Invisible Parasites and Their Implications for Coexisting Water Fleas.

The top-down effects of consumers, such as predators, are known to affect abundances, size structure, and species composition in aquatic ecosystems. Parasites are also important in shaping the ecology of free-living species; however, their effects are often overlooked because parasites can be difficult to detect. Parasites can be particularly challenging to observe in zooplankton hosts because of their small size and ephemeral infection periods. To overcome these challenges, we used a quarantine approach combined with high-magnification microscopy to increase detection of parasites of the tropical Cladoceran, Ceriodaphnia cornuta, in Lake Gatun, Panamá. Using this approach, we were able to demonstrate that competing morphs of Ceriodaphnia experience differential rates of infection, where the subordinate competitor suffered higher parasite prevalence than did the dominant morph. Predation by fishes on the dominant morph is considered the principal mechanism for their coexistence, but we hypothesize that parasites may also play a role in maintaining morphotype diversity of Ceriodaphnia.

Host density increases parasite recruitment but decreases host risk in a snail-trematode system.

Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail-density-trematode-prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective-stage input, but this was significant only for miracidium-transmitted species. A model parameterized with our experimental results and snail densities from 524 field transects estimated that safety in numbers, when combined with patchy host density, halved per capita infection risk in this snail population. We conclude that, depending on transmission mode, host density can enhance parasite recruitment and reduce per capita infection risk.

Long-term outcomes of patients after acute respiratory distress syndrome: hard work for nothing?

Acute respiratory distress syndrome (ARDS) is a common syndrome that can impose significant health burdens on individuals and the health care systems that serve them. Patients who are treated for this condition in the acute setting often face long-term physical and psychological complications that result from their prolonged hospitalization. While there is reasonable evidence for the use of conventional ventilation strategies, little is known about the effectiveness of unconventional treatment strategies; moreover, the existing literature does not support routine use of these often expensive interventions. It is difficult to prognosticate the long-term function of an individual patient in the acute setting, and thus it is too early to say that some of the unconventional treatments should be abandoned merely because the existing studies do not demonstrate efficacy. This is complicated by the fact that ARDS is a heterogeneous syndrome with a heterogeneous patient population. Experts in ARDS can reasonably continue to use these interventions (with caution, based on their clinical experience) and should continually evaluate their physiologic effect; however, we must keep in mind that there is no clear evidence as to whether these treatments provide benefit or harm and that continuous, rigorous evaluation is required.

First Report of Pyrenophora seminiperda in Turkey and Greece.

