Increase In Extravascular Lung Water Research Articles

The Selective TRPV4 Antagonist GSK2263095A Attenuates High Venous Pressure‐Induced Lung Injury In Murine And Canine Lung

We have shown that the lung permeability response to high venous pressure (HiPv) is abrogated in mice lacking the vanilloid transient receptor potential channel TRPV4. The current study evaluated the efficacy of a novel selective TRPV4 antagonist GSK2263095A in limiting HiPv‐induced lung injury. Lungs isolated from anesthetized C57BL/6 mice or dogs were perfused with buffer/4% albumin or autologous blood, respectively, at constant flow. The filtration coefficient (Kf, an index of endothelial permeability) was measured at baseline (BL) and during 15‐min challenge with 25 or 40 cmH2O HiPv. In mouse lung, 25 cmH2O HiPv increased Kf 4.9‐fold, vs 2.9‐fold in lungs pretreated with 300 nM GSK2263095A (p<0.05). In canine lung, 25 cmH2O HiPv had no significant impact on Kf: 2.0‐ (vehicle) and 1.6‐fold BL (100 nM GSK2263095A). However, 40 cmH2O HiPv increased Kf significantly to 6.1‐fold baseline, an effect attenuated (final Kf 3.0‐ fold. baseline) by pretreatment with 100 nM GSK2263095A (both p<0.05). Further, the TRPV4 antagonist markedly attenuated the HiPv‐induced increase in extravascular lung water (p<0.05) and tended to blunt blood extravasation in canine lung. We conclude that TRPV4 is required for the permeability response to HiPv in both mouse and canine lung, and that the TRPV4 antagonist GSK2263095A is protective against lung injury induced by high pulmonary venous pressure. Supported by GlaxoSmithKline.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57%, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Ultrasound lung comets induced by repeated breath‐hold diving, a study in underwater fishermen

Pulmonary edema has been reported in breath-hold divers during fish-catching diving activity. The present study was designed to detect possible increases in extravascular lung water (EVLW) in underwater fishermen after a competition. Thirty healthy subjects were studied. They participated in two different 5-h fish-catching diving competitions: one organized in the winter (10 subjects) and one organized in the autumn (20 subjects). A questionnaire was used to record underwater activity and note respiratory problems. An increase in EVLW was investigated from the detection of ultrasound lung comets (ULC) by chest ultrasonography. Complementary investigations included echocardiography and pulmonary function testing. An increase in EVLW was detected in three out of 30 underwater fishermen after the competition. No signs of cardiovascular dysfunction were found in the entire population and in divers with an increase in the ULC score. Two divers with raised ULC presented respiratory disorders such as cough or shortness of breath. Impairment in spirometric parameters was recorded in these subjects. An increase in EVLW could be observed after a fish-catching diving competition in three out of 30 underwater fishermen. In two subjects, it was related to respiratory disorders and impairment in pulmonary flow.

