Increase In Extravascular Lung Water Research Articles

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.

Inhibition of Acid-induced Lung Injury by Hyperosmolar Sucrose in Rats

Acid aspiration causes acute lung injury (ALI). Recently, we showed that a brief intravascular infusion of hyperosmolar sucrose, given concurrently with airway acid instillation, effectively blocks the ensuing ALI. The objective of the present study was to determine the extent to which intravascular infusion of hyperosmolar sucrose might protect against acid-induced ALI when given either before or after acid instillation. Our studies were conducted in anesthetized rats and in isolated, blood-perfused rat lungs. We instilled HCl through the airway, and we quantified lung injury in terms of the extravascular lung water (EVLW) content, filtration coefficient (Kfc), and cell counts and protein concentration in the bronchoalveolar lavage. We infused hyperosmolar sucrose via the femoral vein. In anesthetized rats, airway HCl instillation induced ALI as indicated by a 52% increase of EVLW and a threefold increase in Kfc. However, a 15-min intravenous infusion of hyperosmolar sucrose given up to 1 h before or 30 min after acid instillation markedly blunted the increases in EVLW, as well as the increases in cell count, and in protein concentration in the bronchoalveolar lavage. Hyperosmolar pretreatment also blocked the acid-induced increase of Kfc. Studies in isolated perfused lungs indicated that the protective effect of hyperosmolar sucrose was leukocyte independent. We conclude that a brief period of vascular hyperosmolarity protects against acid-induced ALI when the infusion is administered shortly before, or shortly after, acid instillation in the airway. The potential applicability of hyperosmolar sucrose in therapy for ALI requires consideration.

Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange.

Sepsis-induced acute lung injury is still associated with high morbidity and mortality. The pathophysiology is complex, and markers of injury include increased extravascular lung water. To evaluate the effects of the novel dual endothelin receptor antagonist tezosentan on endotoxin-induced changes in extravascular lung water and gas exchange, 16 pigs were anaesthetized and catheterized. Twelve animals were subjected to 5 h of endotoxemia. After 2 h, six of these animals received a bolus of tezosentan 1 mg kg(-1) followed by a continuous infusion of 1 mg kg(-1) h(-1) to the end of the experiment at 5 h. Conventional pulmonary and hemodynamic parameters were measured. Extravascular lung water was determined in these pigs after 5 h of endotoxemia, as well as in the four additional nonendotoxemic sham animals. Tezosentan in the current dosage counteracted the deterioration of lung function caused by endotoxin, as measured by dead space, venous admixture, and compliance. In addition, pulmonary hypertension was attenuated. Tezosentan had a marked effect on the endotoxin-induced increase in extravascular lung water that was reduced to levels observed in nonendotoxemic sham animals. These results suggest that endothelin is involved in endotoxin-induced lung injury and the development of pulmonary edema. Dual endothelin receptor antagonism may be of value in the treatment of sepsis-related acute lung injury.

Síndrome cardiopulmonar por Hantavirus: utilidad de la monitorización con el sistema PiCCO

We report a 68 years old man, farmer from the metropolitan region, admitted with a Hantavirus Cardiopulmonary Syndrome. The diagnosis was made using serologic test and was later confirmed by the Public Health Institute. He evolved to an early multiple organ failure, requiring high concentrations of oxygen and invasive ventilatory assistance, vasopressor drugs and renal replacement therapy. Swan Ganz and PiCCO were used simultaneously for hemodynamic monitoring. Treatment consisted in global support therapy, antimicrobial therapy and systemic corticosteroids. Intrathoracic blood volume was a more reliable parameter than pulmonary capillary wedge pressure for the assessment of preload. As expected in situations of increased vascular permeability, there was an increase in extravascular lung water. There was a good correlation between extravascular lung water and oxygenation parameters (PaO2/FiO2 and oxygenation index). PiCCO system may become a helpful tool in the management of patients with Hantavirus Cardiopulmonary Syndrome.

Intrathoracic blood volume in a patient with pulmonary embolism

Intrathoracic blood volume in a patient with pulmonary embolism

Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude

Recent work suggests that treatment with inhaled beta(2)-agonists reduces the incidence of high-altitude pulmonary edema in susceptible subjects by increasing respiratory epithelial sodium transport. We estimated respiratory epithelial ion transport by transepithelial nasal potential difference (NPD) measurements in 20 normal male subjects before, during, and after a stay at 3,800 m. NPD hyperpolarized on ascent to 3,800 m (P < 0.05), but the change in potential difference with superperfusion of amiloride or isoprenaline was unaffected. Vital capacity (VC) fell on ascent to 3,800 m (P < 0.05), as did the normalized change in electrical impedance (NCI) measured over the right lung parenchyma (P < 0.05) suggestive of an increase in extravascular lung water. Echo-Doppler-estimated pulmonary artery pressure increases were insufficient to cause clinical pulmonary edema. There was a positive correlation between VC and NCI (R(2) = 0.633) and between NPD and both VC and NCI (R(2) = 0.267 and 0.418). These changes suggest that altered respiratory epithelial ion transport might play a role in the development of subclinical pulmonary edema at high altitude in normal subjects.

Extracorporeal membrane oxygenation (ECMO) in adults

Zusammenfassung Trotz anhaltender Diskussion ist die extrakorporale Membranoxygenierung (extracorporeal membrane oxygenation, ECMO) auch bei erwachsenen Patienten zu einem festen Bestandteil der therapeutischen Optionen in der Behandlung des akuten Lungenversagens (ARDS, acute respiratory distress syndrome) geworden. Die beiden bislang durchgeführten randomisierten Vergleichsstudien konnten allerdings keinen Vorteil im Hinblick auf die Letalität verglichen mit konventioneller Beatmungstherapie belegen. In der Konsequenz resultierte aus beiden Studien keine Empfehlung für die ECMO-Therapie (1–3). Mittlerweile liegen weitreichende weltweite Erfahrungen (Gesamtzahl der therapierten erwachsenen Patienten Ende 2001 ca. 1000) vor. Wachsende Erfahrung und verbesserte Technik haben die Rate technischer Komplikationen der extrakorporalen Lungenersatztherapie deutlich reduziert. Aus einer Reihe von Gründen ist in der jüngsten Zeit die Inzidenz des Einsatzes von ECMO dennoch deutlich rückläufig. Einzelne Ein- und Ausschlusskriterien variieren zwischen den verschiedenen ECMO-Zentren. Potentielle Reversibilität der aktuellen Lungenschädigung und bei ausgeschöpfter konventioneller Therapie Fortbestand einer lebensbedrohlichen Gasaustauschstörung stellen jedoch übereinstimmende Grundvoraussetzung für die Durchführung einer ECMO-Therapie dar. Gebräuchliche Kriterien sind ein Murray lung injury score >3,5 (Röntgen-Befund, PaO2/FiO2 Ratio, statische Compliance=Cstat, PEEP) eine Morel-Klassifikation >3 (Röntgen-Befund, AaDO2/FiO2-Index, Cstat, PEEP), eine AaDO2 >600mmHg, ein intrapulmonaler Shunt QS/QT >30% und eine Erhöhung des extravaskulären Lungenwassers auf >15ml/kg KG. In manchen Zentren stellt darüber hinaus die Dauer der maschinellen Beatmung (<12 Tage) ein weiteres Kriterium dar. Nach unserer Erfahrung hat sich in der Praxis nach Optimierung des Beatmungsmanagements und nach Ausschöpfung aller supportiven Maßnahmen inklusive der Bauchlage ein Vorgehen bewährt, das sich an der Höhe der PaO2/FiO2 Ratio orientiert, dabei gelten als Verlegungskriterium in ein ECMO-Zentrum <100 mmHg, als Sofortkriterium für die ECMO-Therapie <50 mmHg. Das Vorgehen im Intermediärbereich ist vom klinischen Verlauf bestimmt (4). Weitgehend akzeptierte absolute Kontraindikationen (KI) sind: (1) prognostisch ungünstige (terminale) konsumierende Erkrankungen, (2) ZNS-Schädigung mit ungünstiger Prognose (3) fortgeschrittene chronische Lungenerkrankung sowie (4) weit fortgeschrittenes Multiorganversagen. Relative KI sind manifeste Immunsuppression, aktive Blutungen (>2 Erythrozytenkonzentrate pro h), Alter >60 Jahre und – besonders in den USA – die Dauer der vorausgehenden invasiven Beatmung. Nach unserer Erfahrung optimiert ein frühzeitiger Kontakt zu einem ECMO-Referenzzentrum die Identifikation von Patienten die von einer ECMO-Therapie profitieren, die Gesamttherapie, den Transport und das Outcome. Auf Grund der hohen apparativen und personellen Anforderungen bei gleichzeitig sinkender Inzidenz sollte ECMO im Erwachsenensektor auf eine kleine Zahl Referenzzentren mit großer Erfahrung begrenzt bleiben. Damit lässt sich gleichzeitig eine ausreichende Routine aufrechterhalten. In Zeiten sich wandelnder ökonomischer Rahmenbedingungen kommt einer kritischen Indikationsstellung und hochqualifizierten Durchführung der ECMO-Therapie eine besondere Bedeutung zu.

