American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 1998
Effects of a neutrophil elastase inhibitor (ONO-5046) on acute pulmonary injury induced by tumor necrosis factor alpha (TNFalpha) and activated neutrophils in isolated perfused rabbit lungs.
The aim of this study was to examine the effect of ONO-5046, a neutrophil elastase (NE) inhibitor, on a model of acute lung injury induced by tumor necrosis factor alpha (TNFalpha) and phorbol myristate acetate (PMA)-activated neutrophils in isolated perfused rabbit lungs. 120 min after TNFalpha (4,000 JRU/ml) was injected into the pulmonary artery (PA), 5 x 10(7) PMA-stimulated neutrophils were infused into the PA together with 1251-rabbit serum albumin (RSA). In the ONO-5046-treated group (ONO), ONO-5046 (20 mg/kg/h) was continuously infused during the experimental period from 30 min prior to neutrophil administration. Saline, the ONO-5046 vehicle, was infused instead of ONO-5046 in the positive control group (ALD) and nonactivated neutrophils were infused without TNFalpha in the negative control group (Cont). ⋯ ALD group had higher TM levels in the perfusate and showed decreased expression of TM on the vascular endothelium compared to Cont and ONO group, suggesting that there was shedding of TM on endothelium and ONO-5046 attenuated a shedding of TM. In conclusion, ONO-5046 attenuated acute lung injury by inhibiting the alveolar epithelial and vascular endothelial injury triggered by activated neutrophils. NE appears to play an important role in the neutrophil-induced increase of pulmonary epithelial and microvascular permeability observed in acute lung injury.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Randomized Controlled Trial Comparative Study Clinical Trial Controlled Clinical TrialEffects of flow triggering on breathing effort during partial ventilatory support.
The effects of flow triggering (FT) as compared with pressure triggering (PT) on breathing effort have been the focus of several studies, and discrepant results have been reported. In the initial part of our study, a lung model was used to quantify triggering effort (airway pressure-time product, PTPaw) for a range of sensitivity settings in nine new-generation ventilators. A ventilator providing both FT and PT was then used to compare these systems during pressure-support (PSV) and volume-targeted assist-control ventilation (ACV) in eight ventilator-dependent patients, using sensitivity settings (2 L/min for FT and -2 cm H2O for PT) that had proven significantly different in the initial bench study. ⋯ By contrast, no differences were found when FT was used during ACV. Although FT reduced triggering effort in both modes (p < 0.001), the effects observed during the post-trigger phase differed, and explained the discrepant results between the two modes. We conclude that FT more effectively reduces breathing effort when used in conjunction with a pressure-targeted mode than with a volume-targeted mode, especially when flow delivery is close to or below demand.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Clinical Trial Controlled Clinical TrialContribution of the endotracheal tube and the upper airway to breathing workload.
The influence of the endotracheal tube (ETT) during a T-piece trial remains controversial. Our aim was to compare the work of breathing of 14 successfully extubated patients at the end of a 2-h trial (T) and after extubation (E) of the trachea, and to assess, using the acoustic reflection method, the resistance of the endotracheal tube and of the supraglottic airway as well as their related work. We found that the work of breathing of the patients was identical between T and E (1.72 +/- 0.59 versus 1.63 +/- 0.45 J/L; p = 0.50 and 23.5 +/- 10.6 versus 22.6 +/- 9.7 J/min; p = 0.70). ⋯ The work caused by the ETT amounted to 11.0 +/- 3.9% of the total work of breathing. The supraglottic airway resistance was in the normal range and was significantly smaller than the endotracheal tube resistance (0.79 +/- 0.4 versus 1.43 +/- 0.31 cm H2O x s/L; p = 0.008, flow = 0.25 L/s). We conclude that a 2-h trial of spontaneous breathing through an endotracheal tube well mimics the work of breathing performed after extubation, in patients who pass a weaning trial and do not require reintubation.
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Am. J. Respir. Crit. Care Med. · Jan 1998
Effects of ventilation strategies on the efficacy of exogenous surfactant therapy in a rabbit model of acute lung injury.
We evaluated the effects of various ventilation strategies on the efficacy of exogenous surfactant therapy in lung-injured adult rabbits. Lung injury was induced by repetitive whole-lung saline lavage followed by mechanical ventilation. Three hours after the final lavage, 100 mg lipid/kg bovine lipid extract surfactant was instilled. ⋯ Animals ventilated with the low-VT modes (Low VT [5 cm H2O] and Low VT [9 cm H2O]) had higher PaO2 values (430 +/- 7 mm Hg and 425 +/- 18 mm Hg versus 328 +/- 13 mm Hg) and higher percentages of surfactant in large aggregate forms (83 +/- 2% and 82 +/- 2% versus 67 +/- 4%) at 3 h after treatment than did the Normal VT (5 cm H2O) group (p < 0.05). Increasing the PEEP level was beneficial for a short period after surfactant administration to maintain oxygenation, but did not affect exogenous surfactant aggregate conversion. We speculate that ventilation strategies resulting in low exogenous surfactant aggregate conversion will result in superior physiologic responses to exogenous surfactant.