Rebuttal from Sheel and McKenzie

POINT:COUNTERPOINTPulmonary edema does/does not occur in human athletes performing heavy sea-level exerciseRebuttal from Sheel and McKenziePublished Online:01 Oct 2010https://doi.org/10.1152/japplphysiol.01353.2009cMoreSectionsPDF (41 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Within the Point presented by Dr. Hopkins (2) several case studies, which have little to do with the debate, are presented as “evidence” of the development of pulmonary edema during heavy sea-level exercise. Anecdotal reports of pulmonary edema induced by emotional stress, sexual intercourse, and exercise at high altitude are all distractions from the central question. Moreover, left ventricular diastolic dysfunction is likely causative in these instances (8) and they represent an entirely different physiological scenario than that of the healthy athlete performing near-maximal exercise at sea level.We disagree with the assertion that the rapid infusion of 20 ml/kg of normal saline into resting humans can be used as supporting evidence for exercise-induced interstitial edema (4). Rather, it produces a nonphysiological situation (i.e., volume overload by ∼1.5 liters), which results in airflow obstruction and changes to airway responsiveness that are not commensurate with the typical exercise response seen in the population being discussed in this debate.Our colleague (2) and others (5) argue that the persistence of V̇A/Q̇ inequality during recovery from heavy exercise supports the idea of an exercise-induced increase in extravascular lung water. Specifically, the logic is that interstitial edema compresses the small airways and blood vessels resulting in a mismatch of V̇A/Q̇. However, this is not direct evidence of edema and should not be interpreted as such. As clearly stated within the concluding statements of the original manuscript by Schaffartzik et al. (5): “It [persistent V̇A/Q̇ mismatch owing to pulmonary interstitial edema] is of course not proof of the hypothesis.” We agree. Alternative explanations for V̇A/Q̇ heterogeneity include changes in airway resistance and increases in dead-space ventilation (6, 7). Moreover, increased V̇A/Q̇ heterogeneity with sustained heavy exercise does not result in a change in MRI-derived lung density measures 20 min following exercise (1). The multiple inert-gas elimination technique for determining V̇A/Q̇ has never been directly validated (3) which makes definitive statements about the development of exercise-induced edema difficult. Furthermore, regional estimates of where the edema (i.e., peribronchial and perivascular “cuffing”) occurs based on V̇A/Q̇ heterogeneity measures in humans are speculative. It appears that the indirect methods offer only cause for speculation on the presence of pulmonary edema while direct measurements via CT or MRI consistently fail to demonstrate changes in lung density.Accumulation of scattered anecdotal reports and circumstantial evidence is not proof of interstitial edema. In our view, the hypothesis continues to await experimental support.REFERENCES1. Burnham KJ , Arai TJ , Dubowitz DJ , Henderson AC , Holverda S , Buxton RB , Prisk GK , Hopkins SR. Pulmonary perfusion heterogeneity is increased by sustained, heavy exercise in humans. J Appl Physiol 107: 1559–1568, 2009.Link | ISI | Google Scholar2. Hopkins SR. Counterpoint: Pulmonary edema does occur in human athletes performing heavy sea-level exercise. J Appl Physiol; doi:10.1152/japplphysiol.01353-2009.Google Scholar3. Hopkins SR , Levin DL , Emami K , Kadlecek S , Yu J , Ishii M , Rizi RR. Advances in magnetic resonance imaging of lung physiology. J Appl Physiol 102: 1244–1254, 2007.Link | ISI | Google Scholar4. Prisk GK , Olfert IM , Arai TJ , Wagner PD , Hopkins SR. Rapid intravenous infusion of 20 ml/kg saline does not impair resting pulmonary gas exchange in the healthy human lung. J Appl Physiol 108: 53–59, 2010.Link | ISI | Google Scholar5. Schaffartzik W , Poole DC , Derion T , Tsukimoto K , Hogan MC , Arcos JP , Bebout DE , Wagner PD. VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema. J Appl Physiol 72: 1657–1667, 1992.Link | ISI | Google Scholar6. Tsukimoto K , Arcos JP , Schaffartzik W , Wagner PD , West JB. Effect of common dead space on VA/Q distribution in the dog. J Appl Physiol 68: 2488–2493, 1990.Link | ISI | Google Scholar7. Wagner PD , Gale GE , Moon RE , Torre-Bueno JR , Stolp BW , Saltzman HA. Pulmonary gas exchange in humans exercising at sea level and simulated altitude. J Appl Physiol 61: 260–270, 1986.Link | ISI | Google Scholar8. Wilmshurst PT. Pulmonary oedema induced by emotional stress, by sexual intercourse, and by exertion in a cold environment in people without evidence of heart disease. Heart (Br Cardiac Soc) 90: 806–807, 2004.Crossref | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation More from this issue > Volume 109Issue 4October 2010Pages 1274-1275 Copyright & PermissionsCopyright © 2010 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.01353.2009cPubMed20940440History Published online 1 October 2010 Published in print 1 October 2010 Metrics

Ultrasonic evidence of acute interstitial lung edema after SCUBA diving is resolved within 2–3h

Recently, an increase in extravascular lung water (EVLW) accumulation with diminished left ventricular contractility within 60 min after SCUBA diving was reported. We have observed previously that diving was associated with reduced diffusing lung capacity for carbon monoxide (DLCO) and arterial oxygen pressure for up to 60-80 min postdive. Here we investigated whether increased EVLW persists 2-3h after successive deep dives in a group of seven male divers. The echocardiographic indices of pulmonary water accumulation (ultrasound lung comets (ULC)) and left ventricular function, respiratory functional measurements and arterial oxygen saturation (SaO(2)) were assessed 2-3h post diving, while venous gas bubbles (VGB) and the blood levels of NT-proBNP and proANP were analyzed 40 min after surfacing. Spirometry values, flow-volume, DLCO, SaO(2) and ULC were unchanged after each dive, except for significant increase in ULC after the second dive. Left ventricular function was reduced, while NT-proBNP and proANP levels were significantly elevated after majority of dives, suggesting a cardiac strain.

