Heparin inhibits protective effect of ischemic preconditioning in ischemia/reperfusion-induced acute pancreatitis

Previous studies have shown that pancreatic ischemic preconditioning or heparin, applied before induction of acute pancreatitis inhibit the development of this disease and accelerate pancreatic recovery. The aim of the study was to determine the influence of treatment with heparin on protective effect of ischemic preconditioning (IP) in ischemia/reperfusion-induced acute pancreatitis. Heparin was administered twice, before and during induction of acute pancreatitis. IP was performed by short-term clamping of celiac artery, 30 min before induction of acute pancreatitis. Acute pancreatitis was induced in rats by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed after 6-h and 24-h reperfusion.

IP applied alone caused a mild pancreatic damage associated with a limited increase in plasma amylase activity, concentration of pro-inflammatory interleukin-1β and plasma level of D-dimer. Pretreatment with heparin or IP applied alone reduced the severity of acute pancreatitis. Both these procedures caused a similar reduction in plasma lipase, amylase and interleukin-1β, as well as in histological signs of pancreatic damage. These changes were associated with partial reversion of the pancreatitis-evoked fall of pancreatic blood flow and DNA synthesis. Combination of heparin plus IP reduced the protective effect of heparin or IP applied alone. It was manifested by an increase in pancreatic damage and plasma level of lipase, amylase and interleukin-1β, as well as by reduction in pancreatic DNA synthesis and plasma concentration of D-dimer and interleukin-10.

heparin abolishes the protective effect of ischemic preconditioning in ischemia reperfusion-induced pancreatitis. This observation suggests that initial clot formation is necessary to induce pancreatic protection by IP.