Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats.

INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF)- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia), or sham procedures (control), followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10(-7) to 3 x 10(-4)) was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue) showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL) concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains to be determined.

Lung microvascular permeability and neutrophil recruitment are differently regulated by nitric oxide in a rat model of intestinal ischemia-reperfusion.

We investigated the effect of two inhibitors of nitric oxide (NO) synthesis, N(w)-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, on lung inflammation caused by intestinal ischemia/reperfusion in rats. Relative to the sham-operated rats, intestinal ischemia/reperfusion (ischemia: 45 min; reperfusion: 30 min, 2 and 4 h) induced neutrophil recruitment (increased myeloperoxidase activity) and increased microvascular permeability (Evans blue dye extravasation) in the lungs and increased tumor necrosis factor (TNF) levels in the serum (L-929 cytotoxicity assay). L-NAME given before the ischemia exacerbated neutrophil accumulation, plasma extravasation, serum TNF and caused death of the animals, which was prevented by concomitant injection of L-arginine. Lung and systemic effects of intestinal ischemia/reperfusion were not modified when L-NAME was given just before reperfusion. Treatment with aminoguanidine inhibited plasma extravasation without affecting the other parameters evaluated. Dexamethasone reduced all the parameters. Our results indicate that during intestinal ischemia/reperfusion both constitutive and inducible NO synthases are called to exert a differential modulatory effect on lung inflammation and that maintenance of adequate levels of NO during ischemia is essential for the animals survival.