Injection Of Oleic Acid Research Articles

Estimation of errors in determining intrathoracic blood volume using thermal dilution in pigs with acute lung injury and haemorrhage

Global end diastolic volume (GEDV) has a constant and predictable relationship to intrathoracic blood volume (ITBV). The present study assesses the difference between ITBV derived from GEDV and ITBV measured directly in pigs with acute lung injury (ALI) and mild haemorrhage. We caused ALI in 12 anaesthetized pigs by i.v. injection of oleic acid and removed 10% of estimated blood volume. EVLW, GEDV, ITBV (COLD; Pulsion Medical Systems), Pa(o(2))/Fi(o(2)), lung compliance and haemodynamic variables were measured at baseline (time 0) and at 30 and 120 min. All animals were volume-resuscitated, followed by measurements at 180 min. A linear equation estimated from the 44 pairs of ITBV and GEDV values in 11 animals was applied iteratively to the four GEDV measurements in the 12th animal, enabling 48 comparisons between measured (ITBVm) and derived ITBV (ITBVd) to be made. Increase in extravascular lung water index (EVLWi) was associated with significant pulmonary hypertension, worsening of oxygenation and compliance (repeated measures ANOVA; P<0.05). There was good within-subject correlation and agreement between ITBV(m) and ITBV(d) (r=0.72, mean bias 0.8 ml; sd 32 ml). Mean error in deriving ITBV from GEDV was 4.5%. (sd 4.2%; range 0.05-19%). There were no significant differences in errors in the presence of small (up to 10%) deficits in blood volume (F=1.0; P=0.41). ITBV estimated by thermodilution alone is comparable to measurements made by the thermo-dye dilution technique in the presence of pulmonary hypertension and mild deficits in total blood volume.

Oleic acid lung injury: a morphometric analysis using computed tomography.

The oleic acid-induced lung injury (OAI) model is considered to represent the early phase of acute respiratory distress syndrome (ARDS). Its inherent properties are important for the design and the interpretation of interventional studies. The aim of this study was to describe the evolution of morphometric lung changes during OAI using computed tomography (CT) analysis. Furthermore, the effect of a temporary change in positive end-expiratory pressure (PEEP) was evaluated. Fifteen anaesthetized pigs were ventilated in volume-controlled mode with a baseline PEEP of 5 cm H(2)O. Helical CT scans were taken at baseline and 1 h after oleic acid injection. The PEEP was then either increased to 10 cm H(2)O (n = 5), decreased to 0 cm H(2)O (n = 5) or kept constant (n = 5) for 30 min. For the next 30 min, the baseline PEEP level was applied in all animals before the final CT scans 2 h after the induction of OAI. Dimensional and volumetric changes were determined from radiographical attenuation values. There was a major decrease in gas volume and an increase in tissue volume within the first hour. A net increase in total lung volume, with a larger transverse area but no displacement of the diaphragm, was manifest after 2 h. A minor increase in volume of non-aerated lung, located to the caudal region, was observed during the second hour. The tidal volume was redistributed to the middle and apical regions. The temporary change in PEEP did not influence the morphological progress of OAI. Decreased gas volume and increased tissue volume are the dominating morphometric characteristics of oleic acid lung injury, occurring mainly within the first hour. With these changes manifest, the course of injury is not affected by a limited period of moderately changed PEEP during the second hour. The net increase of total lung volume suggests a predominance of oedema formation over airway and alveolar collapse.

Changes of carbon monoxide, nitric oxide levels and heme oxygenase system in acute respiratory distress syndrome induced by oleic acid