Pyrenophora seminiperda (Brittleb. & D.B. Adam) Shoemaker (anamorph Drechslera campanulata (Lév.) B. Sutton) is a generalist seed pathogen that can cause high mortality in the seed banks of annual and perennial grasses and a minor leaf spot disease. Its current reported distribution is mainly temperate grasslands, deserts, and winter cereal-growing regions in Argentina, Australia, Canada, Egypt, New Zealand, South Africa, and the United States (2). P. seminiperda was originally described in France in the mid-1800s, but there are no recent reports from eastern Europe or Asia (2). In May of 2008, we observed what appeared to be P. seminiperda on seeds from seed bank samples collected in Turkey. Evidence of disease was observed as macroscopic black stromata protruding from the seed. The characteristic club-shaped stromata were collected from a Taeniatherum caput-medusae seed near Pamukkale, Turkey and six Bromus tectorum seeds in Love Valley near Goreme, Turkey. An additional collection from a single undispersed B. tectorum seed was obtained from Perissa, Greece. Identity of the pathogen was tentatively established by evaluating morphological characteristics for nine isolates in V8 agar culture. After 4 days of incubation at 20°C with a 12-h photoperiod, the cultures produced white mycelium. Following wounding, the mycelium produced black, club-shaped stromata (2 to 8 × 0.4 to 0.9 mm) in a radial pattern. These produced branched conidiophores bearing crescent-shaped, multicellular conidia (79 to 125 µm long). These attributes are consistent with those of the anamorph of P. seminiperda as described by Shoemaker (4) and Campbell et al. (1). The teleomorph was not observed. The identity of the isolates as P. seminiperda was confirmed with ribosomal DNA internal transcribed spacer (ITS) genetic sequencing analysis. ITS sequences obtained were identical to sequences for North American haplotypes of this species. Four of the Love Valley isolates, (representative isolate: GQ168725, BPI 879142, NRRL 54032) matched the HTA haplotype (GQ168724), while the other four (representative isolate: GQ168736, BPI 879143, NRRL 54033) matched the HTJ haplotype (GQ168735). The isolate from Perissa, Greece (GQ168728, BPI 879144, NRRL 54034) matched the HTC haplotype (GQ168727). Pathogenicity of several Love Valley isolates was confirmed by producing conidia in culture, dusting nondormant B. tectorum seeds with 0.003 g of conidial inoculum per 50 seeds, and incubating for 14 days at 10/20°C with a 12-h photoperiod. Stromata developed on >90% of inoculated seeds and mortality as high as 34% was observed. Morphological similarities combined with ITS sequence data provide conclusive evidence that P. seminiperda occurs in Turkey and Greece. The discovery of this pathogen in these countries indicates that it may be widespread in Eurasia and that it could have arrived in North America on seeds of B. tectorum (3) rather than representing a novel pathogen for this important weed in its North American range. References: (1) M. A. Campbell et al. Plant Pathol. 52:448, 2003. (2) R. W. Medd et al. Australas. Plant Pathol. 32:539, 2003. (3) S. E. Meyer et al. Can J. Plant Pathol. 30:525, 2008. (4) R. A. Shoemaker. Can. J. Bot. 44:1451, 1966.

Practising evidence-based medicine: the design and implementation of a multidisciplinary team-driven extubation protocol.

BACKGROUND: Evidence from recent literature shows that protocol-directed extubation is a useful approach to liberate patients from mechanical ventilation (MV). However, research evidence does not necessarily provide guidance on how to implement changes in individual intensive care units (ICUs). We conducted the present study to determine whether such an evidence-based strategy can be implemented safely and effectively using a multidisciplinary team (MDT) approach. METHOD: We designed a MDT-driven extubation protocol. Multiple meetings were held to encourage constructive criticism of the design by attending physicians, nurses and respiratory care practitioners (RCPs), in order to define a protocol that was evidence based and acceptable to all clinical staff involved in the process of extubation. It was subsequently implemented and evaluated in our medical/ surgical ICU. Outcomes included response of the MDT to the initiative, duration of MV and stay in the ICU, as well as reintubation rate. RESULTS: The MDT responded favourably to the design and implementation of this MDT-driven extubation protocol, because it provided greater autonomy to the staff. Outcomes reported in the literature and in the historical control group were compared with those in the protocol group, and indicated similar durations of MV and ICU stay, as well as reintubation rates. No adverse events were documented. CONCLUSION: An MDT approach to protocol-directed extubation can be implemented safely and effectively in a multidisciplinary ICU. Such an effort is viewed favourably by the entire team and is useful in enhancing team building.

Handheld computers in critical care.

BACKGROUND: Computing technology has the potential to improve health care management but is often underutilized. Handheld computers are versatile and relatively inexpensive, bringing the benefits of computers to the bedside. We evaluated the role of this technology for managing patient data and accessing medical reference information, in an academic intensive-care unit (ICU). METHODS: Palm III series handheld devices were given to the ICU team, each installed with medical reference information, schedules, and contact numbers. Users underwent a 1-hour training session introducing the hardware and software. Various patient data management applications were assessed during the study period. Qualitative assessment of the benefits, drawbacks, and suggestions was performed by an independent company, using focus groups. An objective comparison between a paper and electronic handheld textbook was achieved using clinical scenario tests. RESULTS: During the 6-month study period, the 20 physicians and 6 paramedical staff who used the handheld devices found them convenient and functional but suggested more comprehensive training and improved search facilities. Comparison of the handheld computer with the conventional paper text revealed equivalence. Access to computerized patient information improved communication, particularly with regard to long-stay patients, but changes to the software and the process were suggested. CONCLUSIONS: The introduction of this technology was well received despite differences in users' familiarity with the devices. Handheld computers have potential in the ICU, but systems need to be developed specifically for the critical-care environment.

Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome.

OBJECTIVE: To evaluate the safety and efficacy of high-frequency oscillatory ventilation (HFOV) in adult patients with the acute respiratory distress syndrome (ARDS) and oxygenation failure. DESIGN: Prospective, clinical study. SETTING: Intensive care and burn units of two university teaching hospitals. PATIENTS: Twenty-four adults (10 females, 14 males, aged 48.5 +/- 15.2 yrs, Acute Physiology and Chronic Health Evaluation II score 21.5 +/- 6.9) with ARDS (lung injury score 3.4 +/- 0.6, Pao2/Fio2 98.8 +/- 39.0 mm Hg, and oxygenation index 32.5 +/- 19.6) who met one of the following criteria: Pao2 < or =65 mm Hg with Fio2 > or =0.6, or plateau pressure > or =35 cm H2O. INTERVENTIONS: HFOV was initiated in patients with ARDS after varying periods of conventional ventilation (CV). Mean airway pressure (Paw) was initially set 5 cm H2O greater than Paw during CV, and was subsequently titrated to maintain oxygen saturation between 88% and 93% and Fio2 < or =0.60. MEASUREMENTS AND MAIN RESULTS: Fio2, Paw, pressure amplitude of oscillation, frequency, blood pressure, heart rate, and arterial blood gases were monitored during the transition from CV to HFOV, and every 8 hrs thereafter for 72 hrs. In 16 patients who had pulmonary artery catheters in place, cardiac hemodynamics were recorded at the same time intervals. Throughout the HFOV trial, Paw was significantly higher than that applied during CV. Within 8 hrs of HFOV application, and for the duration of the trial, Fio2 and Paco2 were lower, and Pao2/Fio2 was higher than baseline values during CV. Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure (at 8 and 40 hrs) and central venous pressure (at 16 and 40 hrs), and a reduction in cardiac output throughout the course of the study. There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV. Complications occurring during HFOV included pneumothorax in two patients and desiccation of secretions in one patient. Survival at 30 days was 33%, with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors (1.6 +/- 1.2 vs. 7.8 +/- 5.8 days; p =.001). CONCLUSIONS: These findings suggest that HFOV has beneficial effects on oxygenation and ventilation, and may be a safe and effective rescue therapy for patients with severe oxygenation failure. In addition, early institution of HFOV may be advantageous.

Agreement between alternative classifications of acute respiratory distress syndrome.

To examine the agreement between two classifications of acute respiratory distress syndrome (ARDS) that are used interchangeably in clinical practice and clinical research, we classified 118 patients taking part in a randomized trial with respect to the presence of ARDS using the North American-European Consensus Committee (NAECC) and the Lung Injury Severity Score (LISS) criteria. The incidence of ARDS using NAECC criteria was 55.1% (95% confidence interval, 46.1% to 64.1%), and using the LISS criteria 61.9% (95% confidence interval, 53.1% to 70.6%). The p value on the difference between these proportions was 0.07. Raw agreement, chance-corrected agreement (kappa), and chance-independent agreement (phi) on the study occurrence of ARDS using the two classifications were, respectively, 0.73 (95% CI, 0.65 to 0.81), 0.46 (95% CI, 0.32 to 0.61), and 0.63 (95% CI, 0.41 to 0.79). No single component of either index contributed to disagreement to an appreciably greater extent than other components. Baseline characteristics and outcomes were similar among patients who developed ARDS according to either classification. We conclude that NAECC and LISS classifications resulted in similar estimates of the incidence of ARDS in this clinical trial, though patients were frequently classified as having ARDS with only one model. These discordant classifications had no prognostic importance.

