Skip to main content
Top
Published in: Intensive Care Medicine 2/2004

01-02-2004 | Experimental

Effects of C1 esterase inhibitor administration on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia

Authors: Christian Lehmann, Jürgen Birnbaum, Carsten Lührs, Oskar Rückbeil, Claudia Spies, Sabine Ziemer, Matthias Gründling, Dragan Pavlovic, Taras Usichenko, Michael Wendt, Wolfgang J. Kox

Published in: Intensive Care Medicine | Issue 2/2004

Login to get access

Abstract

Objective

To determine the effects of C1 esterase inhibitor (C1-INH) administration on intestinal functional capillary density, leukocyte adherence, and mesenteric plasma extravasation during experimental endotoxemia.

Design and setting

Prospective, randomized, controlled animal study in the experimental laboratory of a university.

Subjects

42 male Wistar rats.

Interventions

The animals were divided into three groups. One half of the animals of each group underwent studies of intestinal functional capillary density and leukocyte adherence on venular endothelium by intravital fluorescence microscopy. In the other half of the animals mesenteric plasma extravasation (FITC albumin) was determined by intravital fluorescence microscopy. Treatment groups received endotoxin infusion of 2.5 mg/kg per hour (group 2 and 3) and 100 U/kg b.w. C1-INH (group 3) during the 2 h of endotoxemia.

Measurements and results

Endotoxemia resulted in a significant decrease in mucosal functional capillary density (18.5% vs. controls), which was reduced by C1-INH administration (9.5%). Treatment with C1-INH also significantly attenuated intestinal leukocyte adherence in submucosal venules (35% vs. endotoxin group) and mesenteric plasma extravasation (44% vs. endotoxin group).

