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Michael A Matthay

Publications and source records attributed to Michael A Matthay.

At least 109 records · Page 6Linked to original sources
PubMed2003

Cytokine-mediated inflammation in acute lung injury.

Clinical acute lung injury (ALI) is a major cause of acute respiratory failure in critically ill patients. There is considerable experimental and clinical evidence that pro- and anti-inflammatory cytokines play a major role in the pathogenesis of inflammatory-induced lung injury from sepsis, pneumonia, aspiration, and shock. A recent multi-center clinical trial found that a lung-protective ventilatory strategy reduces mortality by 22% in patients with ALI. Interestingly, this protective ventilatory strategy was associated with a marked reduction in the number of neutrophils and the concentration of pro-inflammatory cytokines released into the airspaces of the injured lung. Further research is needed to establish the contribution of cytokines to both the pathogenesis and resolution of ALI.

Animals↗
PubMed2003

Prognostic value of surfactant proteins A and D in patients with acute lung injury.

OBJECTIVE: The primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes. DESIGN: Observational study. SETTING: Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital. PATIENTS: Thirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference. INTERVENTIONS: Undiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients. MEASUREMENTS AND MAIN RESULTS: The concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p = .03) and in patients with an absence of intact alveolar fluid clearance (p =.03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p = .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL; p = .02). CONCLUSIONS: These results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis.

Adult↗
PubMed2003

Pulmonary edema fluid antioxidants are depressed in acute lung injury.

OBJECTIVE: To test the hypothesis that low concentrations of distal airspace water-soluble antioxidants are associated with acute lung injury. DESIGN: Prospective, cohort study. SETTING: Medical intensive care unit of two tertiary care hospitals. SUBJECTS: Subjects were 29 patients with acute lung injury and 23 normal, healthy, volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pulmonary edema fluid from subjects with acute lung injury was aspirated immediately after intubation. Compared with the bronchoalveolar lavage from normal subjects (corrected for dilution using urea concentrations), undiluted edema fluid from acute lung injury subjects had significantly lower concentrations of the antioxidants urate (757 +/- 232 microM vs. 328 +/- 75 microM), glutathione (138 +/- 25 microM vs. 7 +/- 4 microM), and ascorbate (85 +/- 21 microM vs. 27 +/- 10 microM). CONCLUSIONS: Acute lung injury is associated with decreased concentrations of water-soluble antioxidants in the distal airspaces. In acute lung injury, the distal airspace antioxidants ascorbate, urate, and glutathione may play a role in attenuating lung injury.

Adult↗
PubMed2003

Effects of recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome ventilated with high positive end-expiratory pressure.

OBJECTIVE: Positive end-expiratory pressure (PEEP) and recruitment maneuvers (RMs) may partially reverse atelectasis and reduce ventilation-associated lung injury. The purposes of this study were to assess a) magnitude and duration of RM effects on arterial oxygenation and on requirements for oxygenation support (Fio2/PEEP) in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) receiving ventilation with low tidal volumes and high levels of PEEP; and b) frequency of adverse respiratory and circulatory events attributable to RMs. DESIGN: Prospective, randomized, crossover study. SETTING: Thirty-four intensive care units at 19 hospitals. PATIENTS: Seventy-two patients with early ALI/ARDS. Baseline PEEP and Fio2 were 13.8 +/- 3.0 cm H2O and 0.39 +/- 0.10, respectively (mean +/- sd). INTERVENTIONS: We conducted RMs by applying continuous positive airway pressure of 35-40 cm H2O for 30 secs. We conducted sham RMs on alternate days. We monitored oxyhemoglobin saturation by pulse oximetry (SpO2), Fio2/PEEP, blood pressure, and heart rate for 8 hrs after RMs and sham RMs. We examined chest radiographs for barotrauma. MEASUREMENTS AND MAIN RESULTS: Responses to RMs were variable. Greatest increments from baseline SpO2 within 10 mins after RMs were larger than after sham RMs (1.7 +/- 0.2 vs. 0.6 +/- 0.3 %, mean +/- SEM, p < .01). Systolic blood pressure decreased more +/- 1.1 mm Hg, p < .01). Changes in Fio2/PEEP requirements were not significantly different at any time after RMs vs. sham RMs. Barotrauma was apparent on first radiographs after one RM and one sham RM. CONCLUSIONS: In ALI/ARDS patients receiving mechanical ventilation with low tidal volumes and high PEEP, short-term effects of RMs as conducted in this study are variable. Beneficial effects on gas exchange in responders appear to be of brief duration. More information is needed to determine the role of recruitment maneuvers in the management of ALI/ARDS.