To investigate possible role of carbon monoxide (CO) and heme oxygenase (HO) in the pathogenesis of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) and to compared with that induced by nitric oxide (NO). ARDS model was established in rats by oleic acid injection and concentrations of CO and NO in pulmonary arterial, carotid jugular blood and bronchoalveolar lavage fluid (BALF) were measured sequentially. Immunohistochemical method was used to determine the expression of HO in the lung. Pulmonary arterial pressure in ARDS rats elevated 10 min after OA injection [(13.80 +/- 1.87) mm Hg to (19.51 +/- 5.02) mm Hg]. At 0.5 h after OA injection, concentration of CO in pulmonary artery began to increase and was markedly higher at 2 h than that in control rats [(0.135 +/- 0.010) g/L versus (0.116 +/- 0.005) g/L] (P < 0.01), also higher than that in carotid artery [(0.117 +/- 0.013) g/L] and in jugular vein [(0.107 +/- 0.018) g/L] in the same group, and maintained at a relatively high level thereafter. Concentration of CO in BALF also increased at 0.5 - 24 h and diminished at 72 h, as compared with that in controls. Concentration of NO in blood of pulmonary and systemic circulation all elevated markedly at 0.5 h and 2 h after OA injection, and then declined to normal at 12 h. Concentration of NO in BALF was significantly higher than that in controls. Arterial blood gas analysis showed that PaO2 markedly decreased in ARDS rats, especially at 2 h after OA injection. HO-2 could be expressed in the lung tissues of normal rats with immunohistochemical method, the strongest in epithelial cells of the bronchi, and HO-1 could only be expressed in pulmonary blood vessel walls, bronchial epithelial cells, alveolar epithelial cells and inflammatory cells of ARDS rats, lasting for 72 h after OA injection, consistent with that of CO level. ARDS rats showed a lastecl increase of CO level in pulmonary blood circulation, suggesting CO/HO system might play a more important role in modulation of blood vessel tension than NO might do in pathogenesis of ARDS.

Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water.

Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema. Prospective, randomized animal study. A university animal research laboratory. Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg. The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique. There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement. Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.

EFFECTS OF N-ACETYLCYSTEINE ON OXIDANT-ANTIOXIDANT BALANCE IN OLEIC ACID–INDUCED LUNG INJURY

The antioxidant and anti-inflammatory properties of N-acetylcysteine has been documented in many experimental lung injury models. Because intravenous injection of oleic acid induces histopathologic changes similar to those seen in human acute lung injury or acute respiratory distress syndrome, the authors evaluated the effects of N-acetylcysteine (NAC) on oxidative stress and lung damage in an oleic acid (OA)-induced lung injury model. Thirty-five rats were divided into 5 groups as sham, NAC, OA, pre-OA-NAC, and post-OA-NAC. Lung damage was induced by intravenous administration of oleic acid. Pre-OA-NAC group received intravenous (IV) N-acetylcysteine 15 minutes before oleic acid infusion and post-OA-NAC group received IV N-acetylcysteine 2 hours after oleic acid infusion. In both of the N-acetylcysteine treatment groups, blood and tissue samples were collected 4 hours after oleic acid infusion, independent from the time of N-acetylcysteine infusion. In other groups, blood and tissue samples were collected 4 hours after ethanol, NAC, or OA infusions. Serum myeloperoxidase activity, total antioxidant capacity, malondialdehyde levels, and lung tissue Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The administration of N-acetylcysteine significantly restored Na+-K+ ATPase activity and total antioxidant capacity levels and ameliorated lung architecture. N-acetylcysteine has been shown to have some attenuating effects in experimental animal studies. However, further investigations are necessary to suggest N-acetylcysteine as a treatment agent in critically ill patients with lung injury.

Preventive effect of tranilast on oleic acid-induced lung injury in guinea pigs.

Acute respiratory distress syndrome or acute lung injury (ARDS)/(ALI) involve the severe lung injury with pulmonary vascular hyper-permeability and hypoxemia induced by inflammatory reactions. Since ARDS/ALI carries high mortality, the development of new drugs against ARDS/ALI is required. We examined the effect of tranilast, an anti-allergic drug, on vascular hyper-permeability in the lungs and airways, and on hypoxemia, in oleic acid (OA)-induced acute lung injury, an animal model of ARDS/ALI. The increase in pulmonary and airway vascular permeability and the decrease in partial oxygen pressure of arterial blood induced by an intravenous injection of OA were drastically ameliorated by the oral administration of tranilast in a dose-dependent manner. This is the first report to prove that tranilast prevents pulmonary and airway vascular permeability and hypoxemia induced by OA. These results suggest that tranilast may be a candidate drug for the treatment of ARDS/ALI.

