Lung water assessment: from gravimetry to wearables.

Several techniques are now available to detect and quantify pulmonary edema, from the laboratory postmortem method (gravimetry) to non-invasive wearable sensors. In critically ill patients with adult respiratory distress syndrome (ARDS), computed tomography scans are often performed to visualize lung lesions and quantify lung aeration, but their value seems somewhat limited to quantify pulmonary edema on a routine basis and of course to track changes with therapy. In this context, transpulmonary thermodilution is a convenient technique. It is invasive but most patients with ARDS have a central line and an arterial catheter in place. In addition to extravascular lung water measurements, transpulmonary thermodilution enables the measurement of hemodynamic variables that are useful to guide fluid and diuretic therapy. Echo probes are about to replace the stethoscope in our pocket and, if B lines (aka comet tails) do not allow a real quantification of pulmonary edema, they are useful to detect an increase in lung water. Finally, wireless and wearable sensors are now available to monitor patients on hospital wards and beyond (home monitoring). They should enable the detection of pulmonary congestion at a very early stage, and if combined with a proactive therapeutic strategy, have potential to improve outcome.

Accuracy of ultrasound B-lines score and E/Ea ratio to estimate extravascular lung water and its variations in patients with acute respiratory distress syndrome.

Extravascular lung water (EVLW) could increase by permeability pulmonary oedema, cardiogenic oedema, or both. Transthoracic echocardiography examination of a patient allows quantifying B-lines, originating from water-thickened interlobular septa, and the E/Ea ratio, related to pulmonary capillary wedge pressure. The aim of our study was to assess the correlation and the trending ability between EVLW measured by transpulmonary thermodilution and the B-lines score or the E/Ea ratio in patients with ARDS. Twenty-six intensive care unit patients were prospectively included. B-lines score was obtained from four ultrasound zones (anterior and lateral chest on left and right hemithorax). E/Ea was measured from the apical four-chamber view. EVLW was compared with the B-lines score and the E/Ea ratio. A linear mixed effect model was used to take account the repeated measurements. A p value<0.05 was considered significant. A total of 73 measurements were collected. The correlation coefficient between EVLW and B-lines score was 0.66 (EVLW=0.71 B-lines+7.64, R2=0.44, p=0.001), versus 0.31 for E/Ea (p=0.06). The correlation between EVLW changes and B-lines variations was significant (R2=0.26, p<0.01), with a concordance rate of 74%. A B-lines score≥6 had a sensitivity of 82% and a specificity of 77% to predict EVLW>10 ml/kg, with an AUC equal to 0.86 (0.76-0.93). The gray zone approach identified a range of B-lines between four and seven for which EVLW>10 ml/kg could not be predicted reliably. The correlation between ultrasound B-lines and EVLW was significant, but the B-lines score was not able to track EVLW changes reliably.

Pulmonary fluid flow challenges for experimental and mathematical modeling.

Modeling the flow of fluid in the lungs, even under baseline healthy conditions, presents many challenges. The complex rheology of the fluids, interaction between fluids and structures, and complicated multi-scale geometry all add to the complexity of the problem. We provide a brief overview of approaches used to model three aspects of pulmonary fluid and flow: the surfactant layer in the deep branches of the lung, the mucus layer in the upper airway branches, and closure/reopening of the airway. We discuss models of each aspect, the potential to capture biological and therapeutic information, and open questions worthy of further investigation. We hope to promote multi-disciplinary collaboration by providing insights into mathematical descriptions of fluid-mechanics in the lung and the kinds of predictions these models can make.

Interleukin 27 could be useful in the diagnosis of tuberculous pleural effusions.