Blood Pressure↗
PubMed2003

Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation.

OBJECTIVE: To determine whether soluble intercellular adhesion molecule (sICAM)-1, a biological marker of alveolar epithelial and lung endothelial injury and alveolar macrophage activation, is elevated in the plasma of pediatric patients with acute lung injury and to examine whether elevated plasma sICAM-1 levels correlate with two clinically relevant outcomes, mortality and the duration of mechanical ventilation. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care units at an urban children's hospital and a tertiary university medical center. PATIENTS: Eighty-three pediatric patients with acute lung injury and five intubated controls. INTERVENTIONS: Plasma sICAM-1 levels were measured on days 1 and 2 of acute lung injury in pediatric patients and on day 1 of mechanical ventilation in control patients. MEASUREMENTS AND MAIN RESULTS: Plasma sICAM-1 levels were significantly higher in patients with acute lung injury compared with controls (966 +/- 830 vs. 251 +/- 168 ng/mL, p <.05). Levels of sICAM-1 were also significantly higher on days 1 and 2 of acute lung injury in nonsurvivors and in patients requiring prolonged duration of mechanical ventilation. Also, plasma sICAM-1 levels >1000 ng/mL had a high specificity for identifying nonsurvivors of acute lung injury. CONCLUSIONS: Early elevation of sICAM-1 in the plasma of pediatric patients with acute lung injury is associated with increased risk of death or prolonged duration of mechanical ventilation.

Acute Disease↗
PubMed2002

Science review: mechanisms of ventilator-induced injury.

Acute respiratory distress syndrome (ARDS) and acute lung injury are among the most frequent reasons for intensive care unit admission, accounting for approximately one-third of admissions. Mortality from ARDS has been estimated as high as 70% in some studies. Until recently, however, no targeted therapy had been found to improve patient outcome, including mortality. With the completion of the National Institutes of Health-sponsored Acute Respiratory Distress Syndrome Network low tidal volume study, clinicians now have convincing evidence that ventilation with tidal volumes lower than those conventionally used in this patient population reduces the relative risk of mortality by 21%. These data confirm the long-held suspicion that the role of mechanical ventilation for acute hypoxemic respiratory failure is more than supportive, in that mechanical ventilation can also actively contribute to lung injury. The mechanisms of the protective effects of low tidal volume ventilation in conjunction with positive end expiratory pressure are incompletely understood and are the focus of ongoing studies. The objective of the present article is to review the potential cellular mechanisms of lung injury attributable to mechanical ventilation in patients with ARDS and acute lung injury.

Cytokines↗
PubMed2002

Hypoxia and beta 2-agonists regulate cell surface expression of the epithelial sodium channel in native alveolar epithelial cells.

Alveolar hypoxia may impair sodium-dependent alveolar fluid transport and induce pulmonary edema in rat and human lung, an effect that can be prevented by the inhalation of beta(2)-agonists. To investigate the mechanism of beta(2)-agonist-mediated stimulation of sodium transport under conditions of moderate hypoxia, we examined the effect of terbutaline on epithelial sodium channel (ENaC) expression and activity in cultured rat alveolar epithelial type II cells exposed to 3% O(2) for 24 h. Hypoxia reduced transepithelial sodium current and amiloride-sensitive sodium channel activity without decreasing ENaC subunit mRNA or protein levels. The functional decrease was associated with reduced abundance of ENaC subunits (especially beta and gamma) in the apical membrane of hypoxic cells, as quantified by biotinylation. cAMP stimulation with terbutaline reversed the hypoxia-induced decrease in transepithelial sodium transport by stimulating sodium channel activity and markedly increased the abundance of beta-and gamma-ENaC in the plasma membrane of hypoxic cells. The effect of terbutaline was prevented by brefeldin A, a blocker of anterograde transport. These novel results establish that hypoxia-induced inhibition of amiloride-sensitive sodium channel activity is mediated by decreased apical expression of ENaC subunits and that beta(2)-agonists reverse this effect by enhancing the insertion of ENaC subunits into the membrane of hypoxic alveolar epithelial cells.