Effect of continuous hemofiltration on hemodynamics, lung inflammation and pulmonary edema in a canine model of acute lung injury.

This study examined whether continuous hemofiltration favorably affects cardiopulmonary variables, lung inflammation, and lung fluid balance in a canine model of oleic acid induced acute lung injury. Eleven pentobarbital-anesthetized dogs were randomly divided into a control (mechanical ventilation, MV) group (n=6) and a MV plus hemofiltration (HF) group (n=5). All animals received an intravenous injection of oleic acid (0.09 ml/kg) to induce acute lung injury. Continuous arterial-venous hemofiltration (blood flow 100 ml/min, ultrafiltration rate at 50-65 ml kg(-1) h(-1)) was started after establishment of oleic acid induced acute lung injury and continued for 4 h. Hemodynamics, lung mechanics, gas exchange, lung fluid balance, lung histology, and the level of plasma cytokines were assessed. After 240 min of HF treatment there was a significant increase in cardiac output, reduction in pulmonary arterial pressure, and improvement in both oxygenation and lung mechanics. Also, in the HF group the lung wet-to-dry weight ratio was significantly reduced. Histologically, HF reduced edema and inflammatory cell infiltration in the lung. There was also a significantly greater decrease in plasma IL-6 and IL-8 levels in the HF group than in group receiving MV alone. In a canine model of acute lung injury continuous HF improved cardiopulmonary function, reduced pulmonary edema, decreased lung permeability and inflammation, and decreased the plasma concentration of proinflammatory cytokines.

Regional Ventilation by Electrical Impedance Tomography: A Comparison With Ventilation Scintigraphy in Pigs

The validation of electrical impedance tomography (EIT) for measuring regional ventilation distribution by comparing it with single photon emission CT (SPECT) scanning. Randomized, prospective animal study. Animal laboratories and nuclear medicine laboratories at a university hospital. Twelve anesthetized and mechanically ventilated pigs. Lung injury was induced by central venous injection of oleic acid. Then pigs were randomized to pressure-controlled mechanical ventilation, airway pressure-release ventilation, or spontaneous breathing. Ventilation distribution was assessed by EIT using cross-sectional electrotomographic measurements of the thorax, and simultaneously by single SPECT scanning with the inhalation of (99m)Tc-labeled carbon particles. For both methods, the evaluation of ventilation distribution was performed in the same transverse slice that was approximately 4 cm in thickness. The transverse slice then was divided into 20 coronal segments (going from the sternum to the spine). We compared the percentage of ventilation in each segment, normalized to the entire ventilation in the observed slice. Our data showed an excellent linear correlation between the ventilation distribution measured by SPECT scanning and EIT according to the following equation: y = 0.82x + 0.7 (R(2) = 0.92; range, 0.86 to 0.97). Based on these data, EIT seems to allow, at least in comparable states of lung injury, real-time monitoring of regional ventilation distribution at the bedside.

Oxidative stress in early stage of acute lung injury induced with oleic acid in guinea pigs.

Changes in several biomarkers in bronchoalveolar lavage fluid (BALF) during an early stage of lung injury induced with oleic acid were examined in guinea pigs. In addition, a possible contribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase to the oxidative changes in the lung injury was investigated. An intravenous injection of oleic acid increased the levels of lipid peroxidation products, lactate dehydrogenase, and total proteins, decreased the ratio of glutathione to glutathione disulfide in the BALF, and also affected the levels of other oxidative biomarkers such as superoxide dismutase and catalase in the BALF in a dose-dependent manner. Diphenyleneiodonium chloride, a NADPH oxidase inhibitor, inhibited the oxidative changes in the BALF and the decrease in partial pressure of oxygen in artery induced with oleic acid, while allopurinol, a xanthine oxidase inhibitor, had no inhibitory effects. The results demonstrate that oxidative stress would be an important mechanism of oleic acid-induced lung injury, and indicate that the NADPH oxidase-dependent pathway contributes significantly to the generation of reactive oxygen species in oleic acid-induced lung injury.

