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Biomedical subjects

G Enhorning

Publications and source records attributed to G Enhorning.

At least 19 recordsLinked to original sources
PubMed1998

Ozone affects breathing and pulmonary surfactant function in mice.

The effect on breathing of BALB/c mice immediately following ozone exposure (2 ppm) for 0, 2, 4, 6, and 8 h was studied with a whole body plethysmograph. Whether such exposure affected the normal function of pulmonary surfactant of maintaining airway patency was evaluated with a capillary surfactometer. Respiratory rate in mice that were not exposed was 358+/-16 (mean+/-S.E.) breaths/min and decreased to 202+/-10 after 6 h exposure. The mean pressure change caused by breathing diminished significantly, indicating a reduced tidal volume. BAL fluid from controls maintained patency for 88+/-2% of the study time, 120 s, implying a good surfactant function, but the ozone exposure caused the surfactant to lose its capability of maintaining patency (P < 0.0001). This decaying surfactant function of the BAL fluid coincided with an increasing protein concentration in the fluid of exposed animals (1.46+/-0.14 mg/ml in the 8-h group) as compared to controls (0.44+/-0.04 mg/ml, P < 0.0001). It is concluded that leakage of plasma proteins into the airway lumen was probably the main reason for the surfactant dysfunction, which may have contributed to the altered breathing pattern.

Animals↗
PubMed1998

Respiratory syncytial virus affects pulmonary function in BALB/c mice.

BALB/c mice inoculated intranasally with respiratory syncytial virus (RSV) were studied in a whole-body plethysmograph to determine if signs of respiratory illness similar to those observed in human infants could be detected. Also, responsiveness to methacholine was assessed. RSV-infected mice showed significantly higher respiratory rates than did controls (409.2 vs. 305.2 breaths/min, P < .0001). Significantly increased airway responsiveness to methacholine was noted, infected mice responding to a 100-fold lower dose than controls (P = .003). Together, these data provide the first objective evidence of respiratory illness in the mouse model of RSV infection, which enhances the value of this model for evaluating effects of vaccines, antivirals, and other drugs acting on respiratory tract disease caused by RSV.

Animals↗
PubMed1998

Breathing and pulmonary surfactant function in mice 24 h after ozone exposure.

The aim of this study was to determine whether an acute ozone exposure affects breathing, and the ability of pulmonary surfactant to maintain the patency of terminal conducting airways. BALB/c mice were exposed to ozone (1 part per million (ppm)) for 2, 4, 6, and 8 h. They were examined with plethysmography and with bronchoalveolar lavage (BAL) 24 h later. The BAL fluid was analysed for the presence of inflammatory cells and concentrations of proteins and phospholipids. Surfactant in the remaining BAL fluid was concentrated five-times and examined with a capillary surfactometer (CS). The surfactant was then washed with a large volume of saline solution which was removed following centrifugation. Already, after a 2 h ozone exposure, the respiratory frequency increased from 297+/-6 to 386+/-11 breaths x min(-1) (p<0.0001). Pressure amplitude per breath diminished (p<0.001), indicating a reduced tidal volume. A highly significant surfactant dysfunction was observed with the CS (p<0.0001), although phospholipids increased. However, proteins also increased (p<0.0001) and they or other water-soluble inhibitors apparently caused the surfactant dysfunction since, when they were removed with a washing procedure, the surfactant's normal ability to maintain patency was restored. The acute ozone exposure affected breathing and caused an airway inflammation. The inflammatory proteins or other water-soluble inhibitors reduced the surfactant's ability to secure airway patency.

Animals↗
PubMed1997

Surface properties after a simulated PLA2 hydrolysis of pulmonary surfactant's main component, DPPC.

