Prediction of reversibility of intestinal mucosal damage after ischemia-reperfusion injury by plasma intestinal fatty acid-binding protein levels in pigs

Abstract

Objective: The aims of this study were to elucidate the association between plasma intestinal fatty acid-binding protein (I-FABP) level and actual pathological damage of intestinal mucosa and its reversibility. Methods: An intestinal ischemia-reperfusion model was created by temporary occlusion of the descending aorta in 9 pigs which were divided into 3 groups according to the duration of visceral ischemic insult: 15-minute ischemia (n=3), 30-minute ischemia (n=3) and 60-minute ischemia (n=3). Blood samples and short segments of the jejunum for pathological examinations, including immunohistochemical staining of I-FABP, Ki-67 and E-cadherin, were taken at the beginning of the operation (T1) and 15 minutes (T2), 30 minutes (T3), 45 minutes (T4) and 60 minutes (T5) after reperfusion. Results: Plasma I-FABP after 15 minutes of ischemia reached a peak of 1859±1089 pg/ml at T3, while the level after 30 minutes of ischemia achieved a peak level of 5053±1717 pg/ml at T5. The level after 60 minutes of ischemia demonstrated a rapid increment up to 10734±93 pg/ml at T3. There was a significant difference in the trend of plasma I-FABP levels between 30 minutes and 60 minutes of ischemia (p=0.01). The strongest immunohistochemical staining of the intestinal epithelium for I-FABP was observed at T4 after 30 minutes of ischemia, with the shedding of injured epithelium followed by re-epithelialisation, with sequential up-regulation of Ki67 and E-cadherin. However, the intestinal epithelium after 60 minutes of ischemia demonstrated the lack of I-FABP expression with irreversible damage. Conclusion: Plasma I-FABP levels may be a crucial marker to recognize the reversibility of damage of the intestinal epithelium after an ischemic insult and the level of 5000 pg/ml is considered to be the critical borderline for irreversibility, which might prevent diagnostic delay in the clinical setting.