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


METHODS
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.


CONCLUSIONS
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.
de Arruda
Marcio Jose Cristiano
MJ
Laboratory of Medical Investigation (LIM-62) of the Emergency Surgery Service, Hospital das Clinicas, São Paulo University Medical School--São Paulo/SP, Brazil.
Poggetti
Renato Sergio
RS
Fontes
Belchor
B
Younes
Riad N
RN
Souza
Almerindo Lourenço
AL
Birolini
Dario
D
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D004195:Disease Models, Animal; D007422:Intestines / Q000098:blood supply*; D008099:Liver / Q000098:blood supply*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000378:metabolism
D018721:Muscarinic Agonists; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride