ET-1 induces pancreatitis-like microvascular deterioration and acinar cell injury.
Using in vivo microscopy red blood cell (RBC) velocities, functional capillary density (FCD) and capillary diameters were estimated after inducing acute pancreatitis by intraductal infusion of sodium taurocholate (0.8 ml; 4%) or after topical superfusion of the pancreas with ET-1 (100 pmol). Sodium taurocholate mediated a significant decrease in RBC velocities between 50 and 70%, transient decrease in capillary diameters by 10%, and a sustained decrease in FCD between 60 and 70% paralleled by a dramatic heterogeneity in blood flow. Topical superfusion of the exteriorized pancreas with ET-1 caused a significant decrease in RBC velocities between 65 and 75%, a sustained decrease in capillary diameters by 10%, and a decrease in FCD by 45% accompanied by an increase in flow heterogeneity. Following sodium taurocholate infusion pancreas histology revealed a severe edema and sublobular acinar cell necrosis, while topical ET-1 application displayed a severe edema of the pancreas with focal acinar cell necrosis. Thus, ET-1 mediated a deterioration of the pancreatic microcirculation, which is similar to the microcirculatory failure found in sodium taurocholate-induced experimental pancreatitis and was associated with focal acinar cell necrosis. We are thus inclined to hypothesize that endothelin released by injured endothelial cells during acute biliary pancreatitis promotes microcirculatory failure and ischemia in acute pancreatitis, eventually leading to acinar cell necrosis.
Plusczyk
T
T
Department of General Surgery, University of Saarland, Homburg/Saar, 66421, Germany.
Bersal
B
B
Westermann
S
S
Menger
M
M
Feifel
G
G
D000208:Acute Disease; D000287:Administration, Topical; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000187:drug effects; D013656:Taurocholic Acid / Q000494:pharmacology
D019332:Endothelin-1; D013656:Taurocholic Acid