lodoxamide-tromethamine and Pulmonary-Edema

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 micrograms/ml in right lung and 29 +/- 15 micrograms/ml in left lung (p less than 0.03); albumin concentration in right lung BAL of untreated animals was 1,180 +/- 319 micrograms/ml (p less than 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 greater than 0.65); PMN percentage in right BAL of untreated animals was 18.7 +/- 2.9 (p less than 0.001 vs. lodoxamide-treated animals).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amino Acids; Animals; Chemotaxis, Leukocyte; Histamine H1 Antagonists; Leukocyte Adherence Inhibition Test; Male; Neutrophils; Nitriles; Oxamic Acid; Pulmonary Edema; Rabbits; Therapeutic Irrigation; Tromethamine