteins present in the airways may seriously interfere with the activity of Surfactant TA.

Blood Proteins↗
PubMed1987

Pathway of significance for the synthesis of pulmonary surfactant.

The most important component of pulmonary surfactant is dipalmitoyl phosphatidylcholine, or DPPC. At the end of an expiration, when the surfactant film is maximally compressed, DPPC is probably almost the sole component in the monomolecular film, but, during inspiration, as the film expands, other elements move in. They may be phospholipids with different fatty acids, saturated or unsaturated, or with the alcohol choline replaced with ethanolamine, inositol, glycerol or serine. The elements moving into the expanding film may also be free fatty acids, di- or triglycerides, etc. The synthesis of DPPC, similar to that of other phospholipids, has been thoroughly studied and is reviewed. The building blocks, glycerol, palmitic acid, choline and phosphate, are generally produced in the lung itself, but choline is generously supplied with the bloodstream. The slowest and, therefore, rate-limiting reaction is conversion of choline phosphate to cytidine diphosphate choline (CDP choline). The enzyme required, choline phosphate cytidyltransferase, is, therefore, crucial. It exists in two forms and can be stimulated to be converted to the more active H-form by the presence of phosphatidylglycerol. This would give PG a specific role; it has no unique ability to affect the surface tension, but it stimulates the synthesis of DPPC.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1987

Surfactant can be supplemented before the neonate needs it.

Pulmonary surfactant is a complex mixture, but clearly has one main component, dipalmitoylphosphatidylcholine, or DPPC. The respiratory distress syndrome, RDS, a condition afflicting the baby born too early, is caused by a deficiency of pulmonary surfactant. When this was first realized, attempts were made to treat the condition by supplying DPPC, the main component of the missing surfactant. These first attempts to supplement the pulmonary surfactant were unsuccessful, however, and with the bubble surfactometer, it is clearly seen that DPPC alone does not have the needed surface properties. The adsorption rate is too low, i.e., DPPC only is very slow in forming a film at the air-liquid interface. Natural surfactant on the other hand has the capacity to form a film instantaneously. Therefore, if natural surfactant is supplied in the upper airways prior to the first breath, it will immediately upgrade the maturity of the neonate's lungs; aeration is facilitated and the lungs are given stability. With a surfactant preparation, consisting of the lipids extracted from calf lung lavage, a randomized clinical trial was carried out on infants at particularly high risk of developing RDS. Of the 39 infants receiving surfactant prior to the first breath after birth, only one died neonatally; whereas, of the 33 controls, six died.

Animals↗