Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of three different doses (15, 20, and 25 mg/kg) of Perilla ketone (PK) on the blood-perfused in situ sheep lung while obtaining external measurements of lung transvascular protein flux. Lymph flow and lymphatic protein clearance increased significantly after all doses of PK. Severe pulmonary edema was confirmed by high postmortem wet-to-dry lung weight ratios and increased extravascular lung water from multiple indicator-dilution studies. Urea permeability-surface area product and effective diffusivity from multiple indicator-dilution studies also increased after PK infusion. Because we observed no evidence of increased capillary pressure or increased microvascular surface area after PK, we conclude that PK significantly increased pulmonary microvascular permeability. Certain aspects of the in situ PK response appeared to be dose dependent. The lungs responded rather quickly to high doses of PK, but an apparent latency period was noted with low doses of PK. Postmortem wet-to-dry lung weight ratios were always high but did not suggest dose dependence. However, times of postmortem measurements were not the same for all doses of PK. The external scan technique appeared to be sensitive to changes that occurred in the lung after PK. Externally detected albumin interstitial-to-plasma mass (mass I/P) ratios were substantially higher after PK than during control in situ studies. In some experiments, final mass I/P ratios increased above 4 approximately 2.0 h after PK compared with control values of 0.2 and 0.4. A delay time between injection and change in mass I/P slope was also observed, which decreased with increasing dose of PK. PK causes a permeability injury in the in situ sheep lung and provides a useful model for studying the sensitivity of permeability measurement techniques such as the external gamma-ray detection method.
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PMID:Effects of Perilla ketone on the in situ sheep lung. 155 25

A single infusion of Perilla ketone (PK) into sheep causes marked increases in lung fluid and solute exchange in the absence of any alteration in either pulmonary arterial or left atrial pressures. These alterations are most compatible with increased pulmonary microvascular permeability. The present paper describes the morphologic changes that accompany the previously described alterations in lung function. In five anesthetized open-chest sheep, lung biopsy tissue was taken at baseline and at 15, 30, 60, 120, and 180 minutes after the start of a single infusion of PK (15-20 mg/kg given over a 20 minute period). Biopsy tissue was taken from different lobes of the lung in random sequence, fixed, and processed for light and electron microscopic examination. Three control sheep received the vehicle, dimethyl sulfoxide, alone. Just 15 minutes after the start of PK infusion, alveolar capillary congestion, accumulation of peripheral lung neutrophils, and intraalveolar and interstitial edema were apparent. Electron microscopy revealed early evidence of damage to both the microvascular endothelial cells and Type I pneumonocytes. The damage became more severe with time. From 30 minutes, occasional nonciliated cells in the airway epithelium exhibited dilated rough and agranular endoplasmic reticulum. Thus, PK causes rapid onset of pulmonary edema accompanied by structural evidence of damage to the microvascular endothelium and Type I pneumonocytes. Pulmonary inflammation was also evident. These structural changes occur before the described alterations in either pulmonary microvascular permeability or reduction in pulmonary compliance.
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PMID:Morphology of noncardiogenic pulmonary edema induced by Perilla ketone in sheep. 318 7