Detection of porcine oleic acid-induced acute lung injury using pulmonary acoustics

To evaluate the utility of monitoring the sound-filtering characteristics of the respiratory system in the assessment of acute lung injury (ALI), we injected a multifrequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominantly in the dependent lung regions, increasing venous admixture from 6 +/- 1 to 54 +/- 8% (P < 0.05) and reducing dynamic respiratory system compliance from 19 +/- 0 to 12 +/- 2 ml/cmH(2)O (P < 0.05). A two- to fivefold increase in sound transfer function amplitude was seen in the dependent (P < 0.05) and lateral (P < 0.05) lung regions; no change occurred in the nondependent areas. High within-subject correlations were found between the changes in dependent lung sound transmission and venous admixture (r = 0.82 +/- 0.07; range 0.74-0.90) and dynamic compliance (r = -0.87 +/- 0.05; -0.80 to -0.93). Our results indicate that the acoustic changes associated with oleic acid-induced lung injury allow monitoring of its severity and distribution.

Ventilation-perfusion distributions in different porcine lung injury models.

Acute lung injury is characterized by hypoxemia which may be caused by hypoventilation, ventilation-perfusion (V(A)/Q) mismatch, intrapulmonary shunting and oxygen diffusion impairment. The multiple inert gas elimination technique (MIGET) allows analysis of these four causes of hypoxemia and is therefore the most comprehensive approach to investigate blood gas abnormalities. Using MIGET, we studied whether specific patterns of gas exchange abnormalities occur in different lung injury models and whether gas exchange abnormalities can be related to pathogenic aspects of lung injury. Lung injury was induced with oleic acid injection, endotoxin infusion or repeated lung lavage in groups of 6 mechanically ventilated pigs. PaO2 decreased and PaCO2 increased significantly in all three lung injury models, but gas exchange was more impaired in the oleic acid and lavage, as compared to the endotoxin group. Shunt was the major cause of hypoxemia in our lung injury models, whereas V(A)/Q mismatch contributed to venous admixture only after oleic acid injection and lung lavage. Oxygen diffusion limitation was not observed. Although alveolar ventilation was maintained after induction of lung injury, hypercapnia developed due to an increase of the ventilatory mean towards higher V(A)/Q ratios, increased shunt and increased carbon dioxide production. Shunt and ventilation-perfusion mismatch fully explain the gas exchange disturbances observed in our lung injury models. Although V(A)/Q distributions can be related to pathogenic aspects of the three study groups, we did not observe specific V(A)/Q patterns which allow diagnosis of the type of lung injury from a recovered V(A)/Q distribution.

Continuous versus pulsatile pulmonary hemodynamics in canine oleic acid lung injury.

Pulmonary hypertension occurs commonly in the acute respiratory distress syndrome (ARDS), but associated right ventricular failure is relatively rare. We tested the hypothesis that this apparent contradiction is explained by a peripheral location of the increased pulmonary vascular resistance (Rpva). Experimental ARDS was induced in eight dogs by injection of oleic acid (0.07 ml/kg). Changes in Rpva were evaluated by measurements of pulmonary artery pressure (Ppa) at several levels of flow (Q), which was altered by manipulation of venous return. The analysis of Ppa decay curves after arterial balloon occlusion was used to partition Rpva into arterial and venous segments. Right ventricular afterload was evaluated by determination of pulmonary vascular impedance (Zpva), which was calculated from spectral analysis of Ppa and Q waves. Oleic acid lung injury was associated with an increase in both the slope and the extrapolated pressure intercept of Ppa/Q plots, no change in the partitioning of Rpva, no change in time-domain indices in wave reflection or in pulmonary arterial compliance, and a decrease in both the characteristic impedance and pulsatile component of total right ventricular hydraulic load. We conclude that the site of increased Rpva in oleic acid lung injury is the smallest pulmonary arterioles, which, together with a decreased characteristic impedance, contributes to minimize right ventricular afterload.

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.

In vivo Hahn spin-echo decay (Hahn-T2) observation of regional changes in the time course of oleic acid lung injury.

