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Biomedical subjects

J A Bos

Publications and source records attributed to J A Bos.

18 recordsLinked to original sources

Evaluation of lung function after intratracheal perfluorocarbon administration in healthy animals.

OBJECTIVES: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals. DESIGN: Prospective, randomized, controlled study. SETTING: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam. SUBJECTS: Ten adult male New Zealand rabbits. INTERVENTIONS: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters. MEASUREMENTS AND MAIN RESULTS: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins). CONCLUSIONS: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

Animals↗

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↗

A simple handheld push-button device for in situ calibration of pneumotachographs.

A simple and compact flow calibrator has been devised for generating precise predetermined constant flow rates for checking the calibration of laboratory and clinical flow transducers used in respiratory measurements. The standard version delivers preset flows of 0.5 and 1 l/s, whereas a tuned-up version can produce preset flows of 2.5 and 5 l/s, with an accuracy of +/- 2%. The pressure generated is sufficient to cope with most commonly used respiratory flowmeters. The flow calibrator is built from inexpensive components that are readily obtainable: a fan, a turbine flowmeter, and a feedback circuit in a compact housing. The device is easy to connect to other equipment and to operate. Three flow calibrators have been built and are in regular use in a lung function laboratory and on intensive care wards.

Calibration↗

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↗

Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.

BACKGROUND: The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA. METHODS: Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid. RESULTS: The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage. CONCLUSIONS: The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction.

Adult↗

Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content.

We measured clearance of 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of 99mTc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only.

Ambroxol↗

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↗

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↗

Online measurements of SaO2, Ht and Hb using a micro transmission cell.

Recently a Micro Transmission Cell has been developed based on spectrophotometry for in vivo monitoring of SaO2 together with Hb. A study in pigs was performed to compare the cell with standard methods for measuring SaO2, Hb and Ht. The results show that the cell is capable of following the trends of SaO2, Hb and Ht at different Hb concentrations and/or O2 saturations.

Animals↗

Pulmonary clearance of 99mTc-DTPA during halothane anaesthesia.

We studied the integrity of the alveolo-capillary barrier during different forms of anaesthesia by measuring the pulmonary clearance of inhaled 99mTc-DTPA. We studied four groups of rabbits. Groups I and II were anaesthetized with nembuthal only and the fractional concentration of inspired oxygen (F1O2) was 0.30 and 1.00, respectively. Groups III and IV were anaesthetized with 1% halothane and F1O2 was 0.30 and 0.99, respectively. 99mTc-DTPA was administered as a fine aerosol and the clearance of the tracer from the lungs was subsequently measured with a gamma camera. The mean half-life of the tracer in the lungs in Groups I-IV was 60, 58, 59 and 26 min, respectively. The rapid pulmonary clearance of 99mTc-DTPA in Group IV indicates that halothane in combination with high oxygen concentration increases the permeability of the alveolo-capillary barrier. This may be due to effects on the pulmonary surfactant system and/or the alveolar epithelium.

Anesthesia, Inhalation↗

Effects of high frequency jet ventilation on the pulmonary clearance of 99mTc-DTPA in respiratory failure in rabbits.

The effects of high frequency jet ventilation (HFJV) at 2 and 15 Hz on the pulmonary clearance of technetium 99m diethylene triamine pentaacetate (99mTc-DTPA) were compared with conventional volume-controlled (VC) ventilation with positive end-expiratory pressure (PEEP), in a model of respiratory failure induced by two lung lavages in adult rabbits. In group 1 the lungs were ventilated with HFJV at 2 Hz, and in group 2 ventilation was with HFJV at 15 Hz; group 3 underwent conventional VC ventilation. Group 4 also had conventional ventilation, but without previous lung lavage and functioned as a control group. In all groups, mean airway pressure was maintained at a value to ensure PaO2 greater than 25 kPa. The measured half-life time (T1/2) of the 99mTc-DTPA (mean (SD] was: group 1, 28 (7.8) min; group 2, 73.5 (7.9) min; group 3, 56.5 (12.4) min and group 4, 92.6 (13.2) min. Assuming that conventional VC with PEEP ventilation causes no additional harm to surfactant depleted lungs, it is concluded that HFJV at 2 Hz leads to further damage of the lungs, whereas HFJV at 15 Hz improves reparative processes, by keeping the lungs constantly inflated.

Anesthesia, Intravenous↗