The Thoracic Surgical Patient: Initial Postoperative Care

Thoracic surgery patients require complex perioperative care. Accurate preoperative screening of pulmonary conditions can only partially predict the requirement of postoperative mechanical ventilation. In general, extensive lung resections are associated with significant gas exchange abnormalities. In this group of patients, a mechanical ventilation strategy protective from barotrauma and volutrauma and a conservative use of intraoperative and postoperative fluid limit the inevitable increase of extravascular lung water and gas exchange impairment. A wise use of pulmonary vasodilatatory and bronchodilating drugs and airway manipulation including suctioning and bronchoscopy can also significantly affect postoperative respiratory dysfunction and hospital stay. A number of acute postoperative complications have been described specifically related to the type of surgery or pleural space suctioning devices. The role of the intensivist is to maintain a low index of suspicion for such complications, when acute hemodynamic or pulmonary deterioration occurs and be prepared to immediately correct them or alert the thoracic surgeon. In general, when these roles are observed, thoracic surgery can be safely performed with a low perioperative mortality.

Oleic acid-induced lung injury: thin-section CT evaluation in dogs.

To validate lung attenuation measurements for quantifying extravascular lung water in oleic acid-induced pulmonary edema, compare subjective assessment with attenuation measurements, and compare this permeability-type pulmonary edema with hydrostatic-type pulmonary edema. Thin-section computed tomography (CT) and pulmonary hemodynamic examinations were performed sequentially in six dogs before and after intravenous administration of 0.08 mg of oleic acid per kilogram of body weight. Extravascular lung water and pulmonary capillary pressure were measured. Results were compared with those reported in a canine model of hydrostatic edema. Oleic acid induced a progressive increase in extravascular lung water without a change in capillary pressure, which indicated pure permeability-type edema. Ground-glass opacification was detected as soon as extravascular lung water increased. Lung attenuation was highly correlated to extravascular lung water (r = 0.76, P<.001), as in hydrostatic edema, but was characterized by an almost absent gravitational gradient. Thin-section CT is sensitive for early detection and quantification of oleic acid-induced pulmonary edema in a canine model. Different from early canine hydrostatic edema, which is characterized by a gravitational gradient, early oleic acid-induced pulmonary edema in a supine dog is characterized by nearly homogeneous distribution, except for ventral sparing.

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 (PaO 2: 87 ± 11 mmHg versus control group 128 ± 11) and an increased permeability of the alveolarcapillary 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.

Hydrostatic pulmonary edema: evaluation with thin-section CT in dogs.

To identify the hemodynamic determinants of ground-glass opacification on thin-section computed tomographic (CT) scans of hydrostatic pulmonary edema and to compare attenuation and subjective assessments of ground-glass opacification with extravascular lung water. Left atrial pressure, pulmonary arterial pressure, effective pulmonary capillary pressure, and extravascular lung water were measured in six dogs before and during progressive increase of effective pulmonary capillary pressure. A thin-section CT scan was obtained at each step. Lung attenuation and subjective assessments of ground-glass opacification were compared with hemodynamic variables and extravascular lung water. Ground-glass opacification was identified when effective pulmonary capillary pressure equaled critical pulmonary capillary pressure. Extravascular lung water increased, and the distribution curve of lung attenuation coefficients shifted to higher attenuation from the second measurement at an effective pulmonary capillary pressure greater than the critical pulmonary capillary pressure. Attenuation was highly correlated (r = 0.98, P < .001) with extravascular lung water; ground-glass opacification was detected before a significant (P = .615, analysis of variance) increase in extravascular lung water. Thin-section CT depicts ground-glass opacification when effective pulmonary capillary pressure equals critical pulmonary capillary pressure and before a detectable increase in extravascular lung water. Attenuation reflects extravascular lung water.

Role of Platelet-Activating Factor on Extravascular Lung Water after Coronary Reperfusion in Dogs.

