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S J Verbrugge

Publications and source records attributed to S J Verbrugge.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of ventilation-induced lung injury with exogenous surfactant.

OBJECTIVE: It has been demonstrated that pulmonary surfactant plays a role in the pathophysiology of ventilation-induced lung injury (VILI). Therefore, we investigated whether exogenous surfactant might restore lung function and lung mechanics in an established model of VILI. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: Twenty-four adult male Sprague-Dawley rats. INTERVENTIONS: First, a group of six animals were killed immediately after induction of anesthesia and used as healthy controls. Then, in 18 rats, VILI was induced by increasing peak inspiratory pressure (PIP) to 45 cmH2O without positive end-expiratory pressure (PEEP) for 20 min. Thereafter, animals were randomly divided into three groups of six animals each: one group was killed immediately after VILI and served as VILI-control. In the other two groups, ventilator settings were changed to a PIP of 30 cmH2O and a PEEP of 10 cmH2O, and a respiratory rate of 40 bpm. One group received a bolus of surfactant and the other group received no treatment. MEASUREMENTS AND RESULTS: Blood gas tension and arterial blood pressures were recorded every 30 min for 2 h. After the study period, a pressure-volume curve was recorded. Then, a broncho-alveolar lavage (BAL) was performed to determine protein content, minimal surface tension, and surfactant composition in the BAL fluid. Oxygenation, lung mechanics, surfactant function and composition were significantly improved in the surfactant-treated group compared to the ventilated and non-ventilated control groups. CONCLUSION: We conclude that exogenous surfactant can be used to treat VILI.

Animals↗
PubMed2001

Partial liquid ventilation improves lung function in ventilation-induced lung injury.

Disturbances in lung function and lung mechanics are present after ventilation with high peak inspiratory pressures (PIP) and low levels of positive end-expiratory pressure (PEEP). Therefore, the authors investigated whether partial liquid ventilation can re-establish lung function after ventilation-induced lung injury. Adult rats were exposed to high PIP without PEEP for 20 min. Thereafter, the animals were randomly divided into five groups. The first group was killed immediately after randomization and used as an untreated control. The second group received only sham treatment and ventilation, and three groups received treatment with perfluorocarbon (10 mL x kg(-1), 20 mL x kg(-1), and 20 ml x kg(-1) plus an additional 5 mL x kg(-1) after 1 h). The four groups were maintained on mechanical ventilation for a further 2-h observation period. Blood gases, lung mechanics, total protein concentration, minimal surface tension, and small/large surfactant aggregates ratio were determined. The results show that in ventilation-induced lung injury, partial liquid ventilation with different amounts of perflubron improves gas exchange and pulmonary function, when compared to a group of animals treated with standard respiratory care. These effects have been observed despite the presence of a high intra-alveolar protein concentration, especially in those groups treated with 10 and 20 mL of perflubron. The data suggest that replacement of perfluorocarbon, lost over time, is crucial to maintain the constant effects of partial liquid ventilation.

Animals↗
PubMed2000

Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-alpha.

OBJECTIVES: To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-alpha response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP). DESIGN AND SETTING: Prospective, randomized, animal study in an experimental laboratory of a university. SUBJECTS AND INTERVENTIONS: 85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-alpha production; control animals received a similar amount of saline. Animals were subsequently ventilated for 20 min in a pressure control mode with peak inspiratory pressure/PEEP ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO2 = 1). MEASUREMENTS AND RESULTS: Blood gas tension and arterial pressures were recorded at 1, 10, and 20 min after start of mechanical ventilation. After killing of the animals pressure-volume curves were recorded, and bronchoalveolar lavage (BAL) was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and BAL. TNF-alpha levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-alpha to the nonstimulated compartment as opposed to ventilation with a PEEP level of 10 cmH2O. CONCLUSIONS: Ventilation strategies which are known to induce ventilation-induced lung injury (VILI) disturb the compartmentalization of the early cytokines response in the lung and systemically. Furthermore, the loss of compartmentalization is a two-way disturbance, with cytokines shifting from the vascular side to the alveolar side and vice versa. A ventilation strategy (PEEP level of 10 cmH2O) which prevents VILI significantly diminished this shift in cytokines.

Analysis of Variance↗
PubMed2000

Mechanical ventilation with high positive end-expiratory pressure and small driving pressure amplitude is as effective as high-frequency oscillatory ventilation to preserve the function of exogenous surfactant in lung-lavaged rats.

