Showing papers by "Michael A. Matthay published in 1998"
TL;DR: The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution.
Abstract: The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last 10 years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathologic features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.
453 citations
TL;DR: The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution.
Abstract: The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last ten years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.
277 citations
TL;DR: The purpose of this study was to test whether osmotic water permeability in type I alveolar epithelial cells is high enough to account for the high Pf of the intact lung.
Abstract: Water permeability measured between the airspace and vasculature in intact sheep and mouse lungs is high. More than 95% of the internal surface area of the lung is lined by alveolar epithelial type I cells. The purpose of this study was to test whether osmotic water permeability (Pf) in type I alveolar epithelial cells is high enough to account for the high Pf of the intact lung. Pf measured between the airspace and vasculature in the perfused fluid-filled rat lung by the pleural surface fluorescence method was high (0.019 ± 0.004 cm/s at 12°C) and weakly temperature-dependent (activation energy 3.7 kcal/mol). To resolve the contributions of type I and type II alveolar epithelial cells to lung water permeability, Pf was measured by stopped-flow light scattering in suspensions of purified type I or type II cells obtained by immunoaffinity procedures. In response to a sudden change in external solution osmolality from 300 to 600 mOsm, the volume of type I cells decreased rapidly with a half-time (t1/2) of 60–80 ms at 10°C, giving a plasma membrane Pf of 0.06–0.08 cm/s. Pf in type I cells was independent of osmotic gradient size and was weakly temperature-dependent (activation energy 3.4 kcal/mol). In contrast, t1/2 for type II cells in suspension was much slower, ≈1 s; Pf for type II cells was 0.013 cm/s. Vesicles derived from type I cells also had a very high Pf of 0.06–0.08 cm/s at 10°C that was inhibited 95% by HgCl2. The Pf in type I cells is the highest measured for any mammalian cell membrane and would account for the high water permeability of the lung.
230 citations
TL;DR: Results show that HGF and KGF are active in the alveolar space early in ALI, probably mediating early events in lung repair, and that increased levels of HGF in edema fluid may have prognostic value early inALI.
Abstract: Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are among the most potent mitogens identified for alveolar type II epithelial cells and may have other important functions in repair of the alveolar epithelium in acute lung injury (ALI). However, neither growth factor has been identified in the distal air spaces or plasma of patients with ALI. The goals of this study were to determine: (1) whether HGF and KGF are present in pulmonary edema fluid from patients with ALI and control patients with hydrostatic pulmonary edema; (2) whether HGF and KGF are biologically active in pulmonary edema; and (3) whether HGF or KGF levels are associated with clinical outcome. Pulmonary edema and plasma samples were obtained within 48 h of onset of acute pulmonary edema requiring mechanical ventilation in 26 patients with ALI and 11 control patients with hydrostatic edema. HGF and KGF concentrations were measured with enzyme-linked immunosorbent assays (ELISAs). The median (25th to 75th percentiles) conce...
117 citations
TL;DR: Although obstetric pulmonary edema is associated with extensive radiographic infiltrates and severe hypoxemia, resolution occurs rapidly in most patients, limiting the need for intensive care support.
75 citations
TL;DR: Evidence is provided that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the transport capacity of the alveolars epithelium, even though the expression of epithelial sodium channels is reduced and the uptake of 22Na per cell is also reduced.
Abstract: Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). An isosmolar Ringer lactate solution with 5% bovine serum ...
68 citations
TL;DR: It is demonstrated that potentially therapeutic concentrations of TMAO can be sustained in mice in vivo, permitting the testing of chemical chaperones in transgenic mouse models of diseases caused by defective protein trafficking.
54 citations
TL;DR: The rate of AFC in nonperfused mouse lungs was significantly faster than in prior studies of non perfused lungs in rats and sheep and the stimulated clearance rate in mice was similar to the fast rates of AFC that were reported in patients recovering from hydrostatic pulmonary edema.
Abstract: Because the availability of transgenic mice makes it possible to examine the contribution of single genes to in vivo function, we developed a simple in situ mouse model that can be used to quantify...
47 citations
TL;DR: The epidemiology of three important complications of venous thromboembolism, stress-related upper gastrointestinal bleeding, and vascular catheter-related infection is reviewed and common preventive treatments are evaluated to provide evidence-based recommendations for prevention.
44 citations
42 citations
TL;DR: A novel method for measuring osmotically driven water permeability across microvessels in intact lung is established and the high Pf, low Ea, and mercurial inhibition indicate the involvement of molecular water channels in water transport across the lung endothelium.
01 Nov 1998
TL;DR: It may be possible to increase the rate of alveolar fluid clearance and hence the resolution of pulmonary edema in some patients, using aerosolized beta-adrenergic agonist therapy.
Abstract: New evidence indicates that alveolar fluid clearance is driven by active sodium transport across the alveolar epithelium. Several in vivo as well as some in vitro studies indicate that vectorial sodium transport drives fluid clearance across the alveolar epithelium. This transport process can be upregulated by both catecholamine-dependent and catecholamine-independent mechanisms. Water transport appears to move across the alveolar epithelium primarily via transcellular water channels, recently termed aquaporins. Under some conditions, net alveolar fluid clearance continues even in the presence of acute lung injury. It is now possible to study the rate and mechanisms of alveolar fluid clearance in patients with either hydrostatic or increased permeability pulmonary edema. In addition, it may be possible to increase the rate of alveolar fluid clearance and hence the resolution of pulmonary edema in some patients, using aerosolized beta-adrenergic agonist therapy.