Platelet-activating factor (PAF), one of the harmful substances released after coronary reperfusion, has been reported to increase pulmonary vascular permeability and induce pulmonary edema. In this study, we sought to examine the possible role of PAF in the genesis of pulmonary edema after coronary reperfusion. Extravascular lung water (EVLW) was measured by the thermal-dye double indicator dilution method during coronary ligation and after reperfusion in situ in dogs. The proximal left anterior descending coronary artery was occluded for 15 min and reperfused in 5 dogs (group 1), while five other dogs (group 2) were treated with PAF-antagonist (TCV-309, 1 mg/kg) before coronary artery occlusion. EVLW and hemodynamic indices were measured at baseline, 15 min of coronary occlusion, and 15 and 30 min after coronary reperfusion. EVLW increased at 15 min of coronary occlusion in both groups, but there was no significant difference between the two groups (6.4 to 10.3 ml/kg and 5.4 to 7.1 ml/kg in groups 1 and 2, respectively). After coronary reperfusion, EVLW increased further in group 1 (6.4 to 16.5 ml/kg, p < 0.01), but no further increase was observed in group 2 at 30 min after coronary reperfusion. There were no significant differences in hemodynamic indices between the two groups throughout the test. Thus, PAF-antagonist attenuated the increase in EVLW after coronary reperfusion independent of hemodynamic indices, and hence, PAF may play an important role in the genesis of pulmonary edema caused by coronary reperfusion.

Epileptic Sudden Death: Animal Models

The pathologic hallmark of sudden unexpected death in epilepsy (SUDEP) in humans is pulmonary edema. In an animal model of seizures, pulmonary vascular pressure, but not systemic pressure, increases in proportion to seizure duration. The induced pulmonary vascular hypertension drives fluid out of the vascular compartment into the lung parenchyma. Blocking intra-ictal pulmonary vascular pressure elevations prevents changes in the observed doubling of the pulmonary transcapillary fluid flux. In this animal model, the main difference between surviving animals and those that die during the seizure is apnea, with a precipitous fall in the partial pressure of oxygen (pO(2)) and a parallel elevation in the partial pressure of carbon dioxide (pCO(2)) recorded in nonsurvivors. Pulmonary artery and left atrial pressures in animals that die are double those of surviving animals, with a resultant increase in extra-vascular lung water at postmortem examination. The pulmonary edema is due to the combined effects of seizure- and hypoxia-induced pulmonary vascular hypertension. This animal model reproduces both death during epilepsy and pulmonary edema at postmortem examination. The etiology of the pulmonary edema appears to be that of pulmonary vascular hypertension, and the etiology of sudden death appears to be that of centrally induced apnea.

Inhibition of CD18 or CD11b attenuates acute lung injury after acid instillation in rabbits.

Acid-induced lung injury is mediated primarily by activated neutrophils. Although a prior study demonstrated that acid-induced neutrophil influx into the air spaces was not CD18 dependent, we hypothesized that either a neutralizing anti-CD18 monoclonal antibody (MHM23) or a neutrophil inhibitory factor (NIF), NIF (CD11b,18), might attenuate acid-induced lung injury in rabbits by interfering with neutrophil activation. This hypothesis derived from in vitro stu ies that reported that anti-CD18 therapy prevented tumor necrosis factor-alpha-induced neutrophil activation. Hydrochloric acid (pH = 1.5 in one-third normal saline) or one-third normal saline (4 ml/kg) was instilled into the lungs of ventilated, anesthetized rabbits. The rabbits were studied for 6 h. In acid-instilled rabbits without the anti-CD18 monoclonal antibody or NIF (CD11b,18), severe lung injury developed. In acid-instilled rabbits, pretreatment (5 min before acid) with the anti-CD18 monoclonal antibody (2 mg/kg i.v.) or pretreatment with the NIF (anti-CD11b,18, 10 mg/kg i.v.) prevented 50-70% of acid-induced abnormalities in oxygenation, the increase in extravascular lung water, and extravascular protein accumulation. The anti-CD18 monoclonal antibody was associated with a significant increase in air space neutrophils by bronchoalveolar lavage, suggesting that the neutrophils respond normally to chemotactic stimuli but that the neutrophils did not injure the lung even though they accumulated in the air spaces. In summary, neutralization of CD18 attenuates the acute lung injury after acid instillation without reducing the number of neutrophils in the air spaces, suggesting that anti-CD18 therapy may be beneficial because of its capacity to reduce neutrophil activation.