Redistribution of Pulmonary Blood Flow Impacts Thermodilution-based Extravascular Lung Water Measurements in a Model of Acute Lung Injury

Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. The authors hypothesized that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Anesthetized, mechanically ventilated canines were instrumented with PiCCO (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computed tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly after endotoxin administration. Computed tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computed tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW.

Maternal haemodynamics and lung water content during percutaneous fetoscopic interventions under general anaesthesia

The purpose of our study was to evaluate the maternal cardiopulmonary function and lung water content during percutaneous fetoscopic interventions under general maternal-fetal anaesthesia and continuous tocolytic medication. We prospectively studied 13 women between 19 and 30 weeks of gestation undergoing percutaneous fetoscopic procedures that were performed under general maternal-fetal anaesthesia and tocolysis using indomethacin. Invasive haemodynamic monitoring using pulmonary artery catheters and the transpulmonary indicator dilution technique was applied to determine intrathoracic blood volume (ITBV), cardiac output, and extravascular lung water (EVLW). Pulmonary vascular permeability was estimated as the ratio of EVLW/ITBV. Measurements were performed during and for 24 h after the interventions. Respective mean (SD) maternal ITBV and cardiac output were 894 (191) ml min(-1) m(-2) and 3.29 (0.51) litre(-1) min(-1) m(-2) intraoperatively, and 843 (169) ml min(-1) m(-2) and 4.47 (0.55) litre min(-1) m(-2) during the first postoperative day. EVLW was 7.9 (2.7) ml kg(-1) during the interventions and 7.7 (1.8) ml kg(-1) during the first postoperative day. The pulmonary vascular permeability index was calculated as 0.35 (0.06) during the interventions and 0.38 (0.14) for the first postoperative day. Clinically overt pulmonary oedema was not detected in any woman while pulmonary gas exchange remained normal. In mid-gestational women undergoing percutaneous fetoscopic interventions under general maternal-fetal anaesthesia, cardiopulmonary function remained stable. However, a moderate increase in EVLW and pulmonary vascular permeability indicates an increased risk for maternal pulmonary oedema.

What happens after pneumonectomy? A prospective study using the transpulmonary thermodilution method

event is the augmentation of the extravascular lung water (EVLW) that transudates into the alveolar space, impairing ventilation. In the experimental model, thoracotomy, rapid fluid infusion, and manipulation of the lung result in an increase in EVLW. 3 In humans, the transpulmonary thermodilution method is a reliable technique for EVLW assessment, even if a moderate overestimation as compared with the double-indicator method is expected in case of pneumonectomy. 4 Given the paucity of available information, this studywas designed tomonitor EVLW modifications occurring early after pneumonectomy in humans.

Prognostic Value of Extravascular Lung Water Assessed With Ultrasound Lung Comets by Chest Sonography in Patients With Dyspnea and/or Chest Pain

Background Ultrasound lung comets (ULCs) consist of multiple comet tails originating from water-thickened interlobular septa. They are a new echographic tool to assess the pathologic increase in extravascular lung water, which is a possible harbinger of impending acute heart failure. The objective was to assess the prognostic value of ULCs in patients with dyspnea and/or chest pain syndrome at hospital admission. Methods and Results A total of 290 consecutive in-hospital patients (aged 68 ± 13 years) admitted for dyspnea and/or chest pain syndrome were evaluated on admission with a comprehensive two-dimensional and Doppler echocardiographic evaluation and chest sonography with ULC assessment. A patient ULC score was obtained by summing the number of comets from each of the scanning spaces in the anterior right and left hemithoraxes, from the second to fifth intercostal spaces. All patients were followed up for a median period of 16 months (interquartile range: 2.8–29.1 months). During the follow-up, 62 events occurred: 19 cardiac deaths, 3 nonfatal myocardial infarctions, 20 acute heart failures requiring hospitalization, and 20 noncardiac deaths. The 16-month event-free survival was highest in patients with no ULCs and lowest in patients with severe (>30) ULCs at entry (70% vs 19%, P = .0007). At univariate analysis, ULCs (hazard ratio [HR] 2.349; confidence interval [CI] 1.364–4.044) were more powerful predictors than other echocardiographic variables of recognized prognostic value, including ejection fraction (HR 0.974; 95% CI 0.958–0.99) and wall motion score index (HR 1.628; CI 1.15–2.304). On multivariable analysis, ULCs provided additional prognostic information (HR 1.9; 95% CI 1.1–3.4) on diabetes (HR 2.05; 95% CI 1.2–3.5) and New York Heart Association class (HR 1.3; 95% CI 1.0–1.6). Conclusion ULCs are a simple user-friendly, radiation-free bedside sign of extravascular lung water. They provide useful information for the prognostic stratification of patients with dyspnea and/or chest pain syndrome.