The inflammation, so conspicuous in cases of respiratory distress, pneumonia, and asthma, is associated with an airway invasion of plasma proteins and a release into the airway lumen of phospholipase A2 (PLA2). This enzyme catalyzes hydrolysis of surfactant phospholipids, the most abundant and important of which is dipalmitoylphosphatidylcholine (DPPC). Its hydrolysis yields equimolar proportions of lysophosphatidylcholine and palmitic acid (LPC/PA). Exact quantification of DPPC hydrolysis is complicated. Consequently, it was decided to simulate hydrolysis whereby DPPC (3 mg/ml) was gradually replaced with LPC/PA (3 mg/ml), yielding seven different grades of simulated hydrolysis: 0, 17, 33, 50, 67, 83, and 100%. Surface properties of the seven mixtures were examined with various concentrations of albumin added. The Bubble Surfactometer was used to study the surfactant film that is given time to develop at a spherical air-liquid interface. A Capillary Surfactometer was used to evaluate surface properties required for airway patency. It was found, using both of these instruments that the surface activity improved as the simulated hydrolysis of DPPC to LPC/PA increased toward 100%, where the activity was maximal. With the Bubble Surfactometer, surface activity of LPC/PA, 3 mg/ml, improved as albumin concentration increased, and when it reached 15 mg/ml, surface tension became 0 mN/m after only 2 min. With the Capillary Surfactometer, requiring a much faster film adsorption, albumin had an opposite effect. LPC/PA alone maintained patency 100% of the time studied, while even a minimal addition of albumin inhibited surfactant function.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Dysfunction of guinea-pig pulmonary surfactant and type II pneumocytes after repetitive challenge with aerosolized ovalbumin.

BACKGROUND: Asthma symptoms may partially be caused by a surfactant dysfunction. The inflammatory reaction, so characteristic of asthma, involves a protein invasion of airways which harmfully affects the surfactant function. However, mild asthma attacks might also impede the surfactant synthesis in alveolar type II cells. OBJECTIVE: The present study evaluates the hypothesis that type II pneumocyte metabolic function might be disturbed in a model of mild asthma. METHODS: Immunized, as well as not immunized control guinea-pigs, were challenged three times at two-day intervals with 0.04% ovalbumin aerosol. Bronchoalveolar lavage (BAL) was performed one day after the last challenge and the fluid was evaluated for surface activity, and content of phospholipids and proteins. Alveolar type II cells were isolated and their ability to incorporate a 3H labeled surfactant precursor was evaluated. RESULTS: BAL fluid from immunized and challenged animals showed less surface activity (P < 0.01) when compared with BAL fluid from controls, not immunized but challenged. Most likely the reduced surface activity was caused by a 74% increase in the protein concentration (P < 0.05). Isolated type II cells from immunized and challenged animals had 33% less phospholipids than cells from controls (P < 0.05), and phosphatidylcholine synthesis was reduced 35% (P < 0.05). CONCLUSION: These results suggest that the synthesis, intra-cellular storage, and biophysical activity of surfactant are decreased in an intermittent and mild form of asthma.

Allergens↗
PubMed1997

Surfactant dysfunction develops in BALB/c mice infected with respiratory syncytial virus.

Recent reports suggest an important role for pulmonary surfactant in maintaining the patency of narrow conducting airways. The hypothesis that surfactant dysfunction is an important factor in respiratory syncytial virus (RSV) infection was tested in a mouse model. Mice, inoculated with either a low or a high dose of RSV, were subjected to bronchoalveolar lavage (BAL), and the fluids were analyzed for percentage of inflammatory cells and concentrations of proteins and phospholipids. After concentration of the surfactant by centrifugation, its function was analyzed with a capillary surfactometer. RSV infection resulted in a dose-dependent disruption of surfactant function (p < 0.0001). BAL fluid supernatants were added to calf lung surfactant extract (CLSE) to examine whether surfactant inhibiting agents were present. Indeed, BAL fluid supernatants of RSV-infected mice disrupted the normal function of calf lung surfactant extract in a dose dependent way (p < 0.0001), indicating the presence of inhibitors. Protein concentrations were increased in BAL fluids of RSV-infected mice versus control mice (p < 0.0001), and were inversely related to surfactant function (r = -0.44, p = 0.0004), suggesting an inhibitory effect of proteins. Protein concentration also correlated with the percentage of inflammatory cells (r = 0.51, p = 0.004). Phospholipid concentrations were not affected by the RSV infection. The results of these studies strongly suggest that a disruption of pulmonary surfactant function, most likely due to inhibition from inflammatory proteins, is important for the pathophysiology of RSV infection.

Animals↗
PubMed1996

Pulmonary surfactant given prophylactically alleviates an asthma attack in guinea-pigs.

