Effect of speed of rewarming and administration of anti-inflammatory or anti-oxidant agents on acute lung injury in an intestinal ischemia model treated with therapeutic hypothermia.

Abstract

Acute lung injury (ALI) develops in various clinical situations and is associated with high morbidity and mortality and therapeutic hypothermia (HT) has been studied to attenuate the ALI. However, the optimal method of rewarming has not been determined. We determined the effect of speed of rewarming and the administration of anti-inflammatory or anti-oxidant agents on ALI in an intestinal ischemia and reperfusion (I/R) model treated with HT. A Sprague-Dawley rat model of intestine ischemia and reperfusion was used. Two parallel animal experiments were conducted. In the survival study, rats (n=5 per group) underwent normothermic intestinal ischemia (60min, 36-38 degrees C) and then randomized into 7 groups with reperfusion: normothermia (NT), HT without rewarming (30-32 degrees C, HT), 2h HT+rewarming for 1h (RW1), 2h HT+rewarming for 2h (RW2), RW1+N-acetyl cysteine (RW-NAC), RW1+ethylpyruvate (RW-EP), and RW1+dexamethasone (RW+Dexa). In the second experiment, we investigated the histological and biochemical effects on the lung 4h after reperfusion (n=8 per group). The survival rate was lowest after NT. The HT, RW2, and RW-Dexa groups survived longer than the RW1, RW-NAC, and RW-EP groups. ALI scores were lower in the HT, RW2, and RW-Dexa groups than RW1. Lung malondialdehyde content was also lower in these groups. Interleukin (IL)-6 was significantly higher in the RW1 group. Inducible NO synthase gene expression in lung was lower in the HT, RW2, and RW-Dexa than RW1, and serum NO was lower in the RW2 and RW-Dexa than RW1. Gradual rewarming and administration of dexamethasone improved survival and attenuated ALI after intestinal I/R injury treated with HT in rats.