Adrenergic beta-Agonists↗
PubMed2002

Pleural surface fluorescence measurement of Na+ and Cl- transport across the air space-capillary barrier.

We developed a pleural surface fluorescence method to measure Na(+) and Cl(-) transport in perfused mouse lungs. The air space was filled with aqueous fluid containing membrane-impermeant fluorescent indicators of Cl(-) (lucigenin) or Na(+) (Sodium Green). After instillation of a Cl(-)-free solution into the air space, an increase in perfusate Cl(-) concentration from 0 to 30 mM produced a decrease in surface lucigenin fluorescence (6.5%/min) corresponding to Cl(-) influx of 1.0 mM/min. Cl(-) influx was increased to 2.1 +/- 0.3 mM/min by forskolin, and the increase was inhibited by glibenclamide. cAMP-stimulated Cl(-) influx was decreased by 57% in CFTR null mice. After instillation of a Na(+)-free solution into the air space, an increase in perfusate Na(+) concentration from 0 to 30 mM gave increased Sodium Green fluorescence (Na(+) influx of 1.2 mM/min), which increased approximately fivefold after cAMP agonists. Cl(-) and Na(+) transport were not affected in lungs from mice lacking aquaporins AQP1 or AQP5. Our results establish a pleural surface fluorescence method to measure unidirectional Cl(-) and Na(+) flux in intact lung and provide evidence for cAMP-stimulated transcellular Cl(-) and Na(+) transport.

Acridines↗
PubMed2002

Evidence against aquaporin-1-dependent CO2 permeability in lung and kidney.

AQP1-dependent CO2 transport has been suggested from the increased CO2 permeability in Xenopus oocytes expressing AQP1. Potential implications of this finding include AQP1-facilitated CO2 exchange in mammalian lung and HCO3-/CO2 transport in kidney proximal tubule. We reported previously that: (a) CO2 permeability in erythrocytes was not affected by AQP1 deletion, (b) CO2 permeability in liposomes was not affected by AQP1 reconstitution despite a 100-fold increased water permeability, and (c) CO2 blow-off by the lung in living mice was not impaired by AQP1 deletion. We extend these observations by direct measurement of CO2 permeabilities in lung and kidney. CO2 transport across the air-space-capillary barrier in isolated perfused lungs was measured from changes in air-space fluid pH in response to addition/removal of HCO3-/CO2 from the pulmonary artery perfusate. The pH was measured by pleural surface fluorescence of a pH indicator (BCECF-dextran) in the air-space fluid. Air-space fluid pH equilibrated rapidly (t(1/2) approximately 6 s) in response to addition/removal of HCO3-/CO2. However, the kinetics of pH change was not different in lungs of mice lacking AQP1, AQP5 or AQP1/AQP5 together, despite an up to 30-fold reduction in water permeability. CO2 transport across BCECF-loaded apical membrane vesicles from kidney proximal tubule was measured from the kinetics of intravesicular acidification in response to rapid mixing with a HCO3-/CO2 solution. Vesicles rapidly acidified (t(1/2) approximately 10 ms) in response to HCO3-/CO2 addition. However the acidification rate was not different in kidney vesicles from AQP1-null mice despite a 20-fold reduction in water permeability. The results provide direct evidence against physiologically significant transport of CO2 by AQP1 in mammalian lung and kidney.

Algorithms↗
PubMed2002

Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure.

