A positron emission tomographic comparison of diffuse and lobar oleic acid lung injury

1988 ◽  
Vol 64 (6) ◽  
pp. 2357-2365 ◽  
Author(s):  
D. P. Schuster ◽  
J. W. Haller ◽  
M. Velazquez
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Dorsal Region ◽  
Lung Water ◽  
Positron Emission ◽  
Transcapillary Escape Rate ◽  
Severity Of Injury ◽  
Water Accumulation ◽  
The Right ◽  
Lung Lobes

We tested whether severity of injury measured from the pulmonary transcapillary escape rate for transferrin (PTCER), lung water accumulation, and changes in regional pulmonary blood flow (PBF) would be similar after oleic acid (OA) injection into either all lung lobes or directly into the pulmonary artery feeding the left caudal lobe (LCL) only. Measurements were made with positron emission tomography. After 0.015 ml/kg OA was injected into the LCL (Lobar, n = 5), lung water increased in the left dorsal region from 37 +/- 5 to 50 +/- 8 ml/100 ml lung (P less than 0.05), PTCER was 533 +/- 59 10(-4)/min, and regional PBF decreased 62%. No significant change occurred in the uninjured right dorsal lung where PTCER was 85 +/- 32. In the left ventral region PTCER was 357 +/- 60, PBF decreased only 31%, and the increase in lung water was less (25 +/- 3 to 30 +/- 6). In contrast after 0.08 ml/kg OA was injected via the right atrium (Diffuse, n = 6), PTCER (283 +/- 94) was lower in the left dorsal region of this group than in the corresponding region of the Lobar group (P less than 0.05). The increase in lung water, however, was the same, but no change occurred in PBF distribution. These results indicate important differences between the two methods of causing lung injury with OA. After injury lung water accumulates primarily in dependent portions of lung and is not always accompanied by a decrease in regional PBF. These decreases, when they occur, may instead indicate severe vascular injury.

Eicosanoid balance and perfusion redistribution of oleic acid-induced acute lung injury

1992 ◽  
Vol 73 (5) ◽  
pp. 2126-2134 ◽  
Author(s):  
A. H. Stephenson ◽  
A. J. Lonigro ◽  
S. W. Holmberg ◽  
D. P. Schuster
Keyword(s):  
Acute Lung Injury ◽  
Oleic Acid ◽  
Lung Injury ◽  
Water Concentration ◽  
Dependent Lung ◽  
Lung Water ◽  
Tissue Concentrations ◽  
Tissue Samples ◽  
Positron Emission ◽  
Regional Lung

We have proposed that endogenous prostacyclin opposes the vasoconstriction responsible for redistribution of regional pulmonary blood flow (rPBF) away from areas of increased regional lung water concentration (rLWC) in canine oleic acid- (OA) induced acute lung injury (D. P. Schuster and J. Haller. J. Appl. Physiol. 69: 353–361, 1990). To test this hypothesis, we related regional lung tissue concentrations of 6-ketoprostaglandin (PG) F1 alpha and thromboxane (Tx) B2 in tissue samples obtained 2.5 h after administration of OA (0.08 ml/kg iv) to rPBF and rLWC measured by positron emission tomography. After OA only (n = 16), rLWC increased in dependent lung regions. Some animals responded to increased rLWC by redistribution of rPBF away from the most edematous regions (OA-R, n = 6), whereas others did not (OA-NR, n = 10). In another six animals, meclofenamate was administered after OA (OA-meclo). After OA, tissue concentrations of 6-keto-PGF1 alpha were greater than TxB2 in all groups, but concentrations of 6-keto-PGF1 alpha were not different between OA-R and OA-NR animals. TxB2 was increased in the dependent regions of animals in both OA-R and OA-NR groups compared with controls (no OA, n = 4, P < 0.05). The tissue TxB2/6-keto-PGF1 alpha ratio was smaller in controls and OA-NR in which no perfusion redistribution occurred than in OA-R and OA-meclo in which it did occur. This TxB2/6-keto-PGF1 alpha ratio correlated significantly with the magnitude of perfusion redistribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of eicosanoid inhibition on the development of pulmonary edema after acute lung injury

