Acute Portal Hypertension Increases Ileal Vulnerability to Platelet-Activating Factor in Rats

Abstract

Background. Patients with portal hypertension can easily develop sepsis of enteric origin after suffering severe trauma and hemorrhagic shock. Platelet-activating factor (PAF) is one of the key mediators of such stress. The aim of this study was to investigate whether portal hypertension increases the vulnerability of the ileum to PAF.Materials and methods. Seven days after surgery, PAF (1.5 μg/kg) was intravenously injected into portal stenosis (PS) rats and sham-operated rats. The levels of tumor necrosis factor-α (TNF-α), cytokine-induced neutrophil chemoattractant (CINC), and endotoxin in portal plasma were determined. The levels of PAF receptor (PAFR), TNF-α, and CINC mRNA in the ileum were also investigated.Results. After PAF administration, PS rats showed (1) significantly higher portal plasma levels of TNF-α, CINC, and endotoxin; (2) higher histological damage scores in the ileum; (3) more infiltrating neutrophils in the ileum; and (4) a significantly higher mortality rate than sham-operated rats (P < 0.01). However, PAFR mRNA levels were similar in the two groups. The CINC mRNA level in the ileum of PS rats was increased from 1 to 4 h after PAF administration, while that of the sham-operated rats was transiently increased at 1 h.Conclusions. Portal hypertension increases the vulnerability of the ileum to PAF. These findings suggest that conditions which causes PAF production may be dangerous in patients with portal hypertension.