Alveolar Epithelial Fluid Clearance Mechanisms Are Intact After Moderate Hyperoxic Lung Injury In Rats

The capacity of the alveolar epithelial barrier to remove excess alveolar fluid from the airspaces of the lung was studied in an experimental model of moderate hyperoxic lung injury. Rats were exposed to 100% oxygen for 40 h in an exposure chamber and compared with control animals exposed to room air. Extravascular lung water was calculated gravimetrically. Alveolar and lung liquid clearance were studied over 1 h by instillation of a 5% albumin solution with 1.5 microCi of 125I-labeled albumin (6 mL/kg into both lungs). The concentration of both the unlabeled and labeled albumin was used to calculate alveolar liquid clearance. Hyperoxic rats developed pulmonary edema, with a 33% increase in extravascular lung water to 5.3 +/- 0.1 g of water per gram of dry lung, compared with 4.0 +/- 0.2 g of water per gram of dry lung in control rats (p < 0.05). This degree of edema was associated with a significant increase in the alveolar-arterial oxygen difference (241 +/- 61 vs 124 +/- 14 mm Hg in control animals exposed to room air, p < 0.05). Despite this moderate degree of lung injury, alveolar fluid clearance was normal (30 +/- 3%) compared with control rats (33 +/- 6%). Furthermore, the hyperoxic injured rats responded normally to an exogenous beta-adrenergic agonist (terbutaline, 10(-4) mol/L) with a 67% increase in the rate of alveolar liquid clearance (50 +/- 5%). Thus, in the setting of moderate hyperoxic lung injury, the alveolar epithelial barrier is still capable of removing fluid at a normal rate and responding to beta-adrenergic agonist treatment. These experimental results have potential clinical implications for patients with acute lung injury.

Ventilation with positive end-expiratory pressure reduces extravascular lung water and increases lymphatic flow in hydrostatic pulmonary edema.

To analyze the effect of different levels of positive end-expiratory pressure (PEEP) on extravascular lung water and on lymphatic drainage through the thoracic duct during hydrostatic pulmonary edema. Randomized, controlled, experimental study. Research laboratory of a tertiary care hospital. Eighteen beagle dogs weighing between 10 and 19 kg. Dogs were anesthetized and cannulated via a thoracic duct. Hydrostatic pulmonary edema was provoked by inflating the balloon of a Foley catheter in the left atrium. Different amounts of PEEP were applied. Extravascular lung water was determined by the double indicator dilution method (indocyanine green in glucoside solution at 0 degree C), and lymphatic drainage was measured every 30 mins. After a baseline measurement, the left atrial pressure was increased to 24 to 26 mm Hg, and measurements were recorded after 30, 60, 90, and 120 mins. The animals were divided into three groups. Group I (n = 6): PEEP of 20 cm H2O was instituted at 120 mins, and the other determinations were made without PEEP; group II (n = 7): PEEP of 10 cm H2O was instituted at 60 and 90 mins; group III (n = 5): PEEP of 20 cm H2O was instituted at 60 and 90 mins. Extravascular lung water increased after the increase of left atrial pressure in all three groups. After 90 mins, the extravascular lung water was significantly greater (p < .01) in group I (no PEEP application) at 21.2 +/- 5.1 mL/kg than in groups II and III (with 10 and 20 cm H2O of PEEP) at 12.8 +/- 2.01 and 14.8 +/- 4.8 mL/kg, respectively. Lymphatic drainage tended to increase over time in all three groups. Ninety minutes after the left atrial pressure increase, lymphatic drainage was significantly greater (p < .05) in group II, at 6.06 +/- 2.53 mL/kg/30 mins, than in group I, at 2.83 +/- 0.76 mL/kg/30 mins. a) The application of PEEP levels of between 10 and 20 cm H2O limits the increase of extravascular lung water in cases of hydrostatic pulmonary edema; and b) the application of 10 cm H2O of PEEP increases the lymphatic flow through the thoracic duct.

Inhibition of cytochrome P-450 attenuates hypoxemia of acute lung injury in dogs.