BACKGROUND: The diagnosis of tuberculous pleural effusion (TBPE) has some limitations. We studied the efficacy of interleukin-27 (IL-27) in the diagnosis of TBPE. METHODS: We measured IL-27, adenosine deaminase (ADA), ADA-2, interferon-gamma (IFNγ), and the ADA·IL-27 and ADA-2·IL-27 products in all the pleural effusion fluids. The diagnostic yield of IL-27 was evaluated with receiver operating characteristic curves. RESULTS: Of 431 pleural effusions, 70 were tuberculous, 146 were neoplastic, 58 were parapneumonic, 28 were empyemas, 88 were transudates, and 41 were other types. With a cutoff point of 0.55 ng/mL, IL-27 had a sensitivity of 91.4% and a specificity of 85.1%, which were significantly less than ADA, ADA-2, IFNγ, ADA·IL-27, or ADA-2·IL-27. The area under the receiver operating characteristic curve for IL-27 (0.963) was also significantly lower than that for the other markers, except for IFNγ. However, IL-27 improved the sensitivity of ADA and ADA-2 through ADA·IL-27 and ADA-2·IL-27 products (100% for both). CONCLUSIONS: IL-27 is less efficient than ADA and ADA-2 in the diagnosis of TBPE. However, ADA·IL-27 and ADA-2·IL-27 improve the diagnostic sensitivity of ADA and ADA-2, and thus could be useful in situations of high clinical suspicion and low ADA level. A value above the cutoff point of the latter is practically diagnostic of TBPE.

Prediction of quantitative intrathoracic fluid volume to diagnose pulmonary oedema using LabVIEW.

Pulmonary oedema is a life-threatening disease that requires special attention in the area of research and clinical diagnosis. Computer-based techniques are rarely used to quantify the intrathoracic fluid volume (IFV) for diagnostic purposes. This paper discusses a software program developed to detect and diagnose pulmonary oedema using LabVIEW. The software runs on anthropometric dimensions and physiological parameters, mainly transthoracic electrical impedance (TEI). This technique is accurate and faster than existing manual techniques. The LabVIEW software was used to compute the parameters required to quantify IFV. An equation relating per cent control and IFV was obtained. The results of predicted TEI and measured TEI were compared with previously reported data to validate the developed program. It was found that the predicted values of TEI obtained from the computer-based technique were much closer to the measured values of TEI. Six new subjects were enrolled to measure and predict transthoracic impedance and hence to quantify IFV. A similar difference was also observed in the measured and predicted values of TEI for the new subjects.

How important is the measurement of extravascular lung water?

PURPOSE OF REVIEW: Accurate quantification of extravascular lung water is an important issue in the management of patients with pulmonary edema. The single transpulmonary thermal indicator method has been available since the late 1990s. Its simplicity and easy application make it clinically attractive. RECENT FINDINGS: Several experimental studies have confirmed the accuracy of the single transpulmonary thermal indicator technique in comparisons with postmortem gravimetric method. Whereas changes in extravascular lung water of less than 100-200% are undetectable by other clinically applicable methods of lung injury assessment (chest radiograph and oxygenation), the single transpulmonary indicator has proven highly sensitive to small (10-20%) increases and is therefore useful to detect incipient pulmonary edema. In patients with sepsis or acute respiratory distress syndrome, extravascular lung water measurement offers information unobtainable by other means. SUMMARY: Extravascular lung water can be considered a relevant parameter that contributes to rational management of fluid and vasoactive therapy of many critically ill patients and offers a fuller picture of their overall lung function.

[Pulmonary extravascular water in patients with acute respiratory failure].