TL;DR: Results indicate that a KATP channel opener can effect potassium transport and net vectorial fluid movement across the human alveolar epithelium.
Abstract: Since the effect of an ATP-sensitive potassium channel (KATP channel) opener on the function of alveolar epithelial cells is unknown, the effect of YM934, a newly synthesized KATP channel opener, on potassium influx into the alveolar spaces and alveolar fluid clearance was determined in the resected human lung. An isosmolar albumin solution with a low potassium concentration was instilled into the distal airspaces of resected human lungs. Alveolar fluid clearance was measured by the progressive increase in alveolar protein concentration. Net potassium transport was measured by the change in potassium concentration and alveolar fluid volume. YM934 (10(-4) M) increased net influx of potassium by 140% into the alveolar spaces and also increased alveolar fluid clearance by 60% in the experiments with a potassium concentration of 0.3 mEq/1. Glibenclamide (10(-4) M), a KATP channel blocker, inhibited the YM934-increased influx of potassium transport and the increase in alveolar fluid clearance. Also amiloride (10(-5) M), an inhibitors of apical sodium uptake, blocked the YM934 stimulated increase in net alveolar fluid clearance. These results indicate that a KATP channel opener can effect potassium transport and net vectorial fluid movement across the human alveolar epithelium.
TL;DR: Quantitative densitometry indicated that the single-channel water permeability of T1 alpha is under 2 x 10(-16) cm3/s, suggesting that T1alpha is not involved in the high transalveolar water permeable in intact lung.
Abstract: T1alpha is a protein of unknown function that is expressed at the plasma membrane in epithelia involved in fluid transport, including type I alveolar epithelial cells, choroid plexus, and ciliary epithelium. The purpose of this study was to test the hypothesis that T1alpha functions as a water channel or a regulator of aquaporin-type water channels that are coexpressed with T1alpha. Two complementary DNAs (cDNAs) (hT1alpha-1 and hT1alpha-2) encoding human isoforms of T1alpha were cloned by homology to the rat T1alpha coding sequence. The cDNAs encoded 164 (hT1alpha-1) and 162 (hT1alpha-2) amino acid proteins with high homology to rat T1alpha in a putative membrane-spanning domain. hT1alpha-1 transcripts of 2. 6 and 1.4 kb were detected in human lung, heart, and skeletal muscle, and a single hT1alpha-2 transcript of 1.2 kb was detected in human lung. Rat and mouse T1alpha were isolated by reverse transcription-polymerase chain reaction and confirmed by DNA sequence analysis. Expression of mouse, rat, and human T1alpha isoforms in Xenopus oocytes did not increase osmotic water permeability (Pf) above that in water-injected oocytes, nor was there an effect of protein kinase A or C activation; Pf was increased > 10-fold in positive control oocytes expressing aquaporin (AQP)1 or AQP5. Coexpression of AQP1 or AQP5 with excess T1alpha gave Pf not different from that in oocytes expressing AQP1 or AQP5 alone. Oocyte plasma membrane localization of epitope-tagged T1alpha protein was confirmed and quantified by immunoprecipitation of microdissected plasma membranes. Quantitative densitometry indicated that the single-channel water permeability of T1alpha is under 2 x 10(-16) cm3/s, suggesting that T1alpha is not involved in the high transalveolar water permeability in intact lung. The cloning of hT1alpha isoforms may permit the development of an assay of type I cell antigen in airspace fluid as a marker of human lung injury.
TL;DR: The Round Table on Acute Lung Injury proved a stimulating forum for the interchange of ideas regarding the state of the field and afforded many opportunities for scientific interaction — both during and outside the formal program.
Journal Article•
Journal Article•
01 Jan 1998
TL;DR: This chapter focuses on the mechanisms of salt and water transport across alveolar and distal airway epithelium of the adult lung, including evidence for active sodium transport as a mechanism for regulating in vivoAlveolar fluid clearance.
Abstract: This chapter focuses on the mechanisms of salt and water transport across alveolar and distal airway epithelium of the adult lung. The first section presents evidence for active sodium transport as a mechanism for regulating in vivo alveolar fluid clearance, including a discussion of catecholamine and non-catecholamine dependent mechanisms for stimulating fluid transport. The second section reviews new evidence for involvement of transcellular water channels in alveolar and distal airway fluid transport, and the third section describes how the normal capacity of the alveolar epithelial barrier to transport salt and water is altered by exposure to clinically relevant pathological conditions).
01 Jan 1998
TL;DR: The pathogenetic mechanisms of acute lung injury have been examined in many clinical studies and sensitive and specific biologic markers may provide new insights into the pathogenesis of clinical lung injury.
Abstract: The pathogenetic mechanisms of acute lung injury have been examined in many clinical studies. There are at least three good reasons to search for sensitive and specific biologic markers of clinical acute lung injury (Pittet et al., 1997). First, these markers may improve the prediction of acute lung injury in high-risk clinical conditions such as sepsis, pneumonia, severe trauma, and following aspiration of gastric contents. Secondly, these biologic markers may provide new insights into the pathogenesis of clinical lung injury. Third, the biologic markers may help to predict the outcome of patients once clinical acute lung injury has developed.