Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema

C. F. Veal, Robert Jackson, A. L. Brannen, J. D. Fulmer

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 ± 165 μg/ml in right lung and 29 ± 15 μg/ml in left lung (p < 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 ± 319 μg/ml (p < 0.02 vs. lodoxamide-treated animals). PMN percentages in right BAL (3.8 ± 3.1) and left BAL (2.9 ± 2.2) did not differ in lodoxamide-treated animals (p > 0.65); PMN percentage in right BAL of untreated animals was 18.7 ± 2.9 (p < 0.001 vs. lodoxamide-treated animals). Incubation of PMNs of lodoxamide (1, 10, and 100 μg/ml) resulted in a dose-dependent decrease in directed migration (p < 0.005) but did not affect PMN adherence. Wet/dry weight ratio was not affected by lodoxamide administration. Thus, lodoxamide prevents PMN influx and decreases the alveolar-capillary protein leak in RPE, primarily by inhibiting PMN chemotaxis.

Original languageEnglish
Pages (from-to)227-232
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume14
Issue number2
StatePublished - Jan 1 1989
Externally publishedYes

Fingerprint

Pulmonary Edema
Neutrophils
Lung
Dimercaprol
Oxygen
Rabbits
Weights and Measures
Chest Tubes
Acute Lung Injury
Poisons
Therapeutic Irrigation
Chemotaxis
Pentobarbital
lodoxamide ethyl
lodoxamide tromethamine
Reperfusion
Albumins
Myocardium
Air
Pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema. / Veal, C. F.; Jackson, Robert; Brannen, A. L.; Fulmer, J. D.

In: Journal of Cardiovascular Pharmacology, Vol. 14, No. 2, 01.01.1989, p. 227-232.

Research output: Contribution to journalArticle

@article{d013f2e4613d412c9971d01523784d46,
title = "Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema",
abstract = "Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 ± 165 μg/ml in right lung and 29 ± 15 μg/ml in left lung (p < 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 ± 319 μg/ml (p < 0.02 vs. lodoxamide-treated animals). PMN percentages in right BAL (3.8 ± 3.1) and left BAL (2.9 ± 2.2) did not differ in lodoxamide-treated animals (p > 0.65); PMN percentage in right BAL of untreated animals was 18.7 ± 2.9 (p < 0.001 vs. lodoxamide-treated animals). Incubation of PMNs of lodoxamide (1, 10, and 100 μg/ml) resulted in a dose-dependent decrease in directed migration (p < 0.005) but did not affect PMN adherence. Wet/dry weight ratio was not affected by lodoxamide administration. Thus, lodoxamide prevents PMN influx and decreases the alveolar-capillary protein leak in RPE, primarily by inhibiting PMN chemotaxis.",
author = "Veal, {C. F.} and Robert Jackson and Brannen, {A. L.} and Fulmer, {J. D.}",
year = "1989",
month = "1",
day = "1",
language = "English",
volume = "14",
pages = "227--232",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Lodoxamide tromethamine prevents neutrophil accumulation in reexpansion pulmonary edema

AU - Veal, C. F.

AU - Jackson, Robert

AU - Brannen, A. L.

AU - Fulmer, J. D.

PY - 1989/1/1

Y1 - 1989/1/1

N2 - Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 ± 165 μg/ml in right lung and 29 ± 15 μg/ml in left lung (p < 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 ± 319 μg/ml (p < 0.02 vs. lodoxamide-treated animals). PMN percentages in right BAL (3.8 ± 3.1) and left BAL (2.9 ± 2.2) did not differ in lodoxamide-treated animals (p > 0.65); PMN percentage in right BAL of untreated animals was 18.7 ± 2.9 (p < 0.001 vs. lodoxamide-treated animals). Incubation of PMNs of lodoxamide (1, 10, and 100 μg/ml) resulted in a dose-dependent decrease in directed migration (p < 0.005) but did not affect PMN adherence. Wet/dry weight ratio was not affected by lodoxamide administration. Thus, lodoxamide prevents PMN influx and decreases the alveolar-capillary protein leak in RPE, primarily by inhibiting PMN chemotaxis.

AB - Reexpansion pulmonary edema (RPE) is an acute, unilateral lung injury initiated by cytotoxic oxygen metabolites and temporally associated with an influx of polymorphonuclear neutrophils (PMNs); these toxic oxygen products appear to result from reoxygenation of chronically collapsed lung. Lodoxamide tromethamine (U-42585E) reduces infarct size after reperfusion of ischemic myocardium. The possible protective effects of lodoxamide in RPE were examined. Right lungs of rabbits were collapsed for 7 days by injection of air into the pleural space. Reexpansion was accomplished by chest tube with negative pressure in spontaneously ventilating rabbits. Twelve pairs of animals received either lodoxamide (20 mg/kg/h intravenously (i.v.) from 30 min before reexpansion until they were killed) or an equivalent volume of sterile saline. After 2 h, animals were killed by i.v. pentobarbital. Right and left lungs of six pairs of animals were lavaged with 25 ml saline each; the remaining six pairs of animals were studied by measurement of lung wet/dry weight ratio. Albumin concentrations in lavage fluid (BAL) of lodoxamide-treated animals were 243 ± 165 μg/ml in right lung and 29 ± 15 μg/ml in left lung (p < 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 ± 319 μg/ml (p < 0.02 vs. lodoxamide-treated animals). PMN percentages in right BAL (3.8 ± 3.1) and left BAL (2.9 ± 2.2) did not differ in lodoxamide-treated animals (p > 0.65); PMN percentage in right BAL of untreated animals was 18.7 ± 2.9 (p < 0.001 vs. lodoxamide-treated animals). Incubation of PMNs of lodoxamide (1, 10, and 100 μg/ml) resulted in a dose-dependent decrease in directed migration (p < 0.005) but did not affect PMN adherence. Wet/dry weight ratio was not affected by lodoxamide administration. Thus, lodoxamide prevents PMN influx and decreases the alveolar-capillary protein leak in RPE, primarily by inhibiting PMN chemotaxis.

UR - http://www.scopus.com/inward/record.url?scp=0024314453&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024314453&partnerID=8YFLogxK

M3 - Article

C2 - 2476595

AN - SCOPUS:0024314453

VL - 14

SP - 227

EP - 232

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 2

ER -