We studied the time course of changes in the Hahn spin-echo decay (Hahn-T2) in lungs of spontaneously breathing living rats at 1 hour, 3 hours, and 7 days following oleic acid injection. Motion artifacts were minimized by using the motion-insensitive interleaved rapid line scan (ILS) imaging technique. Prior to injury, the lungs exhibited two resolvable exponential Hahn-T2 components. One and 3 hours after injury the decay showed a regionally nonuniform behavior, which was fit with one, two, or three exponential components. The short and medium components increased at 1 and 3 hours after injection. The third, much longer, component is probably due to intraalveolar pulmonary edema. After 7 days the Hahn decay was similar to that observed before injury, probably reflecting resolution of the edema. Our data suggest that Hahn-T2 measurements can be used to characterize the time course and regional distribution of lung injury in living animals.

Milrinone improves arterial oxygenation in dogs with acute lung injury induced by oleic acid.

The aim of the study was to investigate effects of milrinone on pulmonary permeability in dogs with acute lung injury induced by oleic acid. To induce acute lung injury, we administered 0.08 mg/kg of oleic acid to 19 adult mongrel dogs and then measured hemodynamic parameters and performed blood gas analysis. An injection of oleic acid depressed the mean arterial pressure, cardiac index, and arterial oxygenation. Dogs were divided into three groups: six received a bolus of milrinone (50 microg/kg) followed by a continuous (0.5 microg/kg/min, low-dose), seven received a bolus (100 microg/kg) followed by a continuous (1.0 microg/kg/min; i.e., a low-dose twice; high-dose), and six no milrinone (control). Milrinone administration improved the cardiac index and arterial oxygenation and simultaneously depressed the intrapulmonary shunt fraction and the extravascular thermal lung water as extravascular water content of the lung. These changes produced by milrinone are different according to the doses. In conclusion, milrinone acts on the capillary endothelium and inhibits an accumulation in the extravascular water content of the lung, which may induce an improvement in arterial oxygenation. Milrinone may also improve arterial oxygenation through an inhibition of platelet aggregation and chemical mediators that are released from platelets. The latter mechanism also may improve arterial oxygenation, and the exact property responsible for causing the effect of milrinone has not yet been identified.

The changes of plasma endothelin in oleic acid-induced acute lung injury and their implication.

The changes of pulmonary arterial and pulmonary venous plasma endothelin (ET) level in oleic acid (OA)--induced lung injury (ALI) rats were observed. After the ALI model of rats was established by intravenous injection of OA, blood samples were taken from a right cardiac catheter inserted via the right external jugular vein into the pulmonary artery to determine the plasma ET levels by using radioimmunoassay before OA injection, and 2 h and 4 h after OA injection. At the same time, arterial oxygen pressure (PaO2) and mean pulmonary arterial pressure (mPAP) were measured to evaluate the role of ET in acute lung injury. The results showed that the plasma ET levels after OA injection were significantly increased in OA group rats as compared with those in the controls, positively correlated with mPAP and negatively with PaO2. The plasma ET level in pulmonary vein was higher than in pulmonary artery, but no significant difference was found. It was concluded that ET, as a local or circulating hormone, might play an important role in pathophysiology of ALI.

Time domain reflectometry: measurement of free water in normal lung and pulmonary edema.

The free water content of lung tissue was investigated by dielectric spectroscopy in normal lungs and in pulmonary edema induced by oleic acid in rats. The dielectric relaxation in a frequency range of 10(7) to 10(10) Hz was measured with the time domain reflectometry method at 25 degreesC. Three dielectric relaxation processes were analyzed for the lung tissue. A high-frequency process around 10 GHz was attributed to the orientation of free water molecules based on the relaxation time [log tauh (in s) = -11.03]. The dielectric strength (Delta epsilon) of this high-frequency peak (Delta epsilonh) should reflect the amount of free water in the tissue. Because the measured Delta epsilonh depended on the air content of the lung samples, the value of Delta epsilonh was corrected for the air content of each sample as determined by the point-counting method in the area where the time domain reflectometry data were obtained. The lungs of rats that received an injection of oleic acid had a significantly increased free water content [(Delta epsilonh of lung/Delta epsilon of pure water) x density of pure water] compared with that in the normal lung (0.76 vs. 0.59 g/cm3). These results indicate that free water occupies approximately 60% of the total volume of normal lung tissue and that there is an increase in free water in pulmonary edema.

