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

Abstract

INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF)- α 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-α levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-α 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 × 10-4) was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-α 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-α (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-α increase, but whether the increase in TNF-α caused this bronchial contractility remains to be determined.