The purpose of the investigation was to study pulmonary extravascular water levels and pulmonary vascular permeability (PVP) in the pathogenesis of acute respiratory failure (ARF)/acute respiratory distress syndrome (ARDS). Twenty-nine patients with ARF/ARDS and 10 healthy volunteers were examined. Central hemodynamics and oxygen transport were explored, by using a Swan-Ganz catheter. Intrathoracic volemic parameters were studied by the transpulmonary thermodilution technique. PVP was assessed by the pulmonary 67Ga-labelled transferrin leakage index. Plasma colloid osmotic pressure (COP) was measured on an osmometer. In most patients with ARF/ARDS, the pulmonary extravascular water index (PEVWI) was found to be higher (mean 16.9 +/- 1.5 ml/kg). At the same time its value was not greater than 10 ml/kg in 7 (24%) of 29 patients. There were no correlations between PEVWI and PaO2/FiO2 and between pulmonary extravascular water and AaDO2. The PVP index (PVPI) measured by transpulmonary thermodilution was 3.2 +/- 0.2, it being normal in 13 (45%) out of 29 patients. The pulmonary 67Ga-transferrin leakage index was higher in all the patients than in healthy individuals (23.2 +/- 2.9 x 10(-3) vs 5.7 +/- 9.9 x 10(-3)) and correlated with PaO2/FiO2 (r = 0.71; p = 0.01). In patients with ARF/ARDS, COP was lower (19.9 +/- 0.7 mm Hg). There were correlations between COP and PEVWI (r = -0.34; p = 0.01), COP and PVPI (r = -0.40; p = 0.044), COP and PaO2/FiO2 (r = 0.35; p = 0.02). PEVWI correlated with the COP-pulmonary wedge pressure gradient (r = -0.45; p = 0.0024). Hypoxemia correlated with intrapulmonary shunt (Qs/Qt). There was no relationship between Qs/Qt and PEVWI in the group as a whole. According to the ratio of Qs/Qt to PEVWI, the patients were divided into 2 groups. Group 1 comprised 11 patients with the ratio < or = 2; Group 2 included 18 patients with the ratio > or = 2, i.e. with an unproportional shunt enlargement as to the severity of pulmonary edema. A correlation between Qs/Qt and PEVWI was found in both groups: r = 0.82; p = 0.001 with the ratio < or = 2 and r = 0.48; p = 0.04 with the ratio > or = 2. Diverse causes of shunt formation were histologically detected. Thus, pulmonary edema was not identified in 24% of patients with ARF/ARDS. Arterial hypoxemia is associated with the increase in the shunt, but, in a portion of patients, the shunt was caused with atelectasis unassociated with pulmonary edema. Increased pulmonary permeability for transferrin is detectable in ARF/ARDS irrespective the severity of pulmonary edema. The pathogenetic features of lung lesions should be taken into account while choosing a treatment for ARF/ARDS.

Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults.

STUDY OBJECTIVE: To determine the steady-state, extracellular, and intracellular pulmonary disposition of moxifloxacin (MXF), levofloxacin (LEVO), and azithromycin (AZI) relative to that of the plasma over a 24-h dosing interval. DESIGN: Randomized, multicenter, open-label investigation. PATIENTS: Forty-seven older adults (mean [+/- SD] age, 62 +/- 13 years) undergoing diagnostic bronchoscopy. INTERVENTIONS: Oral administration of MXF, 400 mg, LEVO, 500 mg daily for five doses, or AZI, 500 mg for one dose, then 250 mg daily for four doses. BAL and venipuncture were completed at 4, 8, 12, or 24 h following the administration of the last dose. MEASUREMENTS AND RESULTS: Steady-state MXF, LEVO, and AZI concentrations were determined in the plasma, epithelial lining fluid (ELF), and alveolar macrophages (AMs). The concentrations of all three agents were greatest in the AMs followed by the ELF compared to the plasma. Plasma concentrations were similar to those previously reported with these agents. The mean ELF concentrations at 4, 8, 12, and 24 h were as follows: MXF, 11.7 +/- 11.9, 7.8 +/- 5.1, 10.5 +/- 3.7, and 5.7 +/- 6.3 micro g/mL, respectively; LEVO, 15.2 +/- 4.5, 10.2 +/- 6.7, 6.9 +/- 4.4, and 2.9 +/- 1.7 micro g/mL, respectively; and AZI, 0.6 +/- 0.4, 0.7 +/- 0.4, 0.9 +/- 0.5, and 0.9 +/- 0.7 micro g/mL, respectively. The AM concentrations at 4, 8, 12, and 24 h were as follows: MXF, 47.7 +/- 47.6, 123.3 +/- 126.4, 26.2 +/- 19.4, and 32.8 +/- 16.5 micro g/mL, respectively; LEVO, 28.5 +/- 30.2, 26.1 +/- 15.7, 28.3 +/- 12.6, and 8.2 +/- 6.1 micro g/mL, respectively; and AZI, 71.8 +/- 50.1, 73.8 +/- 75.3, 155.9 +/- 81.3, and 205.2 +/- 256.3 micro g/mL, respectively. CONCLUSIONS: The intrapulmonary concentrations of MXF, LEV, and AZI were superior to those obtained in the plasma. The AM concentrations of all agents studied were more than adequate relative to the minimum concentration required to inhibit 90% of the organism population (MIC(90)) of the common intracellular pathogens (< 1 micro g/mL). These data indicate that attainable extracellular concentrations of AZI are insufficient to reliably eradicate Streptococcus pneumoniae, based on the agent's current minimum inhibitory concentration profile, whereas the mean concentrations of MXF and LEVO in the ELF exceed the MIC(90) of the S pneumoniae population. Moreover, MXF concentrations exceeded the S pneumoniae susceptibility breakpoint (1.0 micro g/mL) at all time points, while 2 of 15 concentrations (13%) failed to maintain LEVO concentrations above the breakpoint (2.0 micro g/mL) throughout the dosing interval.