Role of platelet activating factor in pathogenesis of acute respiratory distress syndrome

Role of platelet activating factor in pathogenesis of acute respiratory distress syndrome

Impact of low and high tidal volumes on the rat alveolar epithelial type II cell proteome.

Mechanical ventilation with high tidal volumes leads to increased permeability, generation of inflammatory mediators, and damage to alveolar epithelial cells (ATII). To identify changes in the ATII proteome after two different ventilation strategies in rats. Rats (n = 6) were ventilated for 5 hours with high- and low tidal volumes (VTs) (high VT: 20 ml/kg; low VT: 6 ml/kg). Pooled nonventilated rats served as control animals. ATII cells were isolated and lysed, and proteins were tryptically cleaved into peptides. Cellular protein content was evaluated by peptide labeling of the ventilated groups with (18)O. Samples were fractionated by cation exchange chromatography and identified using electrospray tandem mass spectrometry. Proteins identified by 15 or more peptides were statistically compared using t tests corrected for the false discovery rate. High Vt resulted in a significant increase in airspace neutrophils without an increase in extravascular lung water. Compared with low-VT samples, high-VT samples showed a 32% decrease in the inositol 1,4,5-trisphosphate 3 receptor (p < 0.01), a 34% decrease in Na(+), K(+)-ATPase (p < 0.01), and a significantly decreased content in ATP synthase chains. Even low-VT samples displayed significant changes, including a 66% decrease in heat shock protein 90-beta (p < 0.01) and a 67% increase in mitochondrial pyruvate carboxylase (p < 0.01). Significant differences were found in membrane, acute phase, structural, and mitochondrial proteins. After short-term exposure to high-VT ventilation, significant reductions in membrane receptors, ion channel proteins, enzymes of the mitochondrial energy system, and structural proteins in ATII cells were present. The data supports the two-hit concept that an unfavorable ventilatory strategy may make the lung more vulnerable to an additional insult.

Physiopathologie de l'œdème pulmonaire

Pulmonary edema is defined by an abnormal increase in extravascular lung water. There is a physiologic liquid flux from the capillary to the interstitium, which is evacuated by the lymphatic vessels. Edema results from the imbalance between the increase in transudation or exsudation and the mechanisms of protection such as the lymphatic drainage or the resorption of alveolar liquid through the epithelium. Alveolar flooding occurs if interstitial space is saturated or in case of failure of the blood-gas barrier due to a major increase in microvascular pressure or due to an alveolar distension. The absorption of alveolar liquid is an active process following an osmotic gradient through the epithelium.

Intense hypoxic cycle exercise does not alter lung density in competitive male cyclists

We tested the hypothesis that intense short duration hypoxic exercise would result in an increase in extravascular lung water (EVLW), as evidenced by an increase in lung density. Using computed tomography (CT), baseline lung density was obtained in eight highly trained male cyclists (mean +/- SD: age = 28 +/- 8 years; height = 180 +/- 9 cm; mass = 71.6 +/- 8.2 kg; VO2max= 65.0 +/- 5.2 ml kg min(-1)). Subjects then completed an intense hypoxic exercise challenge on a cycle ergometer and metabolic data, HR and %S(p)O2 were recorded throughout. While breathing 15% O2, subjects performed five 3 km cycling intervals (mean power, 286 +/- 20 W; HR = 91 +/- 4% HRmax) separated by 5 min of recovery. From a resting hypoxic S(p)O2 of 92 +/- 4%, subjects further desaturated during exercise to 76 +/- 3%. CT scans were repeated 76 +/- 10 min (range 63-88 min) following the completion of exercise. There was no change in lung density from pre (0.18 +/- 0.02 g ml(-1)) to post-exercise (0.18 +/- 0.04 g ml(-1)). The substantial reduction in S(p)O2 may be explained by a number of potential mechanisms, including decreased pulmonary diffusion capacity, alveolar hypoventilation, reduced red cell transit time, ventilation/perfusion inequality or a temperature and pH induced rightward-shift in the oxyhaemoglobin dissociation curve. Alternatively, the integrity of the blood gas barrier may have been disrupted without any measurable increase in lung density.