OBJECTIVE: To demonstrate that under well-defined conditions, pressure-controlled ventilators (PCV) allow settings that are as good as high-frequency oscillatory ventilators (HFOV) at preserving the function of exogenous surfactant in lung-lavaged rats. DESIGN: Experimental, comparative study. SETTING: Research laboratory of a large university. SUBJECTS: Sixteen adult male Sprague-Dawley rats (280-310 g). INTERVENTIONS: Lung injury was induced by repeated lavage. After last lavage, all animals received exogenous surfactant and were then randomly assigned to two groups (n = 8 per group). The first group received PCV with small pressure amplitudes and high positive end-expiratory pressure. The second group received HFOV. In both groups, an opening maneuver was performed by increasing airway pressure to improve PaO2/F(IO2) to > or =500 torr. MEASUREMENTS AND MAIN RESULTS: Blood gases were measured every 30 mins for 3 hrs. Airway pressures were measured with a tip catheter pressure transducer. At the end of the study period, a pressure-volume curve was recorded and a broncho-alveolar lavage was performed to determine protein content and surfactant composition. The results showed that arterial oxygenation in both groups could be kept >500 torr during the 3-hr study period by using a mean airway pressure of 13+/-3 cm H2O in PCV and 13+/-2 cm H2O in HFOV. Further, there were no differences in the Gruenwald index, protein influx, or ratio of small to large aggregates between the study groups. CONCLUSION: PCV with sufficient level of positive end-expiratory pressure and small driving pressure amplitudes is as effective as HFOV to maintain optimal gas exchange, to improve lung mechanics, and to prevent protein influx and conversion of large into small aggregates after exogenous surfactant therapy in lung-lavaged rats.

Animals↗
PubMed1999

The open lung concept: pressure-controlled ventilation is as effective as high-frequency oscillatory ventilation in improving gas exchange and lung mechanics in surfactant-deficient animals.

OBJECTIVE: To demonstrate in experimental animals with respiratory insufficiency that under well-defined conditions, commercially available ventilators allow settings which are as effective as high-frequency oscillatory ventilators (HFOV), with respect to the levels of gas exchange, protein infiltration, and lung stability. DESIGN: Prospective, randomized, animal study. SETTING: Experimental laboratory of a university. SUBJECTS: 18 adult male Sprague-Dawley rats. INTERVENTIONS: Lung injury was induced by repeated whole-lung lavage. Thereafter, the animals were assigned to pressure-controlled ventilation (PCV) plus The Open Lung Concept (OLC) or HFOV plus OLC (HFO(OLC)). In both groups, an opening maneuver was performed by increasing airway pressures to improve the arterial oxygen tension/fractional inspired oxygen (PaO(2)/FIO(2)) ratio to L 500 mm Hg; thereafter, airway pressures were reduced to minimal values, which kept PaO(2)/FIO(2) L 500 mm Hg. Pressure amplitude was adjusted to keep CO(2) as close as possible in the normal range. MEASUREMENTS AND RESULTS: Airway pressure, blood gas tension, and arterial blood pressure were recorded every 30 min. At the end of the 3-h study period, a pressure-volume curve was recorded and bronchoalveolar lavage was performed to determine protein content. After the recruitment maneuver, the resulting mean airway pressure to keep a PaO(2)/FIO(2) L 500 mm Hg was 25 +/- 1.3 cm H(2)O during PCV(OLC) and 25 +/- 0.5 cm H(2)O during HFOV(OLC). Arterial oxygenation in both groups was above L 500 mm Hg and arterial carbon dioxide tension was kept close to the normal range. No differences in mean arterial pressure, lung mechanics and protein influx were found between the two groups. CONCLUSIONS: This study shows that in surfactant-deficient animals, PCV, in combination with a recruitment maneuver, opens atelectatic lung areas and keeps them open as effectively as HFOV.

Animals↗
PubMed1999

Lung clearance of intratracheally instilled 99mTc-tobramycin using pulmonary surfactant as vehicle.