Exhaled breath condensate in children: pearls and pitfalls.

Exhaled breath condensate (EBC) is a rapidly growing field of research in respiratory medicine. Airway inflammation is a central feature of chronic lung diseases, like asthma, cystic fibrosis, bronchopulmonary dysplasia and primary ciliary dyskinesia. EBC may be a useful technique for non-invasive assessment of markers of airway inflammation. The non-invasive character of EBC "inflammometry" and the general lack of appropriate techniques makes it particularly interesting for paediatrics. We provide a detailed update on the methods currently used for EBC collection and measurement of mediators. We emphasize on paediatric data. The apparent simplicity of the EBC method must not be overstated, as numerous methodological pitfalls have yet to overcome. Comparison and interpretation of data on this rapidly growing field of research is mainly hampered by the lack of standardization and the lack of specific high-sensitivity immunochemical or colorimetric assays. The initiative of the European Respiratory Society to institute a task force on this topic is a first step towards a uniform technique of EBC. Meanwhile, when using this technique or when interpreting research data, one should be fully aware of the possible methodological pitfalls.

Alveolar granulocyte colony-stimulating factor and alpha-chemokines in relation to serum levels, pulmonary neutrophilia, and severity of lung injury in ARDS.

OBJECTIVES: To determine granulocyte colony-stimulating factor (G-CSF), epithelial neutrophil-activating peptide (ENA)-78, and interleukin (IL)-8 in BAL fluid (BALF), epithelial lining fluid (ELF), and serum for establishing the concentration gradient of G-CSF, ENA-78, and IL-8 between the blood and the alveolar space in ARDS and acute lung injury (ALI); and to evaluate the relationship of G-CSF, IL-8, and ENA-78 to pulmonary neutrophilia and severity of lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU. PATIENTS: Nineteen patients with ARDS and 10 patients with ALI. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL and blood sampling simultaneously within 12 h and 24 h after onset of ARDS/ALI; G-CSF was detected in BALF in 18 of 19 patients with ARDS, in 7 of 10 patients with ALI, and in all serum samples. G-CSF in BALF and serum was significantly higher in ARDS than in ALI. ENA-78 was detected in BALF in 14 of 19 patients with ARDS, in 8 of 10 patients with ALI, and in serum of all patients. Levels in BALF and serum were not different between ARDS and ALI. IL-8 was detected in all patients; concentrations in BALF in ARDS were significantly higher than in ALI. Concentrations of G-CSF, ENA-78, and IL-8 in ELF were significantly higher than in serum. G-CSF in BALF and serum and IL-8 in BALF correlated positively with pulmonary neutrophilia. G-CSF in serum and IL-8 in BALF correlated negatively with PaO(2)/fraction of inspired oxygen (FIO(2)) ratio. However, ENA-78 did not show a correlation with neutrophil count or with PaO(2)/FIO(2) ratio. CONCLUSIONS: G-CSF may be pathophysiologically important for accumulation and activation of neutrophils in ARDS. Local G-CSF production is the likely driving force for neutrophils rather than elevation of circulating levels. In comparison to ENA-78, IL-8 seems to be the predominant neutrophil chemoattractant in the early phase of ARDS.

