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Biomedical subjects

D Gommers

Publications and source records attributed to D Gommers.

At least 37 records · Page 2Linked to original sources
PubMed1998

Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats.

Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one group of rats, the time course of the development of lung injury due to paraquat intoxication was characterized. In a second group of rats, 72 h after paraquat intoxication, the animals underwent mechanical ventilation and only those animals in which the arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) decreased to below 20 kPa (150 mmHg) received exogenous surfactant (200 mg x kg(-1) body weight). Within 3 days the rats in group 1 developed progressive respiratory failure, demonstrated not only by impaired gas exchange and lung mechanics but also by increased minimal surface tension and increased protein concentration in bronchoalveolar lavage fluid. In group 2, intratracheal surfactant administration increased Pa,O2/FI,O2 significantly within 5 min (14.4+/-2.4 kPa (108+/-18 mmHg)) to (55.2+/-53 kPa (414+/-40 mmHg)) and sustained this level for at least 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of severe respiratory failure caused by paraquat poisoning.

Animals↗
PubMed1997

Improved oxygenation by nitric oxide is enhanced by prior lung reaeration with surfactant, rather than positive end-expiratory pressure, in lung-lavaged rabbits.

OBJECTIVES: The inhalation of nitric oxide increases oxygenation by improving the ventilation/perfusion ratios in neonates with respiratory distress syndrome and those ratios in adults with acute respiratory distress syndrome. There is evidence that inhaled nitric oxide is ineffective when the lung remains atelectatic and poorly inflated. This study aimed to enhance nitric oxide delivery by improving lung aeration by means of exogenous surfactant or by increasing positive end-expiratory pressure. DESIGN: Experimental, comparative study. SETTING: Research laboratory of a large university. SUBJECTS: Twenty-eight adult New Zealand white rabbits, weighing 2.7 +/- 0.3 kg. INTERVENTIONS: Lung injury was induced by repeated whole-lung lavage with saline. The animals were mechanically ventilated with a tidal volume of 10 mL/kg, an FIO2 of 1.0, and a positive end-expiratory pressure of 6 cm H2O. Forty-five minutes after the last lavage, the animals were randomly assigned to five groups. In two groups, lung aeration was first increased either by instillation of a low dose of exogenous surfactant (25 mg/kg) or by increasing the positive end-expiratory pressure to 10 cm H2O, before inhalation of nitric oxide was started. In each of these animals, five different nitric oxide concentrations (4 to 20 parts per million) were inhaled for 30 mins, followed by a 30-min washout period. The other three groups served as controls and received only one treatment protocol: nitric oxide (4 to 20 parts per million), or surfactant (25 mg/kg), or positive end-expiratory pressure (10 cm H2O). MEASUREMENTS AND MAIN RESULTS: Before and after lavage, blood gases and lung mechanics were measured every 30 mins. Both strategies to increase lung aeration improved PaO2 values from 61 +/- 13 torr (8.1 +/- 1.7 kPa) to 200 to 300 torr (26.6 to 39.9 kPa) in 30 mins. After inhalation of nitric oxide, additional increases of oxygenation were seen only in the animals that received a low dose (25 mg/kg) of surfactant. The control group that inhaled nitric oxide showed no significant change in oxygenation, and four of the six animals did not survive the observation period. In the two groups in which positive end-expiratory pressure was increased to 10 cm H2O, half of the animals developed a pneumothorax during the observation period. CONCLUSION: These data indicate that inhaled nitric oxide is able to improve arterial oxygenation after alveolar recruitment by means of a low dose of exogenous surfactant, and not by increase of positive end-expiratory pressure from 6 to 10 cm H2O, in lung-lavaged rabbits.

Administration, Inhalation↗
PubMed1996

Pulmonary 99mTc-human serum albumin clearance and effects of surfactant replacement after lung lavage in rabbits.