1. The use of pulmonary exogenous surfactant as a vehicle for intratracheally administered antibiotics to improve local antimicrobial therapy has been proposed. The present study investigated lung clearance rates in the rat of intratracheally instilled technetium labelled tobramycin with and without the addition of surfactant to the antibiotic solution. 2. The influence of surfactant on 99mTc-tobramycin lung clearance rates was studied dynamically with a gamma-camera in anaesthetized spontaneously breathing animals and in mechanically ventilated animals. 3. The results show that instillation of 99mTc-tobramycin with use of surfactant as vehicle significantly increases 99mTc-tobramycin lung clearance compared to instillation of 99mTc-tobramycin solution alone (P=0.006 between the two spontaneously breathing groups of animals and P=0.02 between the two ventilated groups of animals, ANOVA for repeated time measurements). The half life (t1/2) of composite clearance curves in spontaneous breathing animals was 147 min for animals receiving 99mTc-tobramycin versus 61 min for animals receiving 99mTc-tobramycin with surfactant. In mechanically ventilated animals this was 163 min versus 51 min, respectively. 4. It is concluded that exogenous surfactant, used as vehicle for intratracheally instilled 99mTc-tobramycin, increases lung clearance rate of 99mTc-tobramycin in rats.

Administration, Inhalation↗
PubMed1999

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury.

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.

Animals↗
PubMed1999

Different ventilation strategies affect lung function but do not increase tumor necrosis factor-alpha and prostacyclin production in lavaged rat lungs in vivo.

BACKGROUND: Using an in vivo animal model of surfactant deficiency, the authors compared the effect of different ventilation strategies on oxygenation and inflammatory mediator release from the lung parenchyma. METHODS: In adult rats that were mechanically ventilated with 100% oxygen, acute lung injury was induced by repeated lung lavage to obtain an arterial oxygen partial pressure < 85 mmHg (peak pressure/positive end-expiratory pressure [PEEP] = 26/6 cm H2O). Animals were then randomly assigned to receive either exogenous surfactant therapy, partial liquid ventilation, ventilation with high PEEP (16 cm H2O), ventilation with low PEEP (8 cm H2O), or ventilation with an increase in peak inspiratory pressure (to 32 cm H2O; PEEP = 6 cm H2O). Two groups of healthy nonlavaged rats were ventilated at a peak pressure/PEEP of 32/6 and 32/0 cm H2O, respectively. Blood gases were measured. Prostacyclin (PGI2) and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum and bronchoalveolar lavage fluid (BALF) as well as protein concentration in BALF were determined after 90 and 240 min and compared with mechanically ventilated and spontaneously breathing controls. RESULTS: Surfactant, partial liquid ventilation, and high PEEP improved oxygenation and reduced BALF protein levels. Ventilation with high PEEP at high mean airway pressure levels increased BALF PGI2 levels, whereas there was no difference in BALF TNF-alpha levels between groups. Serum PGI2 and TNF-alpha levels did not increase as a result of mechanical ventilation when compared with those of spontaneously breathing controls. CONCLUSIONS: Although alveolar protein concentration and oxygenation markedly differed with different ventilation strategies in this model of acute lung injury, there were no indications of ventilation-induced systemic PGI2 and TNF-alpha release, nor of pulmonary TNF-alpha release. Mechanical ventilation at high mean airway pressure levels increased PGI2 levels in the bronchoalveolar lavage-accessible space.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Purine in bronchoalveolar lavage fluid as a marker of ventilation-induced lung injury.