Positive End-expiratory Pressure Ventilation Increases Extravascular Lung Water Due to a Decrease in Lung Lymph Flow

Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the lung lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.

Evolving Practices in Critical Care and Potential Implications for Management of Acute Kidney Injury

Acute kidney injury (AKI) is a common complication in hospitalized patients, with an incidence of 3 to 10% (1–4). In-hospital mortality rates that are associated with AKI remain high, in the range of 30 to 70% (5–8), despite significant improvements in dialytic technology as well as important advances in critical care, which have resulted in improved survival for other critical illnesses, including acute lung injury and sepsis (9). These improvements include continuous renal replacement therapies, which allow for continuous removal of solutes and fluid and may be tolerated better from a hemodynamic standpoint, and biocompatible dialysis membranes, which are associated with reduced complement and granulocyte activation. In general, indications for dialysis in the acute care setting have been extrapolated from those that are applied in chronic kidney disease, including volume overload that is refractory to diuretic therapy; electrolyte abnormalities (in particular hyperkalemia); uremic complications (pericarditis or pleuritis); severe acidosis (pH < 7.20); and selected toxic ingestions, such as methanol, ethylene glycol, and other water-soluble agents (10,11). However, the evidence base supporting specific dialysis practices in the acute care setting is limited. For example, several studies that were completed in the 1960s and 1970s compared “early” and “late” initiation of dialysis, using blood urea nitrogen (BUN) to define early and late (Table 1). These studies primarily were cohort studies that used historical controls, not randomized, clinical trials. The results of these investigations, along with extrapolation from the ESRD population, promoted recent practice patterns. Currently, many nephrologists often delay dialysis in the acute care setting until the patient has an impending complication of AKI, such as hyperkalemia leading to cardiac arrhythmias, acidosis resulting in hypotension, or oliguria leading to volume overload or hypoxemia, or until the BUN exceeds 100 mg/dl (18). Given differences in protein catabolism, …

Do the data obtained by the PiCCO system enable one to differentiate between direct ALI/ARDS and indirect ALI/ARDS?

It is known that measurement of the intrathoracic blood volume (ITBV) is a more accurate estimate of cardiac preload than pressure measurements using central venous or pulmonary artery occlusion pressures. Extravascular lung water (EVLW) is defined as the value of the intrathoracic thermal volume minus the ITBV. An increase in EVLW is the pathophysiological basis for the development of pulmonary edema (PE). There is evidence to suggest that therapy to reduce EVLW may improve outcome in the critically ill patient. The bedside assessment of EVLW may be very useful in identifying and quantifying PE, and hence in selecting patients who might benefit from a fluid restriction/depletion therapeutic strategy based on EVLW monitoring. The PiCCO (Pulsion, Munich, Germany) provides an estimate of the ITBV, EVLW, and permeability index (PI) via a single transpulmonary thermodilution technique. PE is defined as the abnormal accumulation of fluid in the extravascular space of the lung. ALI/ARDS is characterized by pulmonary edema. PE consists of increased hydrostatic PE (cardiogenic PE) and increased permeability PE (ALI/ARDS). Increased permeability PE (ALI/ARDS) is further classified into direct lung injury type and indirect lung injury type. PI was calculated as the ratio of EVLW to ITBV, which was previously shown to reflect permeability of the alveolar-capillary barrier. The early recognition and differential diagnosis of direct lung injury and indirect lung injury may be challenging.

Pulmonary Oedema following Exercise in Humans

Pulmonary physiologists have documented many transient changes in the lung and the respiratory system during and following exercise, including the incomplete oxygen saturation of arterial blood in some subjects, possibly due to transient pulmonary oedema. The large increase in pulmonary arterial pressure during exercise, leading to either increased pulmonary capillary leakage and/or pulmonary capillary stress failure, is likely to be responsible for any increase in extravascular lung water during exercise. The purpose of this article is to summarise the studies to date that have specifically examined lung water following exercise. A limited number of studies have been completed with the specific purpose of identifying pulmonary oedema following exercise or a similar intervention. Of these, approximately 50% have observed a positive change and the remaining have provided results that are either inconclusive or show no change in extravascular lung water. While it is difficult to draw a firm conclusion from these studies, we believe that pulmonary oedema does occur in some humans following exercise. As such, this is a phenomenon of significance to pulmonary and exercise physiologists. This possibility warrants further study in the area with more precise measurement tools than has previously been undertaken.

