Skip to main content
SpringerLink
Log in

Persistent Multiple Organ Microcirculatory Disorders in Severe Acute Pancreatitis: Experimental Findings and Clinical Implications

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

This study characterizes microcirculatory changes (capillary blood flow, capillary permeability, and leukocyte rolling) in the pancreas, colon, liver, and lungs at different stages of severe acute pancreatitis (AP) in a well-established rat model using intravital microscopy and computerized image analysis. The results demonstrate that microcirculatory disorders in severe AP are not confined to the pancreas but can also be found in the colon, liver, and lungs; that they extend beyond the early stage of AP and persist for 48 hr (and longer); and that they not only affect capillary blood flow but also involve prolonged changes of capillary permeability and leukocyte endothelial interaction. These findings may explain previous observations that therapeutic strategies aimed at enhancing microcirculation improve outcome in AP even if therapy is delayed and pancreatic necrosis can no longer be influenced. Since these systemic microcirculatory disturbances may contribute to AP-associated multiple organ dysfunction syndrome, further studies are warranted to evaluate whether improvement of microcirculation stabilizes organ function in AP and how long this may be effective after disease onset.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Klar E, Schratt W, Foitzik T, Buhr H, Herfarth C, Messmer K: Impact of microcirculatory flow pattern changes on the development of acut edematous und necrotizing pancreatitis in rabbit pancreas. Dig Dis Sci 39:2639–2644, 1994

    Google Scholar 

  2. Klar E, Messmer K, Warshaw AL, Herfarth C: Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy. Br J Surg 77:1205–1210, 1990

    Google Scholar 

  3. Klar E, Foitzik T, Buhr HJ, Messmer K, Herfarth Ch: Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Ann Surg 217:369–374, 1993

    Google Scholar 

  4. Schmidt J, Huch K, Mithofer K, Hotz HG, Sinn HP, Buhr HJ, Warshaw AL, Herfarth C, Klar E: Benefits of various dextrans after delayed therapy in necrotizing pancreatitis in the rat. Intens Care Med 22:1207–213, 1996

    Google Scholar 

  5. Foitzik T, Faulhaber J, Hotz HG, Kirchengast M, Buhr HJ: Endothelin receptor blockade improves fluid sequestration, pancratic capillary blood flow, and survival in severe experimental pancreatitis. Ann Surg 228:670–675, 1998

    Google Scholar 

  6. Foitzik T, Eibl G, Hotz HG, Faulhaber J, Kirchengast M, Buhr HJ: Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates. Surgery 128:399–407, 2000

    Google Scholar 

  7. Foitzik T, Hotz HG, Eibl G, Hotz B, Kirchengast M, Buhr HJ: Therapy of microcirculatory disorders in severe acute pancreatitis: Effect of platelet-activating factor receptor blockade vs. Endothelin receptor blockade. J Gastrointest Surg 3:244–251, 1999

    Google Scholar 

  8. Gullo A, Berlot G: Ingredients of organ dysfunction or failure. World J Surg 20:430–436, 1996

    Google Scholar 

  9. Kirkpatrick CJ, Bittinger F, Klein CL, Hauptmann S, Klosterhalfen B: The role of the microcirculation in multiple organ dysfunction syndrome (MODS): A review and perspective. Virchows Arch 427:461–476, 1996

    Google Scholar 

  10. 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 215:44–56, 1992

    Google Scholar 

  11. Foitzik T, Hotz HG, Eibl G, Buhr HJ: Experimental models of acute pancreatitis. Are they suitable for evaluating therapy? J Colorectal Dis 15:127–135, 2000

    Google Scholar 

  12. Schmidt J, Fernandez del Castillo C, Rattner DW, Lewandrowski KB, Compton CC, Warshaw AL: Trypsinogen activation peptides in experimental rat Pancreatitis. Prognostic implications and and histopathologic correlates. Gastroenterology 103:1009–1016, 1992

    Google Scholar 

  13. Tenner S, Fernandes-del Castillo C, Warshaw A, Steinberg W, Hermon-Taylor J, Valenzuela JE, Hariri M, Hughes M, Banks PA: Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis. Int J Pancreatol 21:105–110, 1997

    Google Scholar 

  14. Hurley PR, Cook A, Jehanli A, Austen BM, Hermon-Taylor J: Development of radioimmunoassays for free tetra-1-aspartyl-L-lysine trypsinogen activation peptides (TAP). J Immunol Methods 111:195–203, 1988

    Google Scholar 

  15. Hotz HG, Schmidt J, Ryschich EW, Foitzik T, Buhr HJ, Warshaw AL, Herfarth C, Klar E: Isovolemic hemodilution with dextran prevents contrast medium induced impairment of pancreatic microcirculation in necrotizing pancreatitis of the rats. Am J Surg 169:161–166, 1995

    Google Scholar 

  16. Hotz HG, Foitzik T, Rohweder J, Schulzke JD, Fromm M, Runkel NSF, Buhr HJ: Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications. J Gastrointest Surg 2:518–525, 1998

