Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Activated neutrophils contribute to the development of ventilator-induced lung injury (VILI) caused by high-pressure mechanical ventilation. However, exact cellular and molecular mechanisms have not been conclusively studied. Our investigation aimed to examine expression of adhesion molecules by both neutrophils and macrophages in lung lavage fluids of rats with VILI. Further, involvement of proinflammatory (tumor necrosis factor-alpha) and profibrogenetic (transforming growth factor-beta 1) mediators was analyzed at mRNA level in lung tissue. Wistar rats were ventilated by high pressure (45 cm H(2)O of peak inspiratory pressure, n = 23) or low pressure (7 cm H(2)O, n = 13) with 0 positive end-expiratory pressure. After 40 min of comparative ventilation, lung lavage was performed in 20 rats from the experimental group and 10 from the control for immunofluorescence analysis with anti-Mac-1 and anti-ICAM-1 monoclonal antibodies. The lung tissues from remaining rats were subjected to pathological and reverse transcription-polymerase chain reaction examinations. Although there was no significant change of PaO(2) in the low-pressure group, PaO(2) was decreased in the high-pressure group. The high-pressure group also had greater neutrophil infiltration into alveolar spaces, upregulation of CD54 and CD11b on alveolar macrophages, and more transforming growth factor-beta 1 mRNA in lung tissues. Tumor necrosis factor-alpha was not involved in the pathogenesis of the severe VILI observed. Histologic findings also demonstrated more infiltrating neutrophils, destructive change of the alveolar wall, and deposition of matrix in the high-pressure group. These results suggest that a series of proinflammatory reactions and profibrogenetic process may be involved in the course of VILI.

Related collections

Most cited references 29

Record: found
Abstract: found
Article: not found

Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.

M. B. P. Amato, C Barbas, D M Medeiros … (1998)

In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes. After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37). As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.

0 comments Cited 549 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993.

Gary K Steinberg, J Milberg, Ian Davis … (1995)

To analyze temporal trends in acute respiratory distress syndrome (ARDS) fatality rates since 1983 at one institution. Cohort. Intensive care units of a large county hospital. Consecutive adult patients (> or = 18 years of age) meeting ARDS criteria were identified through daily surveillance of intensive care units (N = 918 from 1983 through 1993). The major causes were sepsis syndrome in 37% and major trauma in 25%; 37% had other risks. Sixty-five percent were male. The median age was 45 years (range, 18 to 92 years); 70% were younger than 60 years. Hospital mortality. Overall fatality rates showed no trend from 1983 to 1987, declined slightly in 1988 and 1989, and decreased to a low of 36% in 1993 (95% confidence interval, 25% to 46%). The crude rates were largely unchanged after adjustment for age, ARDS risk, and gender distribution. While patients both younger than 60 years and 60 years or older experienced declines in fatality rate, the larger decrease occurred in the younger cohort. In sepsis patients, ARDS fatality rates declined steadily, from 67% in 1990 to 40% in 1993 (95% confidence interval, 23% to 57%). The decline in sepsis-related ARDS fatality was confined largely to patients less than 60 years of age. Trauma patients and all other patients also experienced declines in fatality rates after 1987, although these trends were not as strong and consistent as in the sepsis population. In this large series, we observed a significant decrease in fatality rates occurring largely in patients younger than 60 years and in those with sepsis syndrome as their risk for ARDS. We are unable to determine the extent to which experimental therapies or other changes in treatment have contributed to the observed decline in the ARDS fatality rate. Institution-specific rates and temporal trends in ARDS fatality rates should be considered in clinical trials designed to prevent ARDS and the high mortality associated with this syndrome.