We designed a series of experiments to compare the pulmonary dysfunction observed in models of cardiogenic and noncardiogenic pulmonary edema in chronically instrumented awake sheep. Cardiogenic pulmonary edema was induced by inflating the balloon of a Foley catheter surgically positioned in the mitral valve orifice causing increased left atrial pressure (increases PLA). Noncardiogenic pulmonary edema was induced by intravenous infusion of Perilla ketone (PK). Calculated microvascular pressure remained constant during PK infusion but increased from 9.4 +/- 0.7 to 42.8 +/- 2.4 cm H2O during increases PLA. Comparable increases in lung lymph flow (QL) were observed in the two protocols (five to seven times baseline). Pulmonary edema as quantified by chest radiograph scores increased from 0 (normal) to 2.9 +/- 0.5 and 3.4 +/- 0.1 in the PK and increases PLA groups, respectively. Room air alveolar to arterial oxygen pressure difference (P[A-a]O2) increased from 24 +/- 3 to 46 +/- 7 mm Hg in the PK group and from 23 +/- 4 to 56 +/- 6 mm Hg in the increases PLA group. Dynamic compliance of the lungs (Cdyn) expressed as the percentage of the baseline value decreased to 53 +/- 7 and 50 +/- 7% in the PK and increases PLA groups, respectively. Resistance to airflow across the lungs (RL) increased from 2.5 +/- 0.6 to 3.3 +/- 0.8 cm H2O.L-1.sec-1 in the PK group and from 1.4 +/- 0.3 to 4.2 +/- 1.1 in the increases PLA group. Significant correlations were observed between changes in the severity of pulmonary edema observed on chest radiographs, Cdyn, delta P(A-a)O2, and QL in both the increases PLA groups. We conclude that similar degrees of pulmonary edema, regardless of the mechanism, are associated with similar changes in QL, Cdyn, and delta P(A-a)O2. Hydrostatic pulmonary edema appeared to cause greater changes in RL than that resulting from increased microvascular permeability.
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PMID:Comparison of the pulmonary dysfunction caused by cardiogenic and noncardiogenic pulmonary edema. 765 36

Perilla ketone (PK) is a potent lung toxin that causes increased microvascular permeability pulmonary edema in grazing animals. Because the mechanism of action of PK is not know, we investigated whether PK directly affects endothelial cells. Bovine aortic endothelial cells were grown to confluence on Cytodex-3 microcarrier beads and placed in a chromatographic cell column. Monolayer permeability was evaluated from the elution profiles of three optical tracers: blue dextran (2 x 10(6) mol wt), sodium fluorescein (NaF, 342 mol wt), and cyanocobalamin (B12, 1,355 mol wt). Perfusion with 1.2 mM PK increased permeability within 15 min to NaF and B12 by 51 +/- 6 and 54 +/- 11%, respectively. Permeability returned to baseline after PK removal. These in vitro results suggest that PK produces a rapid and reversible increase in endothelial permeability directly. Staining of fixed cells with rhodamine-phalloidin revealed a major disruption of actin microfilaments after PK treatment. Because previous reports suggested that PK may be activated via cytochrome P-450, we attempted to block this using the cytochrome P-450 inhibitor ketoconazole. Ketoconazole alone did not significantly affect permeability, and the combination of PK and ketoconazole resulted in permeability increases similar to those measured for PK alone. This suggests that PK may not require cytochrome P-450 to increase vascular permeability.
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PMID:Perilla ketone increases endothelial cell monolayer permeability in vitro. 768 99

To determine whether the severity of the pulmonary edema in sheep models of cardiogenic and non-cardiogenic pulmonary edema correlate with concomitant alterations in airway responsiveness using three separate measures of pulmonary edema: post-mortem wet-to-dry lung weight ratio (W/D), chest radiograph (CXR) scores, and small airway wall area. Cardiogenic pulmonary edema was induced by increasing left atrial pressure (increase PLA) and non-cardiogenic pulmonary edema was induced by intravenous administration of Perilla ketone (PK). There was a significant negative correlation between changes in airway responsiveness and changes in CXR grade (r=-0.749, P<0.05), W/D (r=-0.662, P<0.05), airway wall areas (r=0.784, P<0.05) after increases in both PLA and PK. Chest radiograph score, W/D, and airway wall area correlated with each other (CXR score and W/D r=0.657, P<0.05; CXR score and airway wall area r=0.678, P<0.05; airway wall area and W/D r=0.704, P<0.05). We speculate that the increased airway responsiveness observed during pulmonary edema may result from the mechanical effects of edema formation within the airways.
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PMID:Correlation between increased airway responsiveness and severity of pulmonary edema. 1116 19