The use of high-frequency oscillatory ventilation in adults with acute lung injury.

The use of HFOV in adults is still in its infancy. There is, however, much promise to support further study of this ventilatory modality. Rescue case series have shown that HFOV is effective in improving gas exchange and appears safe in this group of extremely ill patients. In addition, as evidence continues to mount regarding the importance of VILI and its mechanisms, HFOV provides a theoretically attractive alternative to conventional lung-protective ventilatory modes. When HFOV is used in adults, it should be in conjunction with an effort to recruit atelectatic lung units by employing higher mean airway pressures and weaning FIO2 before P(AW). HFOV could be used as one of a number of new therapies for the patient failing to oxygenate on CMV. Its routine use to prevent VILI cannot be recommended at this time, as no data are available. Further clinical studies potentially leading to a large randomized controlled trial of HFOV versus best conventional therapy appear worth pursuing.

Sleep in critically ill patients requiring mechanical ventilation.

STUDY OBJECTIVES: To objectively measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population. DESIGN: Prospective cohort analysis. SETTING: University teaching hospital medical-surgical ICU. PATIENTS: Twenty critically ill (APACHE II [acute physiology and chronic health evaluation II] acute physiology score [APS], 10 +/- 5), mechanically ventilated adults (male 12, female 8, age 62 +/- 15 years) with mild to moderate acute lung injury (lung injury score, 1.8 +/- 0.9) 10 +/- 7 days after admission to the ICU. MEASUREMENTS AND RESULTS: Patients were divided into three groups based on 24-h polysomnography (PSG) findings. No patient demonstrated normal sleep. In the "disrupted sleep" group (n = 8), electrophysiologic sleep was identified and was distributed throughout the day (6:00 AM to 10:00 PM; 4.0 +/- 2.9 h) and night (10:00 PM to 6:00 AM; 3.0 +/- 1.9 h) with equivalent proportions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Nocturnal sleep efficiency was severely reduced (38 +/- 24%) with an increased proportion of stage 1 NREM sleep (40 +/- 28% total sleep time [TST]) and a reduced proportion of REM sleep (10 +/- 14% TST). Severe sleep fragmentation was reflected by a high frequency of arousals (20 +/- 17/h) and awakenings (22 +/- 25/h). Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients. These were classified either as "atypical sleep" (n = 5), characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep, or "coma" (n = 7), characterized by > 50% delta or theta EEG activity with (n = 5) and without (n = 2) evidence of EEG activation either spontaneously or in response to deep painful stimuli. The combined atypical sleep and coma groups had a higher APS (13 +/- 4 vs 6 +/- 4) and higher doses of sedative medications than the disrupted sleep group. CONCLUSION: Sleep, as it is conventionally measured, was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted. We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population.

Interobserver variation in interpreting chest radiographs for the diagnosis of acute respiratory distress syndrome.

To measure the reliability of chest radiographic diagnosis of acute respiratory distress syndrome (ARDS) we conducted an observer agreement study in which two of eight intensivists and a radiologist, blinded to one another's interpretation, reviewed 778 radiographs from 99 critically ill patients. One intensivist and a radiologist participated in pilot training. Raters made a global rating of the presence of ARDS on the basis of diffuse bilateral infiltrates. We assessed interobserver agreement in a pairwise fashion. For rater pairings in which one rater had not participated in the consensus process we found moderate levels of raw (0.68 to 0.80), chance-corrected (kappa 0.38 to 0.55), and chance-independent (Phi 0. 53 to 0.75) agreement. The pair of raters who participated in consensus training achieved excellent to almost perfect raw (0.88 to 0.94), chance-corrected (kappa 0.72 to 0.88), and chance-independent (Phi 0.74 to 0.89) agreement. We conclude that intensivists without formal consensus training can achieve moderate levels of agreement. Consensus training is necessary to achieve the substantial or almost perfect levels of agreement optimal for the conduct of clinical trials.

