Accumulating data support the view that sepsis is associated with an acquired intrinsic derangement in the ability of cells to consume O 2, a phenomenon that has been termed "cytopathic hypoxia." We sought to use an in vitro "reductionist" model system using cultured cells stimulated with proinflammatory cytokines to test the hypothesis that cytopathic hypoxia is mediated, at least in part, by depletion of intracellular levels of NAD ϩ / NADH secondary to activation of the nuclear enzyme poly-(ADP-ribose) polymerase (PARP). We measured O2 consumption by Caco-2 enterocytes growing on microcarrier beads after cells were incubated for 24 h under control conditions or with cytomix, a mixture of tumor necrosis factor-␣, interleukin-1␤, and interferon-␥. Immunostimulated cells consumed O2 at about one-half the rate of control cells, but this effect was largely prevented if any one of the following pharmacological agents was present during the period of incubation with cytomix: 4,5-dihydroxy-1,3-benzene disulfonic acid, a superoxide radical anion scavenger; 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a nitric oxide scavenger; 5,10,15,20-HCl, a chemically dissimilar and more potent PARP inhibitor. The decrease in O 2 uptake induced by cytomix was associated with decreased cellular levels of NAD ϩ /NADH. The decrease in cellular NAD ϩ /NADH content and the decrease in O2 uptake induced by cytomix were completely abrogated if liposome-encapsulated NAD ϩ was added to the cultures during immunostimulation. Empty liposomes also increased O2 uptake by immunostimulated Caco-2 cells, but much less effectively than liposomes containing NAD ϩ . These data are consistent with the view that enterocytes exposed to proinflammatory cytokines consume less O2 due to NAD ϩ /NADH depletion secondary to activation of PARP by ONOO Ϫ or other oxidants.poly(ADP-ribose) polymerase; nitric oxide; peroxynitrite; enterocyte; epithelium; intestinal ACCUMULATING DATA SUPPORT the view that sepsis is associated with an acquired intrinsic derangement in the ability of cells to consume O 2 . This phenomenon has been termed "cytopathic hypoxia" (15). Direct and indirect evidence exists for the development of cytopathic hypoxia in sepsis (or related inflammatory conditions, such as endotoxemia) in experimental animals. For example, tissue PO 2 has been shown to increase in rats (33) and pigs (42) infused with purified lipopolysaccharide (LPS) and also in human patients with septic shock (5). In an indirect way, these data suggest that the ability of cells to extract O 2 from arterial blood is impaired in these conditions, which are associated with systemic inflammation. More direct evidence comes from a study performed by Kantrow et al. (22), where it was shown that the rate of O 2 consumption by hepatocytes isolated from septic rats was less than that by liver cells from control rats. More recently, King et al. (25), working in our laboratory, showed that ex vivo O 2 consumption by ileal mucosa was decreased (relative to the norm...

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Purpose:To describe the epidemiology of the acute respiratory distress syndrome (ARDS) in a Brazilian ICU.Methods: This prospective observational, non-interventional study, included all consecutive patients with ARDS criteria [1] admitted in the ICU of a Brazilian tertiary hospital, between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at ICU admission and at ARDS diagnosis, cause of ARDS, presence of AIDS, cancer and immunosuppression, occurrence of barotrauma, performance of traqueostomy, mortality, duration of mechanical ventilation (MV), length of stay (LOS) in ICU and in hospital. The lung injury score (LIS) [2] was used to quantify the degree of pulmonary injury in the first week of ARDS. Results:There was 2182 patients (P) admitted in ICU during the study period, of whom 141 (6.46%) had ARDS criteria. Seventy-six (54%) were men, the mean age was 46 ± 18 years, APACHE II 18 ± 7 and 19 ± 7 at admission and at ARDS diagnosis, respectively. Septic shock accounted for 42% (60 P) of the ARDS causes, sepsis 22% (31 P), diffuse pulmonary infection 16% (23 P), aspiration pneumonia 11% (15 P), non-septic shock 5% (7 P) and others 4% (5 P). Ten percent (14 P) had AIDS, 30% (43 P) cancer and 25% (36 P) immunosuppression. All patients were mechanically ventilated with Tidal Volume between 4 and 8 ml/kg. Only 3.5% (5 P) had barotrauma and 10% (14 P) performed traqueostomy. Mortality rate was 79% in the ICU. The patients required 12 ± 10 days on MV, ranging from 1 to 55 days. The LOS in ICU and hospital was 14 ± 13 (1-69) days and 28 ± 32 (1-325) days, respectively. There was a time delay of 3.7 ± 4.5 days between admission in ICU and the onset of ARDS. The Murray score (mean ± SD) was 3.2 ± 0.4, 3 ± 0.5, 3 ± 0.5, 2.9 ± 0.6, 2.8 ± 0.7, 2.7 ± 0.7 and 2.6 ± 0.8 in the first 7 days, respectively.Conclusions: ARDS in our hospital has a similar incidence of reports in the USA and Europe. There was a higher mortality, which could be explained by a high incidence of infection causes of ARDS, mainly septic shock, and elevated combined occurrence of AIDS, cancer and immunosuppression, along the degree of LIS. The incidence of barotrauma was low, as a consequence of the current mechanical ventilation strategies. References:1. Bernard GR, Artigas A, Brigham KL, et al.: Am Respir Crit Care Med 1994 P2Role of multiple organ dysfunction syndrome in ARDS mortality FS Dias, N Almeida, IC Wawrzeniack, PB Nery Hospital São Lucas da PUCRS, Av. Ipiranga 6690, RS, Brazil Purpose: To correlate the occurrence and level of organ dysfunction in ARDS with mortality. Methods:This cohort study includes all consecutive patients with ARDS criteria [1] admitted in the ICU between January 1997 and September 2001. Were collected in a prospective fashion the following variables: age, gender, APACHE II score at the ARDS diagnosis, the occurrence of organ dysfunction determined by the multiple organ dysfunction syndrome (MODS) [2] in the first week, and mortality in ...

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