OBJECTIVE: Pulmonary clearance of technetium-labeled human serum albumin was measured in order to investigate whether the surfactant layer is a rate-limiting factor for the permeability of the alveolar-capillary membrane for 99mTc-labeled albumin. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Nineteen white New Zealand adult rabbits. INTERVENTIONS: Three groups of rabbits were studied: group 1 animals received natural surfactant after lung lavage; group 2 animals underwent lung lavage only; and group 3 animals were not lavaged and served as an untreated, healthy control group. All animals were ventilated with high pressures. MEASUREMENTS AND MAIN RESULTS: 99mTc-labeled albumin was nebulized into the inspiratory line of the breathing circuit with an air jet nebulizer. The clearance measurements were then immediately started. Gamma camera images were obtained in 1-min frames for 120 mins and stored in a 64 x 64 image matrix in a computer. In group 1 animals, surfactant restored blood gases to near normal, and all animals except one had bi-exponential clearance curves. The half-life of the fast compartment was 35.9 +/- 6.4 mins, and the half-life of the slow compartment was 847.5 +/- 143.5 mins. All group 2 animals also had bi-exponential clearance curves of the tracer (the half-lives of the fast and slow compartments were 14.6 +/- 6.7 and 459.8 +/- 167 mins, respectively). The half-lives of both the fast (p < .01) and slow (p < .01) components were significantly different between groups 1 and 2. Group 3 had a mono-exponential half-life of 580 +/- 225 mins. CONCLUSIONS: The use of 99mTc-human serum albumin as a tracer molecule is possible and feasible. The clearance of this tracer is, in part, determined by the integrity of the pulmonary surfactant system, as it is with 99mTc-diethylenetriamine pentaacetate.

Animals↗
PubMed1996

Exogenous pulmonary surfactant as a drug delivering agent: influence of antibiotics on surfactant activity.

1. It has been proposed to use exogenous pulmonary surfactant as a drug delivery system for antibiotics to the alveolar compartment of the lung. Little, however, is known about interactions between pulmonary surfactant and antimicrobial agents. This study investigated the activity of a bovine pulmonary surfactant after mixture with amphotericin B, amoxicillin, ceftazidime, pentamidine or tobramycin. 2. Surfactant (1 mg ml-1 in vitro and 40 mg ml-1 in vivo) was mixed with 0.375 mg ml-1 amphotericin B, 50 mg ml-1 amoxicillin, 37.5 mg ml-1 ceftazidime, 1 mg ml-1 pentamidine and 2.5 mg ml-1 tobramycin. Minimal surface tension of 50 microliters of the mixtures was measured in vitro by use of the Wilhelmy balance. In vivo surfactant activity was evaluated by its capacity to restore gas exchange in an established rat model for surfactant deficiency. 3. Surfactant deficiency was induced in ventilated rats by repeated lavage of the lung with warm saline until PaO2 dropped below 80 cmH2O with 100% inspired oxygen at standard ventilation settings. Subsequently an antibiotic-surfactant mixture, saline, air, or surfactant alone was instilled intratracheally (4 ml kg-1 volume, n = 6 per treatment) and blood gas values were measured 5, 30, 60, 90 and 120 min after instillation. 4. The results showed that minimal surface tensions of the mixtures were comparable to that of surfactant alone. In vivo PaO2 levels in the animals receiving ceftazidime-surfactant or pentamidine-surfactant were unchanged when compared to the surfactant group. PaO2 levels in animals receiving amphotericin B-surfactant, amoxicillin-surfactant or tobramycin-surfactant were significantly decreased compared to the surfactant group. For tobramycin it was further found that PaO2 levels were not affected when 0.2 M NaHCO3 (pH = 8.3) buffer was used for suspending surfactant instead of saline. 5. It is concluded that some antibiotics affect the in vivo activity of a bovine pulmonary surfactant. Therefore, before using surfactant-antibiotic mixtures in clinical trials, interactions between the two agents should be carefully evaluated.

Animals↗
PubMed1996

Pulmonary surfactant as vehicle for intratracheally instilled tobramycin in mice infected with Klebsiella pneumoniae.

