Effects of heparin in experimental models of acute pancreatitis and post-ERCP pancreatitis.
BACKGROUND
Acute pancreatitis (AP) is a complication of diagnostic or therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In a recent clinical trial, a decreased rate of post-ERCP pancreatitis was shown after prophylactic heparin treatment. The aim of this study was to evaluate the effects of prophylactic heparin application in various experimental models of AP and pancreatic duct obstruction and to assess the underlying mechanisms.


METHODS
In various experimental models, pancreatic injury of graded severity was induced in Wistar rats: (1) mild pancreatitis by IV cerulein infusion over 6 hours; (2) severe pancreatitis by infusion of glycodeoxycholic acid into the pancreatic duct plus IV cerulein application over 6 hours. The clinical ERCP situation was imitated in groups (3) obstruction of the pancreatic duct and (4) infusion of contrast medium into the pancreatic duct plus obstruction. In every group the animals received either no heparin (n=six per group) or continuous IV heparin (n=six per group) starting before pancreatic injury. Histologic changes, amylase, and lipase in plasma were evaluated 12 hours after induction of pancreatic injury. Additional animals were treated to investigate pancreatic microcirculation by intravital microscopy (n=six per group).


RESULTS
In groups 1, 3, and 4 (mild AP/duct obstruction/duct obstruction plus contrast medium), IV heparin-treated animals showed reduced edema, inflammation, and peak amylase values compared with the corresponding non-heparin-treated animals (P<.05). Moreover, mean erythrocyte velocity was significantly higher and leukocyte-endothelium interaction was reduced in these groups after prophylactic administration of heparin. In contrast, group 2 (severe AP) did not show any difference between control animals and animals that received heparin as assessed by histology and intravital microscopy.


CONCLUSIONS
Prophylactic systemic application of heparin provides a protective effect in mild AP and in experimental post-ERCP pancreatitis. The mechanism of the protective effects of heparin seems to be the reduction of leukocyte-endothelium interaction and the normalization of pancreatic microcirculation.
Hackert
Thilo
T
Department of Surgery and Experimental Surgery, University of Heidelberg, Heidelberg, Germany.
Werner
Jens
J
Gebhard
Martha-Maria
MM
Klar
Ernst
E
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D008853:Microscopy / Q000379:methods; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D000925:Anticoagulants; D006493:Heparin; D000681:Amylases