    Google Scholar 

  17. Menger MD, Marzi I, Messmer K: In vivo fluorescence microscopy for quantitative analysis of the hepatic microcirculation in hamster and rats. Eur Surg Res 23:158–169, 1991

    Google Scholar 

  18. Schneider P, Foitzik T, Kahrau S, Buhr HJ: Etablierung der Intravitalmikroskopie der Lunge im Rattenmodell. Langenbecks Arch Chir 28(suppl 1):507–510, 1999

    Google Scholar 

  19. Klyscz T, Jünger M, Jung F, Zeintl H: Cap image: Ein neuartiges computer-gestütztes Videobildanalysesystem für die dynamische Kapillarmikroskopie. Biomed Technik 42:168–175, 1997

    Google Scholar 

  20. Sunamura M, Yamauchi J-1, Shibuya K, Chen H-M, Ding L, Takeda K, Kobari M, Matsuno S: Pancreatic microcirculation in acute pancreatitis. J Hepat Bil Pancreat Surg 5:62–68, 1998

    Google Scholar 

  21. Chen H-M, Hwang T-L, Chen M-F. The effect of gabexate mesilate on pancreatic and hepatic microcirculation in acute experimental pancreatitis in rats. J Surg Res 66:147–153, 1996

    Google Scholar 

  22. Uhlmann S, Uhlmann D, Spiegel H-U. Evaluation of hepatic microcirculation by in vivo microscopy. J Invest Surg 12:179–193, 1999

    Google Scholar 

  23. Kelly DM, McEntee GP, McGeeney KF, Fitzpatrick JM: Microvasculature of the pancreas, liver, and kidney in ceruleininduced pancreatitis. Arch Surg 128:293–295, 1993

    Google Scholar 

  24. Kelly DM, McEntee GP, McGeeney KF, Fitzpatrick JM: Pulmonary microvasculature in experimental acute haemorrhagic and oedematous pancreatitis. Br J Surg 78:1064–1067, 1991

    Google Scholar 

  25. Weidenbach H, Lerch MM, Gress TM, Pfaff D, Turi S, Adler G: Vasoactive mediators and the progression from edematous to necrotizing experimental acute pancreatitis. Gut 37:434–440, 1995

    Google Scholar 

  26. Yotsumoto F, Manabe T, Ohshio G, Imanishi K, Ando T, Kyogoku T, Hirano T, Tobe T: Role of pancreatic blood flow and vasoactive substances in the development of canine acute pancreatitis. J Surg Res 55:531–536, 1991

    Google Scholar 

  27. Kingsnorth A: Role of cytokines and their inhibitors in acute pancreatitis. Gut 40:1–4, 1997

    Google Scholar 

  28. Tiefenbacher W, Mann O, Schneider C, Kluth D, Izbicki JR, Bloechle C: Effekt der therapeutischen Gabe des Platelet-Activating Factor-Antagonisten WEB 2086 auf die Mikrozirkulation bei der akuten experimentellen Pankreatitis der Ratte. Langenbecks Arch Chir 29(suppl 1):563–567, 2000

    Google Scholar 

  29. Foitzik Th, Stufler M, Hotz HG, Klinnert J, Wagner J, Warshaw AL, Schulzke JD, Fromm M, Buhr HJ: Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis. J Gastrointest Surg 1:40–47, 1997

    Google Scholar 

  30. Forgacs B, Wedel E, Franke J, Eibl G, Buhr HJ, Foitzik T: Enhanced RES function in severe experimental pancreatitis following improvement of hepatic capillary blood flow. Pancreas 4:420, 1999 (abstract)

    Google Scholar 

  31. Werner J, Z'graggen K, Fernandez-del Castillo C, Lewandrowski K, Compton CC, Warshaw AL: Specific therapy for local and systemic complications of acute pancreatitis with monoclonal antibodies against ICAM-1. Ann Surg 229:834–842, 1999

    Google Scholar 

  32. Menger MD, Vollmar B, Microcirculation: initiating or aggravating factor? In: Büchler MW, Uhl W, Friess H, Malfertheiner P (eds): Acute pancreatitis: Novel concepts in biology and therapy. Berlin, Blackwell, 1999, pp 63–70

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Microcirculation and Pancreas Research Laboratory Department of Surgery, Benjamin Franklin Medical Center, Freie Universität, Berlin, Germany

    T. Foitzik, G. Eibl, B. Hotz, H. Hotz, S. Kahrau, C. Kasten, P. Schneider & H.J. Buhr

Authors
  1. T. Foitzik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Eibl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Hotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Hotz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Kahrau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Kasten
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H.J. Buhr
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Foitzik, T., Eibl, G., Hotz, B. et al. Persistent Multiple Organ Microcirculatory Disorders in Severe Acute Pancreatitis: Experimental Findings and Clinical Implications. Dig Dis Sci 47, 130–138 (2002). https://doi.org/10.1023/A:1013284008219

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1013284008219

Search

Navigation