1. The use of pulmonary surfactant has been proposed as a vehicle for antibiotic delivery to the alveolar compartment of the lung. This study investigated survival rates of mice with a respiratory Klebsiella pneumoniae infection treated intratracheally with tobramycin using a natural exogenous surfactant preparation as vehicle. 2. At day 1 after infection, animals were injected intratracheally with 20 microliters of the following solutions: (1) a mixture of surfactant (500 micrograms) and tobramycin (250 micrograms); (2) tobramycin (250 micrograms) alone; (3) surfactant (500 micrograms) alone; and (4) NaHCO3 buffer (control, sham-treatment). A fifth group received no treatment (control). Deaths were registered every 12 h for 8 consecutive days. 3. The results show an increased survival in the group receiving the surfactant-tobramycin mixture compared to the group receiving tobramycin alone (P < 0.05), the group receiving surfactant alone (P < 0.01) and the control groups (P < 0.01). It is concluded that intratracheal instillation of surfactant-tobramycin is superior to tobramycin alone in protecting animals from death due to a respiratory Klebsiella pneumoniae infection.

Animals↗
PubMed1995

Influence of pulmonary surfactant on in vitro bactericidal activities of amoxicillin, ceftazidime, and tobramycin.

The influence of a natural pulmonary surfactant on antibiotic activity was investigated to assess the possible use of exogenous surfactant as a vehicle for antibiotic delivery to the lung. The influence of surfactant on the bactericidal activity of amoxicillin was tested against Staphylococcus aureus and Streptococcus pneumoniae, and the influence of surfactant on the activities of ceftazidime and tobramycin was tested against Klebsiella pneumoniae, Pseudomonas aeruginosa, S. aureus, and S. pneumoniae. In vitro antibiotic activity was determined by killing curve studies in media with and without surfactant. Amoxicillin and ceftazidime activities were not changed in the presence of surfactant, except for a decreased killing rate of S. pneumoniae by ceftazidime in medium with additional rabbit serum. In contrast, killing curves with low concentrations of tobramycin (0.25x and 1x the MIC) showed a decreased level of activity of tobramycin against all pathogens tested in the presence of surfactant. With higher tobramycin concentrations (4x the MIC) killing rates were decreased less or were unchanged in the presence of surfactant. Concluding from the results of the study, both amoxicillin and ceftazidime can be combined with surfactant without the loss of activity. For mixing surfactant with tobramycin, dosages should be adjusted to overcome the partial inactivation of tobramycin by surfactant.

Amoxicillin↗
PubMed1995

Role of surfactant in the pathophysiology of the acute respiratory distress syndrome (ARDS).

Acute respiratory distress syndrome (ARDS) has become a well-recognized condition that can result from a number of different causes that lead to injury of the alveolar-capillary membrane. This results in high-permeability pulmonary oedema that disturbs the pulmonary surfactant system. In ARDS, the treatments available are still inadequate and morbidity, mortality, and costs remain unacceptably high. In the last 15 yrs, the morbidity and mortality rates of premature infants suffering from the respiratory distress syndrome (RDS) due to surfactant deficiency, have been reduced by exogenous surfactant therapy, and this treatment is now routinely used in most neonatal intensive care units. At this moment, only a few case reports and results of limited clinical pilot studies are available, in which patients with ARDS are treated with exogenous surfactant. Although the results from these studies are not consistent, the best results have been seen in patients treated with high concentrations or multiple doses of surfactant. It has been suggested that the increased permeability changes, along with the inflammatory response, lead to accumulation of plasma components in the alveolar space, causing inhibition of the instilled surfactant in a dose-dependent way. Thus, for treatment of ARDS, a high concentration of surfactant is required to overcome the inhibitory effect of plasma components. However, a few questions remain unanswered, including: When should surfactant treatment start? Which dosage? Of which type of surfactant? Which method of administration should be used, in combination with which type of ventilatory support, etc.?

Humans↗
PubMed1994

In vivo evaluation of the inhibitory capacity of human plasma on exogenous surfactant function.