The intravenous administration of ethchlorvynol (ECV), in dogs, resulted in an acute lung injury (ALI) characterized by a 200 +/- 80% increase in venous admixture and a 142 +/- 30% increase in extravascular lung water (EVLW). Pretreatment with the cytochrome P-450 inhibitor 8-methoxypsoralen prevented the ECV-induced increase in venous admixture but not the increased EVLW. These findings parallel those reported for cyclooxygenase inhibition in ECV-induced ALI and suggest that an arachidonic acid (AA) metabolite of pulmonary cytochrome P-450 activity may mediate the increase in venous admixture of ALI. We demonstrate that canine pulmonary microsomes metabolize [1-(14)C]AA to a variety of products, including the cytochrome P-450 metabolites 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid (EET). In prostaglandin F2 alpha-contracted, isolated pulmonary venous rings, 5,6-EET induced relaxation in a concentration-dependent manner. This action of 5,6-EET was prevented by indomethacin (10(-5) M). These results suggest that may serve as the cyclooxygenase-dependent endogenous pulmonary vasodilator responsible for the increase in venous admixture of ECV-induced ALI.

Kinetics of pulmonary uptake of serotonin during exercise in dogs.

The multiple indicator-dilution technique was employed in the exercising dog to evaluate the effect of increasing activity on the pulmonary extraction and kinetics of removal of tracer 3H-labeled serotonin (5-HT) and on the measured central blood volume and tracer-accessible extravascular lung water. 51Cr-labeled red blood cells, 125I-labeled albumin, and 14C-labeled 1,8-octanediol were injected with labeled 5-HT at rest and at two increasing levels of exercise (lower and higher in 9 dogs). Blood flow approximately tripled at the highest level of exercise, and the central blood volume increased linearly with increasing blood flow. The tracer-accessible extravascular lung water increased in the transition from rest to low-level exercise and stabilized at an average proportion of 0.85 of the gravimetric extravascular lung water at the higher values of blood flow. The average labeled 5-HT extraction at rest was 42 +/- 11%, and this slowly decreased with increase in flow. The calculated permeability-surface area product for 5-HT increased approximately directly with increasing blood flow. We conclude that exercise results in an increase in the central blood volume that is accompanied by an increase in the tracer-accessible extravascular lung water (lung tissue recruitment) over low exercise levels, with no change at higher levels of exercise, and that the pulmonary capillary surface area subserving 5-HT uptake increases almost linearly with flow over the range of flows attained.

Effect of cyclooxygenase inhibition in a canine model of unilateral pulmonary occlusion and reperfusion

To assess the effects of the cyclooxygenase inhibitor diclofenac in a canine model of pulmonary occlusion and reperfusion of the left lower lobe (LLL). Twelve adult beagle dogs (13-17 kg) were randomly assigned to a control group (n = 6) and a diclofenac-treated group (n = 6). Animals in the treatment group received 20 mg diclofenac sodium/kg as a single dose both before the experiment and at the end of surgical preparation; six animals served as controls. In the anesthetized animals, the left upper and middle lobes were resected. Circulation and ventilation of the LLL were selectively blocked by clamping. Complete occlusion of the LLL (30 min) was followed by periods of selective reperfusion (10 min, RP) and combined reperfusion and reventilation (120 min, RP/RV). Reperfusion of the LLL resulted in a significant increase in pulmonary arterial pressure (Ppa) in the early RP/RV period as compared to baseline values (25.3 +/- 4.7 vs 15.8 +/- 1.9 mmHg, p < 0.05, paired t-test). This increase was significantly inhibited in the diclofenac-treated animals (17.0 +/- 2.0 mmHg, p < 0.01 vs controls, ANOVA). Gravimetrically determined extravascular lung water (EVLW) showed no significant difference in the continuously ventilated lobes of the right lung between diclofenac-treated animals (3.8 ml/g dry weight) and controls (3.9 +/- 0.9 ml/g dry weight) at the end of the experiment. EVLW, however, increased significantly in the LLL of control animals after 2 h of combined reperfusion and reventilation, whereas this increase was significantly inhibited in the diclofenac-treated animals (4.5 +/- 0.7 ml/g dry weight in the diclofenac group vs 6.5 +/- 1.3 ml/g dry weight in the control group, p < 0.05). Diclofenac inhibits the increase in both pulmonary arterial pressure and EVLW during reperfusion and reventilation of LLL. Thus, these changes appear to be mediated by cyclooxygenase metabolites.

Helium/Oxygen Breathing Improved Hypoxemia After Cardiac Surgery

Helium/Oxygen Breathing Improved Hypoxemia After Cardiac Surgery