Gut macromolecular permeability in pancreatitis correlates with severity of disease in rats

Background: Increased intestinal macromolecular permeability could allow absorption of substances from the bowel into the systemic circulation and contribute to multiple organ system failure. Methods: Mild, intermediate, and severe grades of pancreatitis were induced in rats using intravenous caerulein and intraductal glycodeoxycholic acid. [¹⁴C]polyethylene glycol (molecular weight, 3350 daltons; 1.1 μCi/142 mg) was instilled into the distal duodenum. At 24 hours, the animals were killed, ascitic fluid was collected for trypsinogen activation peptide measurement, and pancreatic specimens were collected and scored for based on the degree of necrosis, inflammation, and hemorrhage. Results: Gut permeability to polyethylene glycol 3350 (PEG 3350) was increased in animals with early experimental pancreatitis (5.4% ± 1.2%, n = 20) when compared with control animals (1.8% ± 0.2%; n = 6) (P = 0.0005). Furthermore, intestinal macromolecular permeability to PEG 3350 correlated with severity of disease as predicted by the method of induction of pancreatitis (P = 0.0003), the histological findings (P = 0.0002), and total ascitic trypsinogen activation peptides content (P = 0.029). Conclusions: Increased gut permeability in experimental pancreatitis can be correlated with pancreatitis severity.