Neutrophil apoptosis during the development and resolution of oleic acid-induced acute lung injury in the rat.

The oleic acid (OA) model of acute lung injury in rats is characterized by a massive and rapid influx of polymorphonuclear neutrophils (PMN) within 1 h, with a peak inflammatory response at 4 h and resolution by 72 h. We hypothesized that PMN apoptosis is involved in the resolution of OA-induced acute lung injury. To test this hypothesis, healthy adult Fischer 344 rats were given 30 microl OA in 0.1% bovine serum albumin (BSA) intravenously; controls were given BSA alone and killed at 1, 4, 24, and 72 h after OA to obtain bronchoalveolar lavage fluid (BALF) and lung tissue. Cell pellets from BALF and formalin-fixed, paraffin-embedded tissue section samples were processed for terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) to identify apoptotic cells. Propidium iodide was used to counterstain nuclei. Percentage of nuclei undergoing apoptosis was counted under a fluorescent microscope. Control rats showed only resident alveolar macrophages (AM) in the BALF with no apoptosis. At the peak of injury, 1 h and 4 h after OA injection, we observed a massive PMN response without any evidence of apoptosis. At 24 h, when the OA injury is clinically and histologically in early resolution, we observed intense apoptosis of PMN nuclei along with evidence of apoptotic bodies in the cytoplasm of AM. Some of the AM also showed apoptotic nuclei at 72 h. Similar observations were made in the lung tissue sections. The results of the TUNEL assay were confirmed by DNA ladders and electron microscopy. We conclude that apoptosis of PMN and clearance by AM is an important mechanism in resolution of OA- induced acute lung injury.

Dynamics of lung collapse and recruitment during prolonged breathing in porcine lung injury.

Oleic acid (OA) injection, lung lavage, and endotoxin infusion are three commonly used methods to induce experimental lung injury. The dynamics of lung collapse and recruitment in these models have not been studied, although knowledge of this is desirable to establish ventilatory techniques that keep the lungs open. We measured lung density by computed tomography during breath-holding procedures. Lung injury was induced with OA, lung lavage, or endotoxin in groups of six mechanically ventilated pigs. After a stabilization period, repetitive computed tomography scans of the same slice were obtained during prolonged expirations with and without positive end-expiratory pressure and during prolonged inspirations after 5 and 30 s of expiration. Lung collapse and recruitment occurred mainly within the first 4 s of breath-holding procedures in all three lung injury models, and some collapse and recruitment occurred even within 0.6 s. OA-injured lungs were significantly more unstable than lungs injured by bronchoalveolar lavage or endotoxin infusion. In this experimental setting, expiration times <0.6 s are required to avoid cyclic alveolar collapse during mechanical ventilation without extrinsic positive end-expiratory pressure.

Amrinone improves right ventricular ejection fraction and oxygen delivery without deterioration of extravascular lung water in canine oleic acid pulmonary injury.

Fourteen mongrel dogs were anaesthetized and mechanically ventilated with oxygen. After oleic acid was administered intravenously, amrinone 1 mg/kg was intravenously administered to one group followed by a continuous infusion of 10 micrograms/kg/min for one hour (amrinone group, n = 7). Isovolumetric saline was administered to the control group (n = 7). Amrinone slightly lowered PaO2 but significantly increased oxygen delivery and improved gastric intramucosal pH (pHi) during the first 30 minutes (7.33 +/- 0.13) compared with the control group (7.21 +/- 0.06, P < 0.05). The pHi remained higher in the amrinone group (7.30 +/- 0.15) than in the control group (7.16 +/- 0.06, P < 0.05) after the drug was withdrawn. Extravascular lung water was significantly augmented after oleic acid injection and sustained in all animals for the remainder of the study.