BACKGROUND: Previous studies have indicated that the increased airway resistance that develops in asthma may partly be due to a surfactant dysfunction. If so, it might be possible to alleviate the acute signs following an allergen challenge by prophylactically instilling into the airways a well functioning pulmonary surfactant. OBJECTIVE: The study was planned and enacted to test the above hypothesis. METHODS: The lung function (airway resistance, tidal volume, minute ventilation, and dynamic compliance) of 22 immunized guinea-pigs was studied for 30 min following a challenge. Ten of the animals had received a tracheal instillation of 0.5 mL calf lung surfactant extract (CLSE, 35 mg/mL) prior to the challenge. RESULTS: The animals receiving the dose of 17.5 mg surfactant were less affected by the challenge than were the controls. Only one of them died following the challenge, whereas four of the 12 controls succumbed. Lung function was significantly less affected among the nine surviving animals treated with surfactant prior to the challenge than among the eight surviving controls (P < 0.01) and also their blood gases (pCO2 and pO2) were less influenced (P < 0.05). CONCLUSION: The study indicated that the symptoms developing after a challenge, which to some extent simulate those of asthma, can be alleviated by a prophylactic airway instillation of pulmonary surfactant.

Animals↗
PubMed1996

Increased airway resistance due to surfactant dysfunction can be alleviated with aerosol surfactant.

To investigate the contribution of pulmonary surfactant to a low airflow resistance through narrow conducting airways, a system was developed with which it was possible to determine the resistance meeting a steady flow of air at 0.5 mL/min. The airflow, delivered by an infusion pump, entered the extreme periphery of a conducting airway in an excised rat lung and exited through the trachea. The resistance was determined by measuring the pressure of the air entering the lung. If the airway remained open, the pressure was only slightly above zero; when a blocking liquid column formed in the lumen of the airway, the pressure increased rapidly but dropped abruptly as the liquid was pushed away into a wider airway section. When endogenous pulmonary surfactant was removed with a saline lavage, the airway was blocked almost constantly by an endless re-formation of liquid columns. Consequently, during a 4-min period of pressure recording, free airflow was observed only rarely. However, administration of aerosol surfactant increased the duration of free airflow in relation to the volume administered. After an injection of 80 mL of aerosol surfactant, the airway stayed open 89 +/- 3% of the 4-min recording time compared with only 28 +/- 5% when the same volume of air (80 mL) without surfactant had passed through the airway (p < 0.0001). We conclude that surfactant contributes to a free airflow through conducting airways and may have an important role in the maintenance of low airway resistance.

Aerosols↗
PubMed1995

Surfactant dysfunction develops when the immunized guinea-pig is challenged with ovalbumin aerosol.

BACKGROUND: The cause of the airway resistance developing during an asthma attack is not completely understood. Besides bronchospasm and airway oedema a surfactant dysfunction has been suggested as a reason for an increased airway resistance. OBJECTIVE: This paper aims at examining if indeed surfactant dysfunction develops when an asthma attack is induced in guinea-pigs. METHODS: Guinea-pigs, immunized against ovalbumin and then challenged (by inhaling the antigen) underwent lung function tests (n = 7) and were compared with seven animals challenged, but not immunized. Lung lavage was carried out in three groups of guinea-pigs: controls, never immunized nor challenged (n = 7), not immunized but challenged (n = 6), immunized and challenged, no lung function test (n = 6). After concentrating the lavage fluid 10 times the surface activity was evaluated with the pulsating bubble surfactometer. The fluid's concentration of phospholipids and proteins was determined as was the phospholipid composition. RESULTS: The 19 immunized and challenged animals all developed severe respiratory distress, six so seriously that they died. Lung function tests showed significantly increased airway resistance and decreased tidal volume, minute volume, and dynamic compliance. Surface activity of lavage fluid from immunized and challenged animals was significantly reduced when compared with fluid from control animals (P < 0.01). Immunization and challenge had no effect on the lavage fluid's phospholipid concentration or composition, but the proteins were at a higher concentration than in the fluid of the controls (P < 0.01). CONCLUSION: Proteins leaking into the airways inhibited the surfactant. This, in turn might have caused conducting airways to become blocked by liquid columns, which would increase airway resistance.

Administration, Inhalation↗
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↗