OBJECTIVE: Experimental studies demonstrate that beta-adrenergic agonists markedly stimulate alveolar fluid clearance if concentrations of 10(-6) M are achieved in alveolar fluid. However, no studies have determined whether aerosolized beta-adrenergic agonists are delivered to the distal air spaces of the lung in therapeutic concentrations in patients with pulmonary edema. DESIGN AND SETTING: This retrospective study measured albuterol levels in the pulmonary edema fluid and plasma from mechanically ventilated patients with pulmonary edema from a hydrostatic mechanism ( n=10) or from acute lung injury ( n=12). MEASUREMENTS AND RESULTS: After a total aerosolized albuterol dose of 4.2+/-3.2 mg in the prior 6 h the median pulmonary edema fluid albuterol level was 1,250 ng/ml (10(-6) M) in patients with hydrostatic pulmonary edema; after 3.5+/-2.6 mg the figure was 1,240 ng/ml (10(-6) M) in patients with pulmonary edema from acute lung injury. Plasma albuterol levels were much lower, with a median of 5.2 ng/ml (0.01 x 10(-6) M) in patients with hydrostatic pulmonary edema and 3.1 ng/ml (0.01 x 10(-6) M) in patients with pulmonary edema from acute lung injury. CONCLUSIONS: These results provide the first evidence that levels of beta-adrenergic agonists that are physiologically efficacious in experimental models can be achieved with conventional delivery systems in ventilated, critically ill patients with acute respiratory failure from pulmonary edema.

APACHE↗
PubMed2002

Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome.

BACKGROUND: No single pulmonary-specific variable, including the severity of hypoxemia, has been found to predict the risk of death independently when measured early in the course of the acute respiratory distress syndrome. Because an increase in the pulmonary dead-space fraction has been described in observational studies of the syndrome, we systematically measured the dead-space fraction early in the course of the illness and evaluated its potential association with the risk of death. METHODS: The dead-space fraction was prospectively measured in 179 intubated patients, a mean (+/-SD) of 10.9+/-7.4 hours after the acute respiratory distress syndrome had developed. Additional clinical and physiological variables were analyzed with the use of multiple logistic regression. The study outcome was mortality before hospital discharge. RESULTS: The mean dead-space fraction was markedly elevated (0.58+/-0.09) early in the course of the acute respiratory distress syndrome and was higher among patients who died than among those who survived (0.63+/-0.10 vs. 0.54+/-0.09, P<0.001). The dead-space fraction was an independent risk factor for death: for every 0.05 increase, the odds of death increased by 45 percent (odds ratio, 1.45; 95 percent confidence interval, 1.15 to 1.83; P=0.002). The only other independent predictors of an increased risk of death were the Simplified Acute Physiology Score II, an indicator of the severity of illness (odds ratio, 1.06; 95 percent confidence interval, 1.03 to 1.08; P<0.001) and quasistatic respiratory compliance (odds ratio, 1.06; 95 percent confidence interval, 1.01 to 1.10; P=0.01). CONCLUSIONS: Increased dead-space fraction is a feature of the early phase of the acute respiratory distress syndrome. Elevated values are associated with an increased risk of death.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome.

The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) have not been clearly established. Using data from ARDS Network randomized controlled trials, we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma. We studied airway pressures at three exposure intervals: baseline, one day preceding the barotrauma event (one-day lag), and concurrent with the barotrauma event. During the first four study days, the cumulative incidence of barotrauma was 13% (95% confidence interval [CI] 10.6 to 15.6%). In a forward stepwise Cox proportional hazards analysis using time-dependent variables, higher concurrent positive end-expiratory pressure (PEEP) was associated with an increased risk of early barotrauma (relative hazard [RH] 1.67 per 5-cm H2O increment; 95% CI 1.35-2.07). Once concurrent PEEP was selected into the model, no other airway pressure was related to barotrauma, including plateau pressure. In the multivariate analysis, higher concurrent PEEP was also related to a greater risk of barotrauma (RH 1.93; 95% CI 1.44-2.60), controlling for age, ventilator group (6 versus 12 ml/kg), baseline PEEP, baseline plateau pressure, baseline tidal volume, Acute Physiology and Chronic Health Evaluation score, vasopressor use, serum albumin, hepatic failure, and coagulopathy. When one-day lagged values of PEEP were analyzed, higher PEEP was associated with a greater risk of barotrauma (RH 1.38 per 5-cm H2O increment; 95% CI 1.09-1.76). Controlling for the covariates, higher PEEP was related to an increased risk of barotrauma (RH 1.50; 95% CI 0.98- 2.30). In conclusion, higher PEEP may increase the likelihood of early barotrauma in ALI/ARDS.

Airway Resistance↗