1996 ◽  
Vol 80 (3) ◽  
pp. 915-923 ◽  
Author(s):  
D. P. Schuster ◽  
A. H. Stephenson ◽  
S. Holmberg ◽  
P. Sandiford
Keyword(s):  
Acute Lung Injury ◽  
Oleic Acid ◽  
Lung Injury ◽  
Pulmonary Edema ◽  
Experimental Models ◽  
Nuclear Medicine Imaging ◽  
Lung Water ◽  
Edema Formation ◽  
Cyclooxygenase Inhibition ◽  
Positron Emission

In experimental models of acute lung injury, cyclooxygenase inhibition improves oxygenation, presumably by causing a redistribution of blood flow away from edematous lung regions. This effect on perfusion pattern could also reduce alveolar edema formation. On the other hand, pulmonary pressures usually increase after cyclooxygenase inhibition, an effect that could exacerbate edema accumulation. Therefore we tested the following hypothesis: the total accumulation of pulmonary edema in dogs during a 24- to 28-h period of observation after acute lung injury caused by oleic acid will be less in a group of animals treated with meclofenamate (n = 6) or with the thromboxane-receptor blocker ONO-3708 (n = 5) than in a group of animals treated with oleic acid alone (placebo, n = 6). Lung water concentrations (LWC), the regional pattern of pulmonary perfusion, and protein permeability were measured with the nuclear medicine imaging technique of positron emission tomography. After 24-28 h, LWC was significantly less (P < 0.05) in the ONO-3708 group than in the meclofenamate group (a similar trend was seen compared with the placebo group, P = 0.12). After 24-28 h, pulmonary arterial pressures were highest in the meclofenamate group. Regardless of group, the only significant correlation with the change in LWC was with the integral of pulmonary pressures over the 24- to 28-h period. The data suggest that thromboxane inhibition will reduce edema accumulation in acute lung injury but that this effect depends on reducing as much as possible the simultaneous development of pulmonary hypertension from other causes.

scholarly journals Effects of Antibiotic Therapy on Pseudomonas aeruginosa-Induced Lung Injury in a Rat Model

1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Rat Model ◽  
In Vivo Model ◽  
Antibiotic Administration ◽  
Lung Water ◽  
Alveolar Epithelial ◽  
The Right

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.

scholarly journals Regional Gas Exchange and Cellular Metabolic Activity in Ventilator-induced Lung Injury

2007 ◽  
Vol 106 (4) ◽  
pp. 723-735 ◽  
Author(s):  
Guido Musch ◽  
Jose G. Venegas ◽  
Giacomo Bellani ◽  
Tilo Winkler ◽  
Tobias Schroeder ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Lung Injury ◽  
Metabolic Activity ◽  
Cell Activation ◽  
Test Lung ◽  
Ventilator Induced Lung Injury ◽  
Positron Emission ◽  
Cellular Metabolic Activity ◽  
The Right ◽  
Tissue Fraction

Background Alveolar overdistension and repetitive derecruitment-recruitment contribute to ventilator-induced lung injury (VILI). The authors investigated (1) whether inflammatory cell activation due to VILI was assessable by positron emission tomography and (2) whether cell activation due to dynamic overdistension alone was detectable when other manifestations of VILI were not yet evident. Methods The authors assessed cellular metabolic activity with [(18)F]fluorodeoxyglucose and regional gas exchange with [(13)N]nitrogen. In 12 sheep, the left ("test") lung was overdistended with end-inspiratory pressure of 50 cm H(2)O for 90 min, while end-expiratory derecruitment of this lung was either promoted with end-expiratory pressure of -10 cm H(2)O in 6 of these sheep (negative end-expiratory pressure [NEEP] group) or prevented with +10 cm H(2)O in the other 6 (positive end-expiratory pressure [PEEP] group) to isolate the effect of overdistension. The right ("control") lung was protected from VILI. Results Aeration decreased and shunt fraction increased in the test lung of the NEEP group. [(18)F]fluorodeoxyglucose uptake of this lung was higher than that of the control lung and of the test lung of the PEEP group, and correlated with neutrophil count. When normalized by tissue fraction to account for increased aeration of the test lung in the PEEP group, [(18)F]fluorodeoxyglucose uptake was elevated also in this group, despite the fact that gas exchange had not yet deteriorated after 90 min of overdistension alone. Conclusion The authors could detect regional neutrophil activation in VILI even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting.