OBJECTIVE: To investigate in a rat model of ventilation-induced lung injury whether metabolic changes in the lung are reflected by an increased purine concentration (adenosine, inosine, hypoxanthine, xanthine, and urate; an index of adenosine-triphosphate breakdown) of the bronchoalveolar lavage fluid and whether purine can, thus, indirectly serve as a marker of ventilation-induced lung injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Research laboratory. SUBJECTS: Forty-two male Sprague-Dawley rats. INTERVENTIONS: Five groups of Sprague-Dawley rats were subjected to 6 mins of mechanical ventilation. One group was ventilated at a peak inspiratory pressure of 7 cm H2O and a positive end-expiratory pressure of 0 cm H2O. A second group was ventilated at a peak inspiratory pressure of 45 cm H2O and a positive end-expiratory pressure of 10 cm H2O. Three groups of Sprague-Dawley rats were ventilated at a peak inspiratory pressure of 45 cm H2O without positive end-expiratory pressure. Before mechanical ventilation, two of these groups received intratracheal administration of saline or exogenous surfactant at a dose of 100 mg/kg and one group received no intratracheal administration. A sixth group served as the nonventilated controls. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid was collected in which both purine concentration (microM; mean +/- SD) and protein concentration (mg/mL; mean +/- SD) were determined. Statistical differences were analyzed using the one-way analysis of variance (ANOVA) with a Student-Newman-Keul's post hoc test. Purine and protein concentrations were different between groups (ANOVA p value for purine and protein, <.0001). Both purine and protein concentrations in bronchoalveolar lavage fluid were increased in Group 45/0 (3.2 +/- 1.9 and 4.2 +/- 1.6, respectively) compared with Group 7/0 (0.4 +/- 0.1 [p < .05] and 0.4 +/- 0.2 [p < .001]) and controls (0.2 +/- 0.2 [p < .01] and 0.2 +/- 0.1 [p < .001]) and in Group 45/Na (5.8 +/- 2.5 and 4.2 +/- 0.5) compared with Group 7/0 (purine and protein, p < .001) and the controls (purine and protein, p < .001). Positive end-expiratory pressure prevented an increase in purine and protein concentrations in bronchoalveolar lavage fluid (0.4 +/- 0.3 and 0.4 +/- 0.2, respectively) compared with Group 45/0 (purine, p < .01; protein, p < .001) and Group 45/Na (purine and protein, p < .001). Surfactant instillation preceding lung overinflation reduced purine and protein concentration in bronchoalveolar lavage fluid (2.1 +/- 1.6 and 2.7 +/- 1.0) compared with Group 45/Na (purine, p < .001; protein (p < .01). Surfactant instillation reduced protein concentration compared with Group 45/0 (p < .01). CONCLUSIONS: This study shows that metabolic changes in the lung as a result of ventilation-induced lung injury are reflected by an increased level of purine in the bronchoalveolar lavage fluid and that purine may, thus, serve as an early marker for ventilation-induced lung injury. Moreover, the study shows that both exogenous surfactant and positive end-expiratory pressure reduce protein infiltration and that positive end-expiratory pressure decreases the purine level in bronchoalveolar lavage fluid after lung overinflation.

Analysis of Variance↗
PubMed1999

Conventional ventilation modes with small pressure amplitudes and high positive end-expiratory pressure levels optimize surfactant therapy.

OBJECTIVE: High-frequency oscillation studies have shown that ventilation at high end-expiratory lung volumes combined with small volume cycles at high rates best preserves exogenous surfactant and gas exchange in lavaged lungs. We investigated whether surfactant composition and gas exchange can also be preserved by conventional modes of mechanical ventilation, which combine high levels of positive end-expiratory pressure (PEEP) with small pressure amplitudes. DESIGN: Prospective, randomized, nonblinded, controlled study. SETTING: Research laboratory. SUBJECTS: Thirty male Sprague-Dawley rats. INTERVENTIONS: Rats were lung-lavaged and treated with exogenous surfactant (100 mg/kg). After 5 mins, four different ventilator settings (F(IO)2 = 1.0) were applied for 3 hrs in four groups of rats [peak inspiratory pressure (cm H2O); static PEEP (cm H2O); inspiratory/expiratory ratio; frequency], as follows: 26/2/1:2/30 (group 26/2), 26/6/1:2/30 (group 26/6), 20/10/1:2/30 (group 20/ 10-static), and 20/6/7:3/130, creating an auto PEEP of 4 cm H2O (group 20/10-auto). MEASUREMENTS AND MAIN RESULTS: In all groups, Pao2 increased immediately to prelavage values after surfactant therapy. In group 26/2, Pao2 deteriorated to postlavage values within 30 mins when PEEP was decreased to 2 cm H2O, whereas Pao2 remained stable for 3 hrs in the other groups. The Paco2 increased in groups 26/2 and 20/10-static; Paco2 could not be reduced by increasing ventilation frequency to 130 in group 20/10-static. Groups 26/6 and 20/10-auto remained normocapnic. Bronchoalveolar lavage protein concentration was higher in groups 26/2 and 26/6 compared with groups 20/10-static and 20/10-auto. There was significantly more conversion of surface active large aggregates into nonactive small aggregates in group 26/2 compared with groups 20/10-static and 20/10-auto. CONCLUSIONS: We conclude that exogenous surfactant composition is preserved by conventional modes of mechanical ventilation that use small pressure amplitudes, and adequate oxygenation is maintained by high end-expiratory pressure levels. Effective carbon dioxide removal can be achieved by applying a ventilation mode that creates auto PEEP and not by a mode that applies the same level of PEEP by static PEEP only.

Animals↗
PubMed1999

Mechanisms of ventilation-induced lung injury: physiological rationale to prevent it.