A simple method for estimating respiratory solute dilution in exhaled breath condensates.

Exhaled breath condensates have been widely used to detect inflammatory mediators in the fluid that covers airway surfaces of patients with inflammatory lung disorders. This approach is much less invasive than bronchoalveolar lavage, but respiratory droplets are markedly diluted by large and variable amounts of water vapor. We estimated the dilution of respiratory droplets by comparing concentrations of nonvolatile, reference indicators (total nonvolatile cations, urea or conductivity) in 18 normal subjects with normal plasma concentrations by assuming similar concentrations in the respiratory fluid and plasma. The volatile cation, NH4+ (most of which is delivered as NH3 gas from the mouth), represented 93 +/- 3% (SEM) of the condensate cations. More than 99% of the NH4+ was removed by lyophilization, making it possible to use conductivity to estimate total nonvolatile ionic concentrations and facilitating analysis of urea. Conductivity was significantly correlated with electrolyte and urea concentrations. Estimates of dilution based on total cations, conductivity, and urea were not significantly different (cations: 20,472 +/- 2,516; conductivity: 21,019 +/- 2,427; and urea: 18,818 +/- 2,402). These observations suggest that the conductivity of lyophilized samples can be used as an inexpensive, simple, and reliable method for estimating dilution of nonvolatile, hydrophilic mediators in condensates.

Perfusing and ventilating the patient's lungs during bypass ameliorates the increase in extravascular thermal volume after coronary bypass grafting.

BACKGROUND: To test the hypothesis that bilateral extracorporeal circulation (ECC) (Drew technique) ameliorates the increase in extravascular thermal volume (ETV) observed after conventional cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting. METHODS: Thirty-four consecutive patients underwent either bilateral ECC (n = 24, additional cannulation of pulmonary artery and left atrium and lungs perfused and ventilated during bypass) or conventional CPB (n = 10, right atrial and aortic cannulation, lungs statically inflated to 4 mbar (0.41 cm H(2)O) with oxygen, 500 mL/min). Determinations of ETV (thermodye dilution technique) and intraoperative fluid balance were made before surgery, at the end of surgery, and 4 hours thereafter. In addition, interleukin (IL)-8, thromboxane B2 (TxB(2)), and endothelin (ET)-1 concentrations were measured in the right atrium and pulmonary vein at specified time points. RESULTS: Comparisons of ETV made at the start of surgery, after aortic declamping, and after termination of ECC, respectively, revealed an increase from 4.8 +/- 0.2 mL/kg (mean +/- SEM) to 6.7 +/- 0.4 mL/kg, and 6.3 +/- 0.3 mL/kg with conventional CPB but ETV remained unchanged at 5.2 +/- 0.3 mL/kg, 5.1 +/- 0.2 mL/kg, and 4.9 +/- 0.3 mL/kg with bilateral ECC. Priming volume (1,580 +/- 10 mL versus 2,213 +/- 77 mL, p < 0.001) and intraoperative fluid balance (+1,955 +/- 233 mL versus +2,654 +/- 210 mL, p < 0.05) were less with conventional CPB. Concentrations of IL-8, TxB(2), and ET-1 were not different between groups. CONCLUSIONS: Despite a significantly greater prime volume and a more positive intraoperative fluid balance, ETV did not change with bilateral ECC but increased with conventional CPB. Thus, using the patient's lungs as an oxygenator during bypass mitigates the increase in extravascular pulmonary fluid.