OBJECTIVE: The adult respiratory distress syndrome (ARDS) and neonatal respiratory distress syndrome (RDS) are characterized by high permeability pulmonary edema which contains plasma-derived proteins inhibiting pulmonary surfactant function. Currently, discussion continues as to what dose of surfactant is required for treatment of these syndromes. DESIGN: The purpose of this study was to investigate the amount of exogenous surfactant needed to overcome the inhibitory components in human plasma. Male adult rats suffering from respiratory failure due to surfactant depletion after whole-lung lavage received human plasma (4 ml/kg body weight) mixed with surfactant at different concentrations, intratracheally. Rats receiving surfactant only at different concentrations served as controls. Blood gas analysis was performed. MEASUREMENTS AND RESULTS: It was demonstrated that plasma (4 ml/kg-273 mg plasma proteins/kg) mixed with surfactant at 300 mg/kg was able to increase and maintain PaO2 at normal values. Plasma mixed with surfactant at 100 mg/kg, after initial restoration of blood gases, showed deterioration of PaO2 values. Plasma mixed with surfactant at a dose of 50 mg/kg did not improve PaO2 whereas surfactant at 50 mg/kg, without plasma, restored blood gases to pre-lavage values. CONCLUSION: It is concluded that approximately 1 mg surfactant phospholipids is required to overcome the inhibitory effect of approximately 1 mg plasma proteins. For clinical practice this means that an excess of surfactant should be given, or repeatedly be substituted ("titrated") at low concentrations, until blood gases improve.

Animals↗
PubMed1993

Surfactant treatment of respiratory failure induced by hydrochloric acid aspiration in rats.

BACKGROUND: The surfactant system seems to be involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration. This study was an investigation of the effect of different treatment strategies using an exogenous surfactant preparation on lung function of rats suffering from respiratory failure after intratracheal HCl instillation. METHODS: In rats anesthetized with halothane, nitrous oxide, and oxygen, tracheotomy was performed and the lungs were mechanically ventilated. Respiratory failure was induced by intratracheal instillation of HCl (0.1 N, 3 ml/kg). After the PaO2 decreased to < 200 mmHg, the animals were randomly divided into five groups. Group I received no treatment; group II received a natural surfactant preparation intratracheally (200 mg/kg); group III underwent bronchoalveolar lavage (BAL) with saline, followed by surfactant treatment (200 mg/kg); and groups IV and V underwent BAL with saline and a diluted surfactant suspension (3.3 mg/ml in 30 ml/kg), respectively. Groups IV and V received a second and third BAL 60 and 120 min after the first lavage. Blood gas analysis and protein measurements in BAL fluids were performed. RESULTS: Gas exchange improved in Groups III and V only. Protein concentrations were high in all BAL fluids. In the rats receiving BAL three times (groups IV and V), a decrease in protein concentration was observed. CONCLUSIONS: From these results, it was concluded that plasma-derived proteins (which are known to inhibit surfactant function) are washed out of the alveoli by BAL, resulting in improved efficacy of surfactant treatment.

Animals↗
PubMed1993

Exogenous surfactant therapy increases static lung compliance, and cannot be assessed by measurements of dynamic compliance alone.

OBJECTIVE: To study the immediate effects of exogenous surfactant therapy on blood gases, lung volumes, and lung mechanics in adult rabbits with experimentally induced respiratory distress syndrome. DESIGN: Prospective randomized, controlled study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Twelve adult New Zealand white rabbits. INTERVENTIONS: Respiratory failure was induced by repeated bilateral whole-lung lavage with saline (30 mL/kg body weight). After the last lavage, the animals were randomly assigned to two groups. Group 1 received surfactant (120 mg/kg body weight) that was suspended in a 0.6% sodium chloride solution. Group 2 received comparable volumes of the same hypotonic solution and served as controls. MEASUREMENTS AND MAIN RESULTS: Before and after endotracheal surfactant instillation, blood gases and functional residual capacity were measured, and lung mechanics from tidal volumes and pressure-volume curves were calculated. Functional residual capacity was measured by a computerized, multiple-breath, washin-washout method using sulfur hexafluoride (SF6) as tracer gas. The pressure-volume curves were obtained by an occlusion technique originally described for measuring static breath-by-breath compliance. The technique was modified for present use and fully computerized. Within 60 mins after surfactant instillation, there were marked improvements in Pao2 (61 +/- 7 torr [8.2 +/- 0.9 kPa] to 470 +/- 47 torr [62.6 +/- 6.2 kPa]) and in functional residual capacity (7.6 +/- 1.4 to 17.7 +/- 1.6 mL/kg body weight) at unchanged ventilatory settings. The pressure-volume curves became steeper over time and the pressure-volume curves for total lung volume were restored to an almost normal state. Maximum compliance calculated from the pressure-volume curves increased by 92% but there was no significant change in dynamic compliance. In the control group, no improvements in any measured or calculated lung parameters were seen. CONCLUSIONS: The findings indicate that during mechanical ventilation, the effects of surfactant therapy on lung mechanics are best characterized by changes in functional residual capacity and maximum compliance obtained from static pressure-volume curves and not by dynamic compliance.