Inhaled nitric oxide does not alter pulmonary or cardiac effects of fat embolism in dogs after cemented arthroplasty.

PURPOSE: We examined the effect of inhaled nitric oxide (NO) on the acute pulmonary hypertension and right ventricular (RV) dilation after fat embolism. METHODS: A bilateral cemented arthroplasty (BCA), created fat embolism in 20 dogs. In Part A, 12 dogs were randomized to an NO group (n=6, inhaled NO 40 ppm before BCA and throughout the study) or a control group (n=6). In Part B, a third group of dogs (n=8) were given NO 20-40 ppm 2-3 min after BCA when pulmonary artery pressure (PAP) increased. Transesophageal echocardiography (TEE) and invasive hemodynamic monitoring evaluated the hemodynamic response to BCA. Postmortem, quantitative morphometry was used to estimate the number of fat emboli and diameter of lung vessel occluded by fat. RESULTS: Part A: The increase in PAP in the NO group (16 +/- 1 to 34 +/- 9 mmHg) within three minutes of BCA was not different from that in the control group (14 +/- 4 to 35 +/- 9 mmHg). Within three minutes of BCA, TEE demonstrated RV dilation in all groups (P < 0.05) but there was no difference in the change in RV area in the NO and control groups. When NO was given after BCA, no difference in PAP or RV dilation was noted from that in the control group. There were no differences, at post mortem, between the groups in the diameter of lung vessel occluded by fat CONCLUSION: Whether given before the embolic insult or two to three minutes after the onset of pulmonary hypertension, inhaled NO did not attenuate the acute pulmonary hypertension or RV dilation after cemented arthroplasty.

Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma.

OBJECTIVES: To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury. DESIGN: Prospective blinded cohort analysis. SETTING: Three university-affiliated medical-surgical intensive care units. PATIENTS: A total of 28 survivors of acute lung injury, 1-2 yrs after diagnosis, from a multicenter prospective randomized controlled trial comparing pressure (peak inflation pressure < or =30 cm H2O) and volume (tidal volume < or =8 mL/kg) limited ventilation to a conventional (peak inflation pressure < or =50 cm H2O, tidal volume 10-15 mL/kg) ventilation strategy. MEASUREMENTS AND MAIN RESULTS: Physicians blinded as to treatment group evaluated 20 of 28 survivors (treatment group, 7; control group, 13). Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups (treatment group, 373+/-171 m vs. control group, 375+/-129 m; p = .84). Pulmonary function testing showed reduced diffusing capacity (treatment group, 64+/-29% predicted vs. control group, 74+/-14% predicted; p = .68) and normal volumes, flows, and blood gases. Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Questionnaire were worse for patients in the treatment group compared with the control group (Emotional Function 3.8+/-1.4 vs. 5.1+/-0.08; p = .05, Mastery 4.7+/-1.7 vs. 6.2+/-0.8; p = .03). There were no between-group differences in the scores of the Spitzer Quality of Life Index (a generic Health Related Quality of Life instrument), although they were reduced (7.5+/-1.9) and comparable to patients with chronic disease. CONCLUSIONS: We found that 1-2 yrs after the onset of their illness, survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases. We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury.

ARDS in patients with thermal injury.