Effect of endotoxin on oleic acid lung injury does not depend on priming

2001 ◽  
Vol 91 (5) ◽  
pp. 2047-2054 ◽  
Author(s):  
Daniel P. Schuster ◽  
James K. Kozlowski ◽  
Tim McCarthy ◽  
Jason Morrow ◽  
Alan Stephenson
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Low Dose ◽  
Flow Distribution ◽  
Biochemical Effects ◽  
Positron Emission ◽  
Biochemical Measurements ◽  
Gas Measurements ◽  
Oxidant Production ◽  
Physiological And Biochemical

Recent studies have demonstrated significant synergistic physiological and biochemical effects between low-dose endotoxin (Etx) administration and oleic acid (OA)-induced canine lung injury. To evaluate whether this interaction depends on Etx priming of some key cell population, we compared the effects of giving low-dose Etx both after as well as before inducing lung injury with OA. In addition to hemodynamic and blood-gas measurements, positron emission tomographic imaging was used to measure edema accumulation and intrapulmonary blood flow distribution. Biochemical measurements of the stable metabolites of prostacyclin and thromboxane were obtained as well as measurements of isoprostanes and reactive sulfhydryls as evidence for possible concomitant oxidant production. We found that the physiological and biochemical effects of low-dose Etx developed 30–45 min after its administration, regardless of whether Etx was administered before or after OA. No increase in either isoprostane or reactive sulfhydryl production after Etx and/or OA was detected. These data suggest that the synergistic effect of low-dose Etx and OA-induced lung injury is not due to a priming effect of Etx.

Simultaneous measurement of lung clearance rates for Tc- and In-DTPA in normal and damaged lungs

1989 ◽  
Vol 66 (5) ◽  
pp. 2293-2297 ◽  
Author(s):  
H. O'Brodovich ◽  
G. Coates ◽  
J. Kay ◽  
D. Muysson
Keyword(s):  
Oleic Acid ◽  
Lung Injury ◽  
Computer Assisted ◽  
Clearance Rates ◽  
Lung Water ◽  
Imaging Characteristics ◽  
Widespread Availability ◽  
Lung Water Content ◽  
Arterial Po2

We investigated the relative clearance rates for 99mTc-labeled diethylenetriamine-pentaacetate (Tc-DTPA) and 113mIn-labeled DTPA (In-DTPA) when they were inhaled and deposited together within the lungs of same animal. Submicronic aerosols containing Tc-DTPA and In-DTPA were simultaneously generated by different nebulizers and collected within the same anesthetic bag. The combined aerosols were insufflated into piglets. Clearances for both compounds were measured simultaneously in normal lungs and when the lungs were damaged by intravenous oleic acid or by a presumed oxidant agent, intravenous or intratracheal phorbol myristate acetate (PMA). A medium-energy collimator and a computer-assisted gamma camera were used to calculate clearances. Correction was made for downscatter from the In photopeak into the Tc window. Marked lung injury occurred as evidenced by increases in lung water content and decreases in arterial PO2. The clearance of In-DTPA was slightly but significantly slower than for Tc-DTPA in each group of animals. The correlation (r = 0.93) between clearances for Tc-DTPA and In-DTPA was good, even though in vitro studies demonstrated that Tc-DTPA, but not In-DTPA, slowly dissociated at room and body temperatures. Oleic acid increased, but surprisingly, PMA had no effect on clearance rates for both In-DTPA and Tc-DTPA. We recommend continued use of Tc-DTPA for these measurements in view of its lower cost, requirement for only low-energy collimation, better imaging characteristics, and widespread availability. The overlap between control and injured lungs and the lack of increased clearance rates after PMA suggest this technique does not always detect acute lung injury.

