Pentoxifylline prevents a decrease in arterial oxygen tension in oleic acid-induced lung injury.
OBJECTIVE
a) To determine whether pentoxifylline has a preventive effect on the decrease in PaO2 that is caused by oleic acid, and whether pentoxifylline facilitates normalization of PaO2 from the decreased state. b) To examine whether pentoxifylline can attenuate an increase in pulmonary vascular permeability that is induced by oleic acid.


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
a) A total of 48 guinea pigs (700 to 1100 g) for blood gas analysis. b) A total of 28 guinea pigs (390 to 670 g) for measurement of pulmonary vascular permeability.


METHODS
a) For blood gas analysis, the guinea pigs were mechanically ventilated. Oleic acid (15 microL/kg) was injected into the guinea pigs to decrease PaO2. Pentoxifylline (5 or 20 mg/kg) was administered 40 or 3 mins before oleic acid injection or 13 mins after oleic acid injection. b) For measurement of pulmonary vascular permeability, the guinea pigs were anesthetized with pentobarbital and catheterized via the external jugular vein for drug administration. Pentoxifylline (20 mg/kg) plus Evans blue (30 mg/kg) or theophylline (20 mg/kg) plus Evans blue (30 mg/kg) were administered at 40- and 1-min intervals before oleic acid (15 microL/kg) injection, respectively. Perfusion with saline was performed through the aorta 90 mins after the oleic acid injection. The airways were removed and separated into the trachea, the main bronchus, the proximal bronchus, and the distal bronchus. Evans blue was extracted from the airways with formamide for 18 hrs and measured.


RESULTS
a) We measured PaO2, PaCO2, and pH, and recorded airway pressure and systemic blood pressure at 15, 10, and 5 mins before oleic acid injection and at 6, 10, 15, 35, 55, and 75 mins after oleic acid injection. Compared with the control groups, a decrease in PaO2 by oleic acid was significantly prevented when pentoxifylline (5 or 20 mg/kg) was administered 40 mins before oleic acid injection. However, a decrease in PaO2 by oleic acid was not significantly reduced when pentoxifylline was administered 3 mins before oleic acid injection. Pentoxifylline administered 13 mins after oleic acid injection did not affect the recovering course of PaO2 significantly. b) An increase in pulmonary vascular permeability by oleic acid was significantly attenuated by both pentoxifylline and theophylline. The effect of theophylline was significantly stronger than the effect of pentoxifylline in the main bronchi. The effect of theophylline was not significantly different from the effect of pentoxifylline in other areas.


CONCLUSIONS
Pentoxifylline is a noteworthy drug that could be a candidate as a therapy to help prevent hypoxemia in lung injuries that share a common mechanism with oleic acid-induced lung injury.
Moriuchi
H
H
Department of Pathopharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Yuizono
T
T
D000403:Airway Resistance; D000818:Animals; D001794:Blood Pressure; D002199:Capillary Permeability / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000517:prevention & control; D019301:Oleic Acid; D009829:Oleic Acids; D010100:Oxygen / Q000097:blood*; D010431:Pentoxifylline / Q000494:pharmacology*; D011446:Prospective Studies; D011652:Pulmonary Circulation; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D013806:Theophylline / Q000494:pharmacology
D009829:Oleic Acids; D002245:Carbon Dioxide; D019301:Oleic Acid; D013806:Theophylline; D010100:Oxygen; D010431:Pentoxifylline