Skip to main content
Log in

Platelet Function in Acute Experimental Pancreatitis

  • Published:
Journal of Gastrointestinal Surgery

Abstract

Acute pancreatitis (AP) is characterized by disturbances of pancreatic microcirculation. It remains unclear whether platelets contribute to these perfusion disturbances. The aim of our study was to investigate platelet activation and function in experimental AP. Acute pancreatitis was induced in rats: (1) control (n = 18; Ringer’s solution), (2) mild AP (n = 18; cerulein), and (3) severe AP (n = 18; glycodeoxycholic acid (GDOC) + cerulein). After 12 h, intravital microscopy was performed. Rhodamine-stained platelets were used to investigate velocity and endothelial adhesion in capillaries and venules. In addition, erythrocyte velocity and leukocyte adhesion were evaluated. Serum amylase, thromboxane A2, and histology were evaluated after 24 h in additional animals of each group. Results showed that 24 h after cerulein application, histology exhibited a mild AP, whereas GDOC induced severe necrotizing AP. Intravital microscopy showed significantly more platelet–endothelium interaction, reduced erythrocyte velocity, and increased leukocyte adherence in animals with AP compared to control animals. Thromboxane levels were significantly elevated in all AP animals and correlated with the extent of platelet activation and severity of AP. In conclusion, platelet activation plays an important role in acute, especially necrotizing, pancreatitis. Mainly temporary platelet–endothelium interaction is observed during mild AP, whereas severe AP is characterized by firm adhesion with consecutive coagulatory activation and perfusion failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Menger MD, Plusczyk T, Vollmar B. Microcirculatory derangements in acute pancreatitis. J Hepatobiliary Pancreat Surg 2001;8:187–194 (Review).

    Article  PubMed  CAS  Google Scholar 

  2. Wang XD, Wang Q, Andersson R, Ihse I. Alterations in intestinal function in acute pancreatitis in an experimental model. Br J Surg 1996;83:1537–1543.

    Article  PubMed  CAS  Google Scholar 

  3. Zhou ZG, Chen YD. Influencing factors of pancreatic microcirculatory impairment in acute pancreatitis. World J Gastroenterol 2002;8:406–412.

    PubMed  CAS  Google Scholar 

  4. Vollmar B, Menger MD. Microcirculatory dysfunction in acute pancreatitis. A new concept of pathogenesis involving vasomotion-associated arteriolar constriction and dilation. Pancreatology 2003;3:181–190.

    Article  PubMed  Google Scholar 

  5. Klar E, Herfarth C, Messmer K. Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis. Ann Surg 1990;211:346–353.

    Article  PubMed  CAS  Google Scholar 

  6. Chen HM, Shyr MH, Lau YT, Hwang TL, Chen MF. Leukocyte–endothelial adherence correlates with pancreatic nitric oxide production in early cerulein-induced pancreatitis in rats. Shock 1998;10:218–222.

    Article  PubMed  CAS  Google Scholar 

  7. Saif MW. DIC secondary to acute pancreatitis. Clin Lab Haematol 2005;27:278–282.

    Article  PubMed  CAS  Google Scholar 

  8. Agarwal N, Pitchumoni CS. Acute pancreatitis: a multisystem disease. Gastroenterologist 1993;1:115–128 (Review).

    PubMed  CAS  Google Scholar 

  9. Schmidt J, Rattner DW, Lewandrowski K, Compton CC, Mandavilli U, Knoefel WT, Warshaw AL. A better model of acute pancreatitis for evaluating therapy. Ann Surg 1992;215:44–56.

    Article  PubMed  CAS  Google Scholar 

  10. Massberg S, Enders G, Matos FC, Tomic LI, Leiderer R, Eisenmenger S, Messmer K, Krombach F. Fibrinogen deposition at the postischemic vessel wall promotes platelet adhesion during ischemia-reperfusion in vivo. Blood 1999;94:3829–3838.

    PubMed  CAS  Google Scholar 

  11. Mithofer K, Schmidt J, Gebhard MM, Buhr HJ, Herfarth C, Klar E. Measurement of blood flow in pancreatic exchange capillaries with FITC-labeled erythrocytes. Microvasc Res 1995;49:33–48.

    Article  PubMed  CAS  Google Scholar 

  12. Butcher EC, Weissman IL. Direct fluorescent labeling of cells with fluorescein or rhodamine isothiocyanate. I. Technical aspects. J Immunol Methods 1980;37:97–108.

    Article  PubMed  CAS  Google Scholar 

  13. Baatz H, Steinbauer M, Harris AG, Krombach F. Kinetics of white blood cell staining by intravascular administration of rhodamine 6G. Artif Cells Blood Substit Immobil Biotechnol 1994;22:587–592.

