Pathophysiological role of platelets in acute experimental pancreatitis: influence of endothelin A receptor blockade.
The potential pathophysiological role of platelet-endothelium interactions was investigated during ischemia/reperfusion (I/R), and the effect of a selective endothelin(A) receptor antagonist (ET(A)-RA) was evaluated in an acute pancreatitis model. Acute pancreatitis was induced by warm ischemia (60 min) in Wistar rats, and its effects with and without antagonist treatment were investigated. Equivalent sham-operated animals were also studied. Microcirculatory changes were assessed by in vivo microscopy, and serum levels for lipase/amylase and histological specimens were investigated. Capillary constriction to 83.7 +/- 6.7% of sham-operated diameters was observed after 60 min of ischemia. A capillary density of 56.8 +/- 9.3% of the sham-operated group (396.3 +/- 15.8 mm(-1)) was measured after reperfusion. Stagnant leukocytes (329.5 +/- 30.4%) and platelets (337.5 +/- 32.3%) increased in postcapillary venules (P < 0.05). Administration of the ET(A)-RA significantly reduced I/R injury. Capillary diameters were maintained (101.4 +/- 4.5%), and capillary density was improved to 73.3 +/- 7.6% of sham-operated animals (P < 0.05). Stagnant leukocytes (152.3 +/- 10.6%) and platelets (207.1 +/- 19.8%) in sinusoids and postcapillary venules were reduced (P < 0.05). The extent of acute pancreatitis was reduced in the therapy group as indicated by serum lipase/amylase values and histological tissue damage (P < 0.05). Thus, ET(A)-RA therapy was effective in reducing I/R-induced pancreatitis in this experimental model.
Uhlmann
Dirk
D
2nd Department of Surgery, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany. Uhld@medizin.uni-leipzig.de
Lauer
Heike
H
Serr
Frederik
F
Ludwig
Stefan
S
Tannapfel
Andrea
A
Fiedler
Martin
M
Hauss
Johann
J
Witzigmann
Helmut
H
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D005260:Female; D008049:Lipase / Q000097:blood; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010179:Pancreas / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D010666:Phenylpropionates / Q000494:pharmacology; D010973:Platelet Adhesiveness; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology
D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D044022:Receptor, Endothelin A; D008049:Lipase; D000681:Amylases; C467894:ambrisentan