OBJECTIVE: To determine the time to onset of the adult respiratory distress syndrome (ARDS) in patients with thermal injury requiring mechanical ventilation. Secondarily, to consider the burn-related risk factors, demographics, incidence, and mortality for ARDS in this population. DESIGN: Retrospective chart review; ARDS defined according to the American-European Consensus Conference and the Lung Injury Severity Score definitions. SETTING: Regional, tertiary referral, adult burn unit in a university teaching hospital. PATIENTS AND PARTICIPANTS: Patients with thermal injury requiring mechanical ventilation, admitted between 1 January 1991 and 28 February 1995. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of 469 consecutive admissions, 126 (26.9%) received intubation and mechanical ventilation. ARDS was defined according to the American-European Consensus and Lung Injury Severity Score (score > 2.5) definitions. The mean time to onset of ARDS from admission to the burn unit was 6.9 +/- 5.2 and 8.2 +/- 10.7 days when defined by the American-European Consensus and Lung Injury Severity Score definitions respectively (p = 0.41). Of the intubated patients, 53.6 and 45.2% developed ARDS according to the American-European Consensus and Lung Injury Severity Score definitions, respectively (p = 0.19). Using multivariate logistic analysis, only age proved to be an independent risk factor for the development of ARDS (p = 0.03), although there was a trend toward an increased incidence of inhalation injury in patients with ARDS. Mortality was not significantly greater (41.8 vs 32.2%) in those with ARDS compared to those without (p = 0.27). CONCLUSIONS: According to the American-European Consensus Conference and the Lung Injury Severity Score definitions, ARDS is common in the adult burn population and has a delayed onset compared to most critical care populations. We found age to be a major predisposing factor for ARDS.

Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation.

OBJECTIVES: Increases in exhaled nitric oxide have been demonstrated to originate from the lungs of rats after septic lung injury. The aim of this study was to investigate whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) would prevent lipopolysaccharide (LPS)-induced increases in exhaled nitric oxide and whether this would have an effect on septic lung inflammation. DESIGN: Prospective, randomized, placebo-controlled animal laboratory investigation. SETTING: University laboratory. SUBJECTS: Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 27). INTERVENTIONS: Rats were mechanically ventilated with air filtered to remove nitric oxide (expiratory rate 40 breaths/min, tidal volume 3 mL, positive end-expiratory pressure 0, FIO2 0.21). They were then randomized to receive intravenous injections of either L-NAME (25 mg/kg/hr x 4 hrs) (n = 11) or saline (n = 10). Both groups were again randomized to receive either LPS (Salmonella typhosa: 20 mg/kg i.v. x 1 dose) or an equal volume of saline 5 mins later. Thereafter, exhaled gas was collected in polyethylene bags for measurements of nitric oxide concentration. After 4 hrs, the rats were killed and the lungs were preserved and examined histologically. To examine the effect of L-NAME and LPS on mean arterial blood pressure, six additional rats underwent the same ventilation protocol with cannulation of the right internal carotid artery so that systemic arterial pressures could be measured. MEASUREMENTS AND MAIN RESULTS: Exhaled gas was collected and measurements of NO concentrations were made using chemiluminescence every 20 mins for 240 mins during ventilation. A total lung injury score was calculated by determining the extent of cellular infiltrate, exudate and hemorrhage. Mean arterial pressure was recorded every 5 mins for 20 mins and then at 20-min periods for 120 mins. Exhaled nitric oxide concentrations increased in all the LPS-treated rats that did not receive L-NAME by 120 mins; a plateau was reached by 190 mins that was approximately 4 times greater than control rats not treated with LPS (p < .001). In contrast, rats treated with L-NAME and LPS did not show an increase in exhaled NO. Administration of L-NAME induced a 10-min nonsustained increase in mean arterial pressure in two rats treated with L-NAME followed by LPS. This increase in mean arterial pressure was not seen in two placebo and two LPS-treated rats that did not receive L-NAME. Lung inflammation was significantly worse in the two groups of rats which received LPS compared with the two that did not. L-NAME did not cause lung inflammation in rats that did not receive LPS; however, LPS-treated rats that received L-NAME had more inflammatory interstitial infiltrate (p < .05) and a trend toward worse lung injury than did LPS-treated rats that did not receive L-NAME. CONCLUSION: We conclude that L-NAME can inhibit the increase in exhaled NO from the lungs of septic rats, but that this inhibition does not reduce lung inflammation, and may worsen it.