Methylene blue reduces pulmonary oedema and cyclo-oxygenase products in endotoxaemic sheep.

The authors recently demonstrated that methylene blue (MB), an inhibitor of the nitric oxide (NO) pathway, reduces the increments in pulmonary capillary pressure, lung lymph flow and protein clearance in endotoxaemic sheep. In the present study, the authors examined whether MB influences pulmonary haemodynamics and accumulation of extravascular lung water (EVLW) by mechanisms other than the NO pathway. Sixteen awake, chronically-instrumented sheep randomly received either an intravenous injection of MB 10 mg x kg(-1) or isotonic saline. Thirty minutes later, all sheep received an intravenous infusion of Escherichia coli endotoxin 1 microg x kg(-1) for 20 min and either an intravenous infusion of MB 2.5 mg x kg(-1) x h(-1) or isotonic saline for 6 h. MB markedly attenuated the endotoxin-induced pulmonary hypertension and right ventricular failure, and reduced the accumulation of EVLW. Moreover, MB reduced the increments in plasma thromboxane B2 and 6-keto-prostaglandin F1alpha, and abolished the febrile response. However, MB had no effect on the changes in circulating neutrophils, serum hyaluronan, and total haemolytic activity of the alternative complement pathway. The authors conclude that in sheep, methylene blue attenuates the endotoxin-induced pulmonary hypertension and oedema, at least in part, by inhibiting the cyclo-oxygenase products of arachidonic acid. This is a novel effect of methylene blue in vivo.

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.

Protective effects of low tidal volume ventilation in a rabbit model of Pseudomonas aeruginosa-induced acute lung injury.

OBJECTIVE: To determine whether low "stretch" mechanical ventilation protects animals from clinical sepsis after direct acute lung injury with Pseudomonas aeruginosa as compared with high "stretch" ventilation. DESIGN: Prospective study. SETTING: Experimental animal laboratory. SUBJECTS: Twenty-seven anesthetized and paralyzed rabbits. INTERVENTIONS: P. aeruginosa (109 colony forming units) was instilled into the right lungs of rabbits that were then ventilated at a tidal volume of either 15 mL/kg (n = 11) or 6 mL/kg (n = 7) for 8 hrs. Control animals were ventilated at a tidal volume of either 15 mL/kg (n = 4) or 6 mL/kg (n = 5) for 8 hrs, but an instillate without bacteria was used. A positive end-expiratory pressure of 3-5 cm H2O was used for all experiments. Radiolabeled albumin was used as a marker of alveolar epithelial permeability. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gas determination, alveolar permeability, wet-to-dry ratios on lungs, and time course of bacteremia were determined. When final values were compared with the values at the beginning of the experiment, there were significant decreases in mean arterial pressure (from 104 +/- 15 to 57 +/- 20 mm Hg), pH (from 7.46 +/- 0.04 to 7.24 +/- 15), Pao2 (from 528 +/- 35 to 129 +/- 104 torr [70.4 +/- 4.7 to 17.2 +/- 13.9 kPa]), and temperature (from 38.2 +/- 1 to 36.2 +/- 1.2 degrees C) in the high tidal volume group, whereas no significant differences were found in the low tidal volume group. Decreased alveolar permeability was shown in the low tidal volume group, as was decreased extravascular lung water in the uninstilled lung in the low tidal volume group (12.7 +/- 2.5 vs. 4.3 +/- 0.45 g H2O/g dry lung). No noteworthy difference was noted in the time course of bacteremia, although there was a trend toward earlier bacteremia in the high tidal volume group. CONCLUSIONS: In our animal model of P. aeruginosa-induced acute lung injury, low tidal volume ventilation was correlated with improved oxygenation, hemodynamic status, and acid-base status as well as decreased alveolar permeability and contralateral extravascular lung water.

Aquaporin channels may modulate ventilator-induced lung injury.