Effect of cyclooxygenase inhibition on ethchlorvynol-induced acute lung injury in dogs

1986 ◽  
Vol 61 (3) ◽  
pp. 1058-1064 ◽  
Author(s):  
R. S. Sprague ◽  
A. H. Stephenson ◽  
T. E. Dahms ◽  
A. J. Lonigro
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Reactivity ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase Inhibitors ◽  
Lung Water ◽  
Edema Formation ◽  
Cyclooxygenase Inhibition ◽  
Cyclooxygenase Activity ◽  
The Right

In anesthetized dogs ethchlorvynol (ECV, 9 mg/kg) was selectively administered into the right pulmonary circulation to produce unilateral acute lung injury (ALI) characterized by nonhydrostatic pulmonary edema and systemic hypoxemia. To investigate the hypothesis that products of cyclooxygenase activity are mediators of the arterial hypoxemia, but not the edema formation in this injury, animals were pretreated with one of two chemically dissimilar cyclooxygenase inhibitors, indomethacin (5 mg/kg), or ibuprofen (12.5 mg/kg), or vehicle (0.1 M sodium carbonate) prior to the administration of ECV. Pretreatment with either inhibitor prevented the ECV-induced systemic hypoxemia observed in animals pretreated with vehicle (P less than 0.01). Despite this protection of systemic oxygenation, there was no redistribution of blood flow to the uninjured lung following unilateral ECV administration. Cyclooxygenase inhibition prior to ALI did not attenuate the accumulation of lung water. In the ibuprofen group, left atrial pressure increased significantly following ECV administration. We conclude that a product(s) of cyclooxygenase-mediated arachidonic acid metabolism is responsible for the altered vascular reactivity and consequent systemic hypoxemia in this model, but that the edema formation following ECV is not related to cyclooxygenase activity. In addition, ibuprofen, administered prior to the induction of ALI, exhibits properties not shared by indomethacin but is not different in its capacity to attenuate hypoxemia or in its failure to limit edema formation.

scholarly journals Ventilation inhomogeneity in oleic acid-induced pulmonary edema

1997 ◽  
Vol 82 (4) ◽  
pp. 1040-1045 ◽  
Author(s):  
John Y. C. Tsang ◽  
Michael J. Emery ◽  
Michael P. Hlastala
Keyword(s):  
Oleic Acid ◽  
Pulmonary Edema ◽  
Phase Iii ◽  
Lung Water ◽  
Peripheral Airways ◽  
Ventilation Inhomogeneity ◽  
Distal Airway ◽  
Tissue Compliance ◽  
Permeability Pulmonary Edema ◽  
The Right

Tsang, John Y. C., Michael J. Emery, and Michael P. Hlastala. Ventilation inhomogeneity in oleic acid-induced pulmonary edema. J. Appl. Physiol.82(4): 1040–1045, 1997.—Oleic acid causes permeability pulmonary edema in the lung, resulting in impairment of gas-exchange and ventilation-perfusion heterogeneity and mismatch. Previous studies have shown that by using the multiple-breath helium washout (MBHW) technique, ventilation inhomogeneity (VI) can be quantitatively partitioned into two components, i.e., convective-dependent inhomogeneity (cdi) and diffusive-convective-dependent inhomogeneity (dcdi). Changes in VI, as represented by the normalized slope of the phase III alveolar plateau, were studied for 120 min in five anesthetized mongrel dogs that were ventilated under paralysis by a constant-flow linear motor ventilator. These animals received oleic acid (0.1 mg/kg) infusion into the right atrium at t = 0. MBHWs were done in duplicate for 18 breaths every 40 min afterward. Three other dogs that received only normal saline served as controls. The data show that, after oleic acid infusion, dcdi, which represents VI in peripheral airways, is responsible for the increasing total VI as lung water accumulates progressively over time. The cdi, which represents VI between larger conductive airways, remains relatively constant throughout. This observation can be explained by increases in the heterogeneity of tissue compliance in the periphery, distal airway closure, or by decreases in ventilation through collateral channels.

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