Small Increases in Extravascular Lung Water Are Accurately Detected by Transpulmonary Thermodilution

Detection of small (10-20%) increases in lung water may be relevant to detect incipient pulmonary edema but no clinically usable method has demonstrated this capability to date. In six pigs weighing 28 to 35 kg, we performed 18 determinations of extravascular lung water (EVLW; transpulmonary thermodilution method) before and immediately after the intratracheal introduction of 50 mL of saline solution. Six determinations were performed in normal lung and 12 in edematous lung. In normal lung, the mean of EVLW increased from 245 +/- 18 mL to 288 +/- 19 mL (p < 0.001) after the intratracheal introduction of 50 mL of saline solution; therefore, 43 of the 50 mL (84%) were detected (range, 37-48 mL). In edematous lung, the EVLW increased from 491 +/- 106 mL to 530 +/- 108 mL after the introduction of 50 mL of saline solution; therefore, 39 of the 50 mL (77%) were detected (range, 15-67 mL). The transpulmonary thermodilution technique accurately detects small increases in extravascular lung water and may permit accurate diagnosis of incipient pulmonary edema.

Protective effect of endogenous β-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice

Some investigators have reported that endogenous beta-adrenoceptor tone can provide protection against acute lung injury. Therefore, we tested the effects of beta-adrenoceptor inhibition in mice with acute Escherichia coli pneumonia. Mice were pretreated with propranolol or saline and then intratracheally instilled with live E. coli (10(7) colony-forming units). Hemodynamics, arterial blood gases, plasma catecholamines, extravascular lung water, lung permeability to protein, bacterial counts, and alveolar fluid clearance were measured. Acute E. coli pneumonia was established after 4 h with histological evidence of acute pulmonary inflammation, arterial hypoxemia, a threefold increase in lung vascular permeability, and a 30% increase in extravascular lung water as an increase in plasma catecholamine levels. beta-Adrenoceptor inhibition resulted in a marked increase in extravascular lung water that was explained by both an increase in lung vascular permeability and a reduction in net alveolar fluid clearance. The increase in extravascular lung water with propranolol pretreatment was not explained by an increase in systemic or vascular pressures. The increase in lung vascular permeability was explained in part by anti-inflammatory effects of beta-adrenoceptor stimulation because plasma macrophage inflammatory protein-2 levels were higher in the propranolol pretreatment group compared with controls. The decrease in alveolar fluid clearance with propranolol was explained by a decrease in catecholamine-stimulated fluid clearance. Together, these results indicate that endogenous beta-adrenoceptor tone has a protective effect in limiting accumulation of extravascular lung water in acute severe E. coli pneumonia in mice by two mechanisms: 1) reducing lung vascular injury and 2) upregulating the resolution of alveolar edema.

Effect of pulmonary artery pressure on extravascular lung water in an experimental model of acute lung injury

Lung edema can be influenced by hemodynamic changes in pulmonary circulation. The aim of this study was to evaluate, in an experimental model of acute lung injury, the effect on extravascular lung water (EVLW) of an increase in pulmonary artery pressure (Ppa) without changes in cardiac output and wedge pressure. Lung edema was produced by an intravenous oleic acid infusion in mixed-breed pigs weighing 25-31 kg, which, after 20 min, were randomly assigned to a control group (100% FiO(2)) (n = 6) or a high Ppa group (21% FiO(2)) (n = 7). An increase in pulmonary artery pressure of at least 40% over baseline was produced in the high Ppa group by alveolar hypoxia. Hemodynamic, ventilatory and gas exchange parameters were collected at regular intervals. Pulmonary, wedge and capillary pressures were measured with a pulmonary artery catheter and the occlusion technique. EVLW was calculated gravimetrically. At 240 min, both gravimetric-measured EVLW and mean pulmonary artery pressures were significantly higher (P < 0.05) in high Ppa animals vs. controls (12.06 +/- 4.21 vs. 7.98 +/- 2.46 ml/kg and 39.0 +/- 1.3 vs. 26.6 +/- 4.7 mmHg, respectively). Cardiac output (6.8 +/- 2.5 vs. 7.3 +/- 1.3) and pulmonary wedge pressures (9.2 +/- 1.7 vs. 9.4 +/- 2.8 mmHg) were similar. A difference was detected in pulmonary capillary pressures [17.0 +/- 3.3 (high Ppa) vs. 13.8 +/- 2.7 mmHg (controls)] but did not reach statistical significance. In this model, an increase in pulmonary artery pressure by alveolar hypoxia produces an increase in extravascular lung water, probably related to changes in pulmonary capillary pressures.