It is being increasingly realized that modes of mechanical ventilation that result in end-inspiratory alveolar overstretching and/or repeated alveolar collapse and re-expansion disturb the normal fluid balance across the alveolocapillary membrane. The effects of this include disturbance of the integrity of the endothelium and epithelium and impairment of the surfactant system and are similar to those seen in acute respiratory distress syndrome (ARDS). There is now also evidence that these modes of mechanical ventilation may result in the translocation of bacteria from the lungs into the bloodstream and the release of inflammatory mediators from the lung tissue into the systemic circulation. It may thus be speculated that mechanical ventilation may contribute to the development of multiple organ failure (MOF). Therefore, during mechanical ventilation, alveolar overstretching and the repeated collapse and re-expansion of alveoli should be prevented by ventilation modes that open up the lung and keep the lung open and ventilate with the smallest possible pressure amplitude. For the future, monitoring techniques should be developed that can evaluate, on-line, whether or not these therapeutic directives are being achieved.

Animals↗
PubMed1998

Lung overinflation without positive end-expiratory pressure promotes bacteremia after experimental Klebsiella pneumoniae inoculation.

OBJECTIVE: To determine the effect of peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) on the development of bacteremia with Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated rats. DESIGN: Prospective, randomized, animal study. SETTING: Experimental intensive care unit of a University. SUBJECTS: Eighty male Sprague Dawley rats. INTERVENTIONS: Intratracheal inoculation with 100 microliters of saline containing 3.5-5.0 x 10(5) colony forming units (CFUs) K. pneumoniae/ml. Pressure-controlled ventilation (frequency 30 bpm; I/E ratio = 1:2; FIO2 = 1.0) for 180 min at the following settings (PIP/PEEP in cmH2O): 13/3 (n = 16); 13/0 (n = 16); 30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arterial blood samples were obtained and cultured before and 180 min after mechanical ventilation and immediately before sacrifice in two groups of non-ventilated control animals (n = 8 per group). After sacrifice, the lungs were homogenized to determine the number of CFUs K. pneumoniae. MEASUREMENTS AND RESULTS: The number of CFUs recovered from the lungs was comparable in all experimental groups. After 180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0, whereas only 2, 0 and 2 animals were positive in 13/3, 13/0 and 30/10, respectively (p < 0.05 group 30/0 versus all other groups). CONCLUSIONS: These data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such PIP reduces ventilation-induced K. pneumoniae bacteremia.

Animals↗
PubMed1998

Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure.

We have assessed the effects of overinflation on surfactant function and composition in rats undergoing ventilation for 20 min with 100% oxygen at a peak inspiratory pressure of 45 cm H2O, with or without PEEP 10 cm H2O (groups 45/10 and 45/0, respectively). Mean tidal volumes were 48.4 (SEM 0.3) ml kg-1 in group 45/0 and 18.3 (0.1) ml kg-1 in group 45/10. Arterial oxygenation in group 45/0 was reduced after 20 min compared with group 45/10 (305 (71) vs 564 (10) mm Hg); maximal compliance of the P-V curve was decreased (2.09 (0.13) vs 4.16 (0.35) ml cm H2O-1 kg-1); total lung volume at a transpulmonary pressure of 5 cm H2O was reduced (6.5 (1.0) vs 18.8 (1.4) ml kg-1) and the Gruenwald index was less (0.22 (0.02) vs 0.40 (0.05)). Bronchoalveolar lavage fluid from the group of animals who underwent ventilation without PEEP had a greater protein concentration (2.18 (0.11) vs 0.76 (0.22) mg ml-1) and a greater minimal surface tension (37.2 (6.3) vs 24.5 (2.8) mN m-1) than in those who underwent ventilation with PEEP. Group 45/0 had an increase in non-active to active total phosphorus compared with nonventilated controls (0.90 (0.16) vs 0.30 (0.07)). We conclude that ventilation in healthy rats with peak inspiratory pressures of 45 cm H2O without PEEP for 20 min caused severe impairment of pulmonary surfactant composition and function which can be prevented by the use of PEEP 10 cm H2O.

Animals↗
PubMed1998

Exogenous surfactant preserves lung function and reduces alveolar Evans blue dye influx in a rat model of ventilation-induced lung injury.

