Induction of endotoxin tolerance improves lung function after warm ischemia in dogs

Abstract

In shock models, induction of endotoxin tolerance (ET) is known to have a protective effect. The present study was designed to explore if ET is effective in protecting lungs from reperfusion injury. Twelve foxhounds were used as experimental animals. After a left thoracotomy, the left hilum was clamped for 3 h, followed by 8 h of reperfusion. In the treatment group (ET, n = 6), dogs were pretreated with incremental daily endotoxin doses of up to 60 μg/kg on day 6. The ischemia and reperfusion experiment was carried out on day 9. Control group animals ( n = 6) were not subjected to endotoxin. After 8 h of observation, functional parameters of the reperfused lung of the ET and the control group were statistically different ( P < 0.05) with respect to Po2[ET vs. control: 172.7 ± 12.9 vs. 66.1 ± 7.2 (SE) mmHg], compliance (16.0 ± 1.2 vs. 8.3 ± 1.0 ml/0.1 kPa), and the wet-to-dry ratio (9.4 ± 0.8 vs. 16.7 ± 1.2). After 3 h of warm ischemia and 8 h of reperfusion, pulmonary function and lung water content improved in the endotoxin-tolerant group.