Early treatment with pentoxifylline reduces lung injury induced by acid aspiration in rats.

Abstract

STUDY OBJECTIVES: To evaluate the effect of pentoxifylline treatment on gas exchange and mortality immediately after bilateral instillation of hydrochloric acid. DESIGN: Randomized, prospective, placebo-controlled trial. SETTING: Animal laboratory of a university hospital. SUBJECTS: Twenty-four, adult, male Sprague-Dawley rats. METHODS: Sevoflurane-anesthetized rats (n = 12 in each group) underwent tracheostomy and insertion of a cannula into a hind paw vein and the left carotid artery. All animals received volume-controlled mechanical ventilation (zero positive end-expiratory pressure; fraction of inspired oxygen, 0.21). Acute lung injury was induced by instillation of 0.4 mL/kg 0.1 mol/L hydrochloric acid. The animals were randomized into two groups. The pentoxifylline group (n = 12) received a bolus of 20 mg/kg IV pentoxifylline after aspiration, followed by a continuous infusion of 6 mg/kg/h. The placebo group (n = 12) received an equivalent volume of saline solution. Arterial blood samples were collected for blood gas analysis 15 min and 0 min prior to aspiration and 30, 90, 180, 270, and 360 min after aspiration. Hemodynamic parameters, temperature, and ECG were recorded simultaneously. The primary end point was 6 h after aspiration. All surviving rats were killed by IV administration of pentobarbital. To assess morphologic changes due to lung injury, all animals underwent CT in inspiratory hold at the end of the experiment. MEASUREMENTS AND RESULTS: No difference in baseline measurements was observed. In pentoxifylline-treated rats, Pao(2) was significantly increased (p < 0.05) at 30, 90, 180, 270, and 360 min. Mortality at 6 h was 17% in the pentoxifylline group vs 67% in the placebo group. Placebo-treated rats showed significant abnormalities in CT lung scans compared with the pentoxifylline group. CONCLUSIONS: Acid aspiration impairs gas exchange and induces hypotension. Pentoxifylline administration shortly after acid instillation results in significant alleviation of impaired oxygenation, stabilization of BP with higher heart rates, and improved survival after 6 h.