BACKGROUND: Changes in pulmonary edema infiltration and surfactant after intermittent positive pressure ventilation with high peak inspiratory lung volumes have been well described. To further elucidate the role of surfactant changes, the authors tested the effect of different doses of exogenous surfactant preceding high peak inspiratory lung volumes on lung function and lung permeability. METHODS: Five groups of Sprague-Dawley rats (n = 6 per group) were subjected to 20 min of high peak inspiratory lung volumes. Before high peak inspiratory lung volumes, four of these groups received intratracheal administration of saline or 50, 100, or 200 mg/kg body weight surfactant; one group received no intratracheal administration. Gas exchange was measured during mechanical ventilation. A sixth group served as nontreated, nonventilated controls. After death, all lungs were excised, and static pressure-volume curves and total lung volume at a transpulmonary pressure of 5 cm H2O were recorded. The Gruenwald index and the steepest part of the compliance curve (Cmax) were calculated. A bronchoalveolar lavage was performed; surfactant small and large aggregate total phosphorus and minimal surface tension were measured. In a second experiment in five groups of rats (n = 6 per group), lung permeability for Evans blue dye was measured. Before 20 min of high peak inspiratory lung volumes, three groups received intratracheal administration of 100, 200, or 400 mg/ kg body weight surfactant; one group received no intratracheal administration. A fifth group served as nontreated, nonventilated controls. RESULTS: Exogenous surfactant at a dose of 200 mg/kg preserved total lung volume at a pressure of 5 cm H2O, maximum compliance, the Gruenwald Index, and oxygenation after 20 min of mechanical ventilation. The most active surfactant was recovered in the group that received 200 mg/kg surfactant, and this dose reduced minimal surface tension of bronchoalveolar lavage to control values. Alveolar influx of Evans blue dye was reduced in the groups that received 200 and 400 mg/kg exogenous surfactant. CONCLUSIONS: Exogenous surfactant preceding high peak inspiratory lung volumes prevents impairment of oxygenation, lung mechanics, and minimal surface tension of bronchoalveolar lavage fluid and reduces alveolar influx of Evans blue dye. These data indicate that surfactant has a beneficial effect on ventilation-induced lung injury.

Animals↗
PubMed1997

Combining partial liquid ventilation with nitric oxide to improve gas exchange in acute lung injury.

OBJECTIVE: To assess the effects of increasing concentrations of inhaled nitric oxide (NO) during incremental dosages of partial liquid ventilation (PLV) on gas exchange, hemodynamics, and oxygen transport in pigs with induced acute lung injury (ALI). DESIGN: Prospective experimental study. SETTING: Experimental intensive care unit of a university. SUBJECTS: 6 pigs with induced ALI. INTERVENTIONS: Animals were surfactant-depleted by lung lavage to a partial pressure of oxygen in arterial blood (PaO2) < 100 mmHg. They then received four incremental doses of 5 ml/kg perflubron (Liqui-Vent). Between each dose the animals received 0, 10, 20, 30, 40, and 0 parts per million (ppm) NO. MEASUREMENTS AND MAIN RESULTS: Blood gases, hemodynamic parameters, and oxygen delivery were measured after each dose of perflubron as well as after each NO concentration. Perflubron resulted in a dose-dependent increase in PaO2. At each perflubron dose, additional NO inhalation resulted in a further significant (ANOVA, p < 0.05) increase in PaO2, with a maximum effect at 30 +/- 10 ppm NO. The 5 ml/kg perflubron dose led to a significant decrease in mean pulmonary artery pressure, which decreased further with higher NO concentrations. CONCLUSIONS: PLV can be combined with NO administration and results in a cumulative effect on arterial oxygenation and to a decrease in pulmonary artery pressure, without having any deleterious effect on measured systemic hemodynamic parameters.

Administration, Inhalation↗
PubMed1997

Mechanisms of acute respiratory distress syndrome: role of surfactant changes and mechanical ventilation.

Acute respiratory distress syndrome (ARDS) is a condition characterized by a high permeability oedema due to loss of the integrity of the alveolo-capillary barrier with impairment of normal surfactant function, resulting in an increased collapse tendency of the alveoli. Mechanical ventilation on such alveoli with repeated alveolar collapse and subsequent reexpansion results in severe lung parenchymal injury and may induce further surfactant impairment. This cam be prevented by maintaining alveolar volume at end-expiration by means of sufficient levels of positive end-expiratory pressure (PEEP). Recent evidence from experimental studies has shown that ventilator modes which allow end-expiratory collapse can induce bacterial translocation from the lung into the bloodstream and trigger the release of inflammatory mediators, which can also be presented by maintaining end-expiratory alveolar volume. These data suggest that the interaction between surfactant changes and mechanical ventilation may play a role in the transition of ARDS into the systematic inflammatory disease process of multiple system organ failure (MSOF).

Humans↗