Animals↗
PubMed1993

Prevention of respiratory failure after hydrochloric acid aspiration by intratracheal surfactant instillation in rats.

Because the surfactant system probably is involved in the pathophysiology of respiratory failure caused by hydrochloric acid (HCl) aspiration, we investigated the effects of different ventilation strategies and intratracheal surfactant instillation at different time intervals on the course of pulmonary gas exchange after HCl aspiration in rats. In this study rats were anesthetized and mechanically ventilated via a tracheostomy. Respiratory failure was induced by intratracheal instillation of 3 mL/kg 0.1 N HCl. Animals (n = 49) were divided into nine groups: Groups 1 and 2 through 9 were ventilated with peak airway pressure/positive end-expiratory pressure of 14/2 and 26/6 cm H2O, respectively; Groups 3 and 4 received surfactant (200 mg/kg) intratracheally, 1 and 10 min after HCl aspiration; Groups 5 and 6 received saline, 1 and 10 min after HCl aspiration; Groups 7 and 8 received surfactant, 60 and 90 min after HCl aspiration; Group 9 received saline instead of HCl. Gas exchange deteriorated in Groups 1, 2, 5, 6, 7, and 8, whereas respiratory failure could be prevented in Groups 3 and 4. After deterioration of gas exchange, surfactant treatment prevented further decrease of PaO2 values in Group 7, whereas no effect on gas exchange was observed in Group 8; intratracheal instillation of saline had no effect on gas exchange (Group 9). These results suggest that surfactant should be given as early as possible after aspiration of gastric contents to prevent development of respiratory failure.

Animals↗
PubMed1992

Surfactant replacement therapy improves pulmonary mechanics in end-stage influenza A pneumonia in mice.

Surfactant replacement therapy may be a promising approach for treatment of respiratory failure caused by viral pneumonia. This study in mice demonstrates that during the development of lethal influenza A pneumonia, thorax-lung compliance (Ctl/kg) and lung volume at 5 cm H2O PEEP (V5/kg) significantly decrease (28 and 54%, respectively), whereas lung water content significantly increases (25%). Surfactant replacement therapy during the end stage of pneumonia significantly increases Ctl/kg (31%) and V5/kg (21%). Instillation of the vehicle for surfactant in control animals does not significantly affect Ctl/kg (5% decrease), but it significantly decreases V5/kg (25% decrease). Further, a new method for postmortem measurement of lung volumes in small laboratory animals based on Archimedes' principle is presented.

Animals↗
PubMed1992

Natural surfactant instilled in premature lambs increases lung volume and improves ventilation homogeneity within five minutes.

The immediate effects on lung volume, ventilation homogeneity, and lung mechanics of tracheal instillation of surfactant were studied in premature lambs, gestational age 120-122 d, with respiratory distress syndrome. Six lambs received surfactant by tracheal instillation 25 min after delivery by cesarean section; five received only vehicle and served as controls. The lambs were studied for 60 min thereafter. Functional residual capacity was measured with a computerized tracer gas washin-washout technique using sulfur hexafluoride as tracer gas. A measure of ventilation inhomogeneity (pulmonary clearance delay) was also calculated from the washout curves. Pressure-volume curves were studied with an interrupter technique during deflation of the lungs from an airway pressure of 30 cm H2O. In the surfactant group, arterial oxygenation and ventilation homogeneity improved within 5 min of giving surfactant; major increases in functional residual capacity, vital capacity, and compliance occurred within 5 to 20 min and were followed by gradual further improvements. The pressure-volume curve thus increased in amplitude and became steeper, but the lung volumes at various inflation pressures, and compliance, remained constant when expressed as fractions of total lung capacity volume. It is concluded that an improvement in lung volume, respiratory mechanics, and ventilation homogeneity occurs very soon after surfactant instillation and that there is a phase of successive further improvement over the next hour. Although the amplitude of the pressure-volume curve varied considerably, its basic shape varied little. This suggests that opening of new distal airways by surfactant predominated over changes in the mechanics of already aerated lung regions.

Animals↗