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1.
Crit Care Med ; 38(11): 2207-14, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20818231

ABSTRACT

OBJECTIVE: In acute lung injury, recruitment maneuvers have been used to open collapsed lungs and set positive end-expiratory pressure, but their effectiveness may depend on the degree of lung injury. This study uses a single experimental model with different degrees of lung injury and tests the hypothesis that recruitment maneuvers may have beneficial or deleterious effects depending on the severity of acute lung injury. We speculated that recruitment maneuvers may worsen lung mechanical stress in the presence of alveolar edema. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University research laboratory. SUBJECTS: Thirty-six Wistar rats randomly divided into three groups (n = 12 per group). INTERVENTIONS: In the control group, saline was intraperitoneally injected, whereas moderate and severe acute lung injury animals received paraquat intraperitoneally (20 mg/kg [moderate acute lung injury] and 25 mg/kg [severe acute lung injury]). After 24 hrs, animals were further randomized into subgroups (n = 6/each) to be recruited (recruitment maneuvers: 40 cm H2O continuous positive airway pressure for 40 secs) or not, followed by 1 hr of protective mechanical ventilation (tidal volume, 6 mL/kg; positive end-expiratory pressure, 5 cm H2O). MEASUREMENTS AND MAIN RESULTS: Only severe acute lung injury caused alveolar edema. The amounts of alveolar collapse were similar in the acute lung injury groups. Static lung elastance, viscoelastic pressure, hyperinflation, lung, liver, and kidney cell apoptosis, and type 3 procollagen and interleukin-6 mRNA expressions in lung tissue were more elevated in severe acute lung injury than in moderate acute lung injury. After recruitment maneuvers, static lung elastance, viscoelastic pressure, and alveolar collapse were lower in moderate acute lung injury than in severe acute lung injury. Recruitment maneuvers reduced interleukin-6 expression with a minor detachment of the alveolar capillary membrane in moderate acute lung injury. In severe acute lung injury, recruitment maneuvers were associated with hyperinflation, increased apoptosis of lung and kidney, expression of type 3 procollagen, and worsened alveolar capillary injury. CONCLUSIONS: In the presence of alveolar edema, regional mechanical heterogeneities, and hyperinflation, recruitment maneuvers promoted a modest but consistent increase in inflammatory and fibrogenic response, which may have worsened lung function and potentiated alveolar and renal epithelial injury.


Subject(s)
Acute Lung Injury/therapy , Continuous Positive Airway Pressure , Pulmonary Atelectasis/etiology , Pulmonary Edema/etiology , Acute Lung Injury/complications , Acute Lung Injury/pathology , Acute Lung Injury/physiopathology , Animals , Collagen Type III/biosynthesis , Interleukin-6/biosynthesis , Kidney/pathology , Liver/pathology , Lung/pathology , Microscopy, Electron, Transmission , Pulmonary Alveoli/injuries , Pulmonary Alveoli/pathology , Pulmonary Alveoli/physiopathology , Pulmonary Atelectasis/therapy , Pulmonary Edema/therapy , Rats , Rats, Wistar , Respiration, Artificial , Respiratory Mechanics/physiology
2.
Respir Physiol Neurobiol ; 169(3): 271-81, 2009 Dec 31.
Article in English | MEDLINE | ID: mdl-19819351

ABSTRACT

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT=6 ml/kg and positive end-expiratory pressure (PEEP)=5 cmH(2)O for 1h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP=40 cmH(2)O), with interposed periods of PIP=10 cmH(2)O above a PEEP=15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.


Subject(s)
Acute Lung Injury/physiopathology , Acute Lung Injury/therapy , Lung/pathology , Lung/ultrastructure , Positive-Pressure Respiration/methods , Respiratory Mechanics/physiology , Acute Lung Injury/pathology , Animals , Apoptosis/physiology , Collagen Type III/genetics , Collagen Type III/metabolism , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Gene Expression Regulation/physiology , In Situ Nick-End Labeling/methods , Lung/metabolism , Lung Volume Measurements , Microscopy, Electron, Transmission/methods , RNA, Messenger/metabolism , Rats , Rats, Wistar , Respiratory Function Tests/methods , Statistics, Nonparametric
3.
Crit Care Med ; 37(3): 1011-7, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19237911

ABSTRACT

OBJECTIVE: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomized, and controlled experimental study. SETTING: University research laboratory. SUBJECTS: Wistar rats were randomly assigned to control (C) [saline (0.1 mL), intraperitoneally] and ALI [paraquat (15 mg/kg), intraperitoneally] groups. MEASUREMENTS AND MAIN RESULTS: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H2O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (DeltaP2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and DeltaP2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. CONCLUSIONS: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and DeltaP2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful.


Subject(s)
Acute Lung Injury/therapy , Positive-Pressure Respiration/adverse effects , Animals , Lung Diseases/etiology , Positive-Pressure Respiration/methods , Rats , Rats, Wistar
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