    Google Scholar 

  14. Bloechle C, Kusterer K, Kuehn RM, Schneider C, Knoefel WT, Izbicki JR. Inhibition of bradykinin B2 receptor preserves microcirculation in experimental pancreatitis in rats. Am J Physiol 1998;274:G42–G51.

    PubMed  CAS  Google Scholar 

  15. Hackert T, Pfeil D, Hartwig W, Gebhard MM, Buchler MW, Werner J. Platelet function in acute experimental pancreatitis induced by ischaemia-reperfusion. Br J Surg 2005;92:724–728.

    Article  PubMed  CAS  Google Scholar 

  16. Yamaguchi H, Weidenbach H, Luhrs H, Lerch MM, Dickneite G, Adler G. Combined treatment with C1 esterase inhibitor and antithrombin III improves survival in severe acute experimental pancreatitis. Gut 1997;40:531–535.

    PubMed  CAS  Google Scholar 

  17. Klar E, Foitzik T, Buhr H, Messmer K, Herfarth C. Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Clinical practicability of an experimental concept. Ann Surg 1993;217:369–374.

    Article  PubMed  CAS  Google Scholar 

  18. Shebuski RJ, Kilgore KS. Role of inflammatory mediators in thrombogenesis. J Pharmacol Exp Ther 2002;300:729–735.

    Article  PubMed  CAS  Google Scholar 

  19. Bouchard BA, Tracy PB. Platelets, leukocytes, and coagulation. Curr Opin Hematol 2001;8:263–269.

    Article  PubMed  CAS  Google Scholar 

  20. Khandoga A, Biberthaler P, Messmer K, Krombach F. Platelet–endothelial cell interactions during hepatic ischemia-reperfusion in vivo: a systematic analysis. Microvasc Res 2003;65:71–77.

    Article  PubMed  CAS  Google Scholar 

  21. Hafezi-Moghadam A, Thomas KL, Cornelssen C. A novel mouse-driven ex vivo flow chamber for the study of leukocyte and platelet function. Am J Physiol Cell Physiol 2004;286:C876–C892.

    Article  PubMed  CAS  Google Scholar 

  22. Yokoyama Y, Nimura Y, Nagino M, Bland KI, Chaudry IH. Role of thromboxane in producing hepatic injury during hepatic stress. Arch Surg 2005;140:801–807 (Review).

    Article  PubMed  CAS  Google Scholar 

  23. Yamamoto K, Ebina S, Nakanishi H, Nakahata N. Thromboxane A2 receptor-mediated signal transduction in rabbit aortic smooth muscle cells. Gen Pharmacol 1995;26:1489–1498.

    PubMed  CAS  Google Scholar 

  24. Yeo EL, Sheppard JA, Feuerstein IA. Role of P-selectin and leukocyte activation in polymorphonuclear cell adhesion to surface adherent activated platelets under physiologic shear conditions (an injury vessel wall model). Blood 1994;83:2498–2507.

    PubMed  CAS  Google Scholar 

  25. Kuijper PH, Gallardo Torres HI, Lammers JW, Sixma JJ, Koenderman L, Zwaginga JJ. Platelet and fibrin deposition at the damaged vessel wall: cooperative substrates for neutrophil adhesion under flow conditions. Blood 1997;89:166–175.

    PubMed  CAS  Google Scholar 

  26. Salter JW, Krieglstein CF, Issekutz AC, Granger DN. Platelets modulate ischemia/reperfusion-induced leukocyte recruitment in the mesenteric circulation. Am J Physiol Gastrointest Liver Physiol 2001;281:G1432–G1439.

    PubMed  CAS  Google Scholar 

  27. Ley K. Molecular mechanisms of leukocyte recruitment in the inflammatory process. Cardiovasc Res 1996;32:733–742 (Review).

    Article  PubMed  CAS  Google Scholar 

  28. Yokoyama S, Ikeda H, Haramaki N, Yasukawa H, Murohara T, Imaizumi T. Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet–leukocyte aggregates. J Am Coll Cardiol 2005;45:1280–1286.

    Article  PubMed  CAS  Google Scholar 

  29. Dole VS, Bergmeier W, Mitchell HA, Eichenberger SC, Wagner DD. Activated platelets induce Weibel–Palade body secretion and leukocyte rolling in vivo: role of P-selectin. Blood 2005;106:2334–2339.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thilo Hackert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hackert, T., Pfeil, D., Hartwig, W. et al. Platelet Function in Acute Experimental Pancreatitis. J Gastrointest Surg 11, 439–444 (2007). https://doi.org/10.1007/s11605-007-0128-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-007-0128-9

Keywords

Navigation