Adult Respiratory Distress Syndrome is a disease with functional lung heterogeneity and thus a ventilator-delivered breath may over-distend non-involved areas. In rats we examined ventilator-delivered tidal volume (TV) breaths of 7 and 20 ml/kg on lung water as evidence of lung injury. We examined the role of aquaporins on ventilator-induced lung injury (VILI) by infusing HgCl(2) which inhibits aquaporins by binding cysteine. Wet to dry lung weight ratio (W/D) as evidence of lung water was 4.47+/-0.1 SEM in controls, 4.6+/-0.1 and 5.5+/-0.2 (P<0.05) in rats ventilated at 7 and 20 ml/kg, respectively. Pulmonary artery pressure (PAP) rose from 23+/-1 to 26+/-1 mmHg (P<0.05, n=7) and cardiac output fell from 104+/-2 to 67+/-3 ml/min (P<0.05) in rats ventilated at 20 ml/kg. Left ventricular end diastolic pressure (n=3) was unchanged. Evans Blue dye, an albumin marker, increased from a control 37+/-11 to 97+/-41 mg/g wet lung in TV 20 rats (P<0.05). HgCl(2) infused slowly by tail vein did not significantly raise PAP, but did increase W/D to 6+/-0.2 (P<0.05) in rats ventilated at 20 ml/kg but not at 7 ml/kg. Equimolar cysteine infusions prevented the HgCl(2) from increasing the W/D above that seen with TV 20 ml/kg. Thus ventilation with TV of 20 ml/kg produced a protein-rich lung edema. Aquaporin channels may have a protective effect in VILI.

Low molecular weight dextran attenuates increase in extravascular lung water caused by ARDS.

We studied the effect of low molecular weight dextran (mean molecular weight 40,000, Dextran 40; LMD) on the accumulation of extravascular lung water (EVLW), and also on hemodynamics and blood gases, in the oleic acid (OA)-injured lung in pentobarbital anesthetized rats. Starting just before the OA injection (0.01 mL/kg via femoral vein), 10% LMD in lactated Ringer's solution was infused throughout the experiment (5 mL/kg/h) instead of lactated Ringer's solution. OA caused acute lung injury leading to decreased oxygenation (PaO2: 87 +/- 11 mmHg versus control group 128 +/- 11) and an increased permeability of the alveolar-capillary membrane, as shown by increases in EVLW (4.89 +/- 0.54 versus control group 4.07 +/- 0.14), and albumin leakage (0.043 +/- 0.015 versus control group 0.010 +/- 0.004). LMD protected against the increase in EVLW (4.14 +/- 0.10) and the hypoxemia (112 +/- 19 mmHg), but it did not reduce the albumin leakage into the alveolar space (0.052 +/- 0.009). These data suggest that LMD may limit the fluid accumulation that is secondary to OA-induced lung injury.

Effects of inhaled nitric oxide and surfactant treatment on lung function and pulmonary hemodynamics in bronchoalveolar-lavage-induced respiratory failure.

Our aim was to study whether inhaled nitric oxide (iNO) moderates respiratory failure induced by bronchoalveolar lavage (BAL) without severe pulmonary hypertension. The following successive treatments, interrupted by 20-30-min rest periods, were given to piglets: iNO (20 ppm for 20 min), exogenous surfactant, iNO, Nomega-nitro-L-arginine methyl ester (L-NAME), and iNO. The controls inhaled NO first after L-NAME. Lung mechanics and hemodynamics were measured serially. The pulmonary to systemic arterial pressure ratio decreased during iNO and tended to increase after its discontinuation. In contrast, the iNO-induced decreases in severity of respiratory failure were not reversible during the rest periods. In a second experiment, iNO/placebo and surfactant containing (3)H-labeled dipalmitoyl phosphatidylcholine were given to rabbits. The surfactant aggregates and the surface activity from postmortem BAL, and extravascular lung water, were studied. Inhaled NO improved the surface activity and increased the large surfactant aggregates. There was no detectable decrease in extravascular lung water. The results suggest that a low dose of iNO has a beneficial effect on the gas exchange that is in part unrelated to its effect on the pulmonary vasculature.