Chest
Volume 127, Issue 2, February 2005, Pages 613-621
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Laboratory and Animal Investigations
Early Treatment With Pentoxifylline Reduces Lung Injury Induced by Acid Aspiration in Rats

https://doi.org/10.1378/chest.127.2.613Get rights and content

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, Pao2 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.

Section snippets

Anesthesia, Fluid Balance, Monitoring

The local Bioethics Committee approved the experimental protocol for this study. Twenty-four, adult, male Sprague-Dawley rats weighing 280 to 320 g (Charles River; Sulzfeld, Germany) were cared for and handled according to the guidelines of the German National Institute of Health. On arrival at our facility, all rats received food and water ad libitum. Anesthesia was induced in a 2-L container and maintained by inhalation of an inspired concentration of 2.5% sevoflurane, tracheostomy was

Blood Gas Analysis

The Pao2 values and arterial gas analyses are summarized in Figure 1. There were no differences between the groups in the baseline measurements 15 min and immediately prior to tracheal acid instillation. As expected, the Pao2 showed an initial decline in both groups 30 min after acid instillation. At this time point, the Pao2 did not differ significantly between groups, although the placebo group had a mean Pao2 15 mm Hg lower than the pentoxifylline-treated animals. While Pao2 almost returned

Discussion

Although several experimental studies1415 have demonstrated that pentoxifylline has beneficial effects on lung inflammation and may result in decreased lung injury, the effect of early treatment on pulmonary function and hemodynamic parameters after an aspiration event has not been previously reported. Aspiration of gastric components leads to activation of macrophages and release of proinflammatory cytokines such as TNF-α, which is followed by neutrophil infiltration into the interstitial and

Conclusions

Acid aspiration impairs gas exchange and induces hypotension. These data suggest that early treatment with pentoxifylline effectively improves oxygenation, markedly stabilizes systemic hemodynamics, and results in better survival after 6 h in a model of acid aspiration-induced lung injury.

ACKNOWLEDGMENT

The authors thank David Tracey, PhD, Department of Anatomy, University of New South Wales, Sydney, Australia for helpful comments regarding this manuscript.

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