Conclusions

C1-INH administration diminishes endotoxin-induced changes in the intestinal microcirculation during experimental endotoxemia.
Literature
2.
go back to reference Zeerleder S, Caliezi C, Redondo M, Devay J, Wuillemin WA (1999) Activation of plasma cascade systems in sepsis: role of C1 inhibitors. Schweiz Med Wochenschr 129:1410–1417PubMed Zeerleder S, Caliezi C, Redondo M, Devay J, Wuillemin WA (1999) Activation of plasma cascade systems in sepsis: role of C1 inhibitors. Schweiz Med Wochenschr 129:1410–1417PubMed
3.
go back to reference Slotman GJ, Burchard KW, Williams JJ, D’Arezzo A, Yellin SA (1986) Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension. Surgery 99:744–751PubMed Slotman GJ, Burchard KW, Williams JJ, D’Arezzo A, Yellin SA (1986) Interaction of prostaglandins, activated complement, and granulocytes in clinical sepsis and hypotension. Surgery 99:744–751PubMed
4.
go back to reference Heller A, Koch T (2000) The complement system: an old story or target of new therapeutic approaches? Anasthesiol Intensivmed Notfallmed Schmerzther 35:207–213CrossRef Heller A, Koch T (2000) The complement system: an old story or target of new therapeutic approaches? Anasthesiol Intensivmed Notfallmed Schmerzther 35:207–213CrossRef
6.
go back to reference Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple-organ-failure syndrome. Arch Surg 121:196–208CrossRef Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV (1986) Multiple-organ-failure syndrome. Arch Surg 121:196–208CrossRef
7.
go back to reference Marshall JC, Christou NV, Meakins JL (1993) The gastrointestinal tract. The “undrained abscess” of multiple organ failure. Ann Surg 218:111–119CrossRef Marshall JC, Christou NV, Meakins JL (1993) The gastrointestinal tract. The “undrained abscess” of multiple organ failure. Ann Surg 218:111–119CrossRef
8.
go back to reference Brower MS, Harpel PC (1982) Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase. J Biol Chem 257:9849–9854PubMed Brower MS, Harpel PC (1982) Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase. J Biol Chem 257:9849–9854PubMed
9.
go back to reference Hack CE, Ogilvie AC, Eisele B, Jansen PM, Wagstaff J, Thijs LG (1994) Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. Prog Clin Biol Res 388:335–357PubMed Hack CE, Ogilvie AC, Eisele B, Jansen PM, Wagstaff J, Thijs LG (1994) Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy. Prog Clin Biol Res 388:335–357PubMed
10.
go back to reference Sonntag J, Wagner MH, Liu G, Vogel M, Walka MM, Maier RF (1999) Effect of C1-inhibitor in a rat model of necrotizing enterocolitis. Biol Neonate 76:235–241CrossRef Sonntag J, Wagner MH, Liu G, Vogel M, Walka MM, Maier RF (1999) Effect of C1-inhibitor in a rat model of necrotizing enterocolitis. Biol Neonate 76:235–241CrossRef
11.
go back to reference Hack CE, Voerman HJ, Eisele B, Keinecke HO, Nuijens JH, Eerenberg AJ, Ogilvie A, Strack van Schijndel RJ, Delvos U, Thijs LG (1992) C1-esterase inhibitor substitution in sepsis. Lancet 339:378CrossRef Hack CE, Voerman HJ, Eisele B, Keinecke HO, Nuijens JH, Eerenberg AJ, Ogilvie A, Strack van Schijndel RJ, Delvos U, Thijs LG (1992) C1-esterase inhibitor substitution in sepsis. Lancet 339:378CrossRef
12.
go back to reference Caliezi C, Zeerleder S, Redondo M, Regli B, Rothen HU, Zurcher-Zenklusen R, Rieben R, Devay J, Hack CE, Lammle B, Wuillemin WA (2002) C1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction. Crit Care Med 30:1722–1728CrossRef Caliezi C, Zeerleder S, Redondo M, Regli B, Rothen HU, Zurcher-Zenklusen R, Rieben R, Devay J, Hack CE, Lammle B, Wuillemin WA (2002) C1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction. Crit Care Med 30:1722–1728CrossRef
13.
go back to reference Schmidt W, Stenzel K, Gebhard MM, Martin E, Schmidt H (1999) C1-esterase inhibitor and its effects on endotoxin-induced leukocyte adherence and plasma extravasation in postcapillary venules. Surgery 125:280–287CrossRef Schmidt W, Stenzel K, Gebhard MM, Martin E, Schmidt H (1999) C1-esterase inhibitor and its effects on endotoxin-induced leukocyte adherence and plasma extravasation in postcapillary venules. Surgery 125:280–287CrossRef
14.
go back to reference Bohlen HG, Gore RW (1976) Preparation of rat intestinal muscle and mucosa for quantitative microcirculatory studies. Microvasc Res 11:103–110CrossRef Bohlen HG, Gore RW (1976) Preparation of rat intestinal muscle and mucosa for quantitative microcirculatory studies. Microvasc Res 11:103–110CrossRef
15.
go back to reference Schmid-Schönbein GW, Zweifach BW, Kovalcheck S (1977) The application of stereological principles to morphometry of the microcirculation in different tissues. Microvasc Res 14:303–317CrossRef Schmid-Schönbein GW, Zweifach BW, Kovalcheck S (1977) The application of stereological principles to morphometry of the microcirculation in different tissues. Microvasc Res 14:303–317CrossRef
16.
go back to reference Gore RW, Bohlen HG (1977) Microvascular pressures in rat intestinal muscle and mucosal villi. Am J Physiol 233:H685–H693PubMed Gore RW, Bohlen HG (1977) Microvascular pressures in rat intestinal muscle and mucosal villi. Am J Physiol 233:H685–H693PubMed
17.
go back to reference Menger MD, Steiner D, Messmer K (1992) Microvascular ischemia-reperfusion injury in striated muscle: significance of “no reflow.” Am J Physiol 263:H1892–H1900PubMed Menger MD, Steiner D, Messmer K (1992) Microvascular ischemia-reperfusion injury in striated muscle: significance of “no reflow.” Am J Physiol 263:H1892–H1900PubMed
18.
go back to reference Jansen PM, Eisele B, de Jong IW, Chang A, Delvos U, Taylor FB Jr, Hack CE (1998) Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock. J Immunol 160:475–484PubMed Jansen PM, Eisele B, de Jong IW, Chang A, Delvos U, Taylor FB Jr, Hack CE (1998) Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock. J Immunol 160:475–484PubMed
19.
go back to reference Scherer RU, Giebler RM, Schmidt U, Paar D, Kox WJ (1996) The influence of C1-esterase inhibitor substitution on coagulation and cardiorespiratory parameters in an endotoxin-induced rabbit model of hypercoagulability. Semin Thromb Hemost 22:357–366CrossRef Scherer RU, Giebler RM, Schmidt U, Paar D, Kox WJ (1996) The influence of C1-esterase inhibitor substitution on coagulation and cardiorespiratory parameters in an endotoxin-induced rabbit model of hypercoagulability. Semin Thromb Hemost 22:357–366CrossRef
20.
go back to reference Giebler R, Schmidt U, Koch S, Peters J, Scherer R (1999) Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin. Crit Care Med 27:597–604CrossRef Giebler R, Schmidt U, Koch S, Peters J, Scherer R (1999) Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin. Crit Care Med 27:597–604CrossRef
21.
go back to reference Asghar SS, Pasch MC (2000) Therapeutic inhibition of the complement system. Y2K update. Front Biosci E63–E81 Asghar SS, Pasch MC (2000) Therapeutic inhibition of the complement system. Y2K update. Front Biosci E63–E81
22.
go back to reference Caliezi C, Wuillemin WA, Zeerleder S, Redondo M, Eisele B, Hack CE (2000) C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Pharmacol Rev 52:91–112PubMed Caliezi C, Wuillemin WA, Zeerleder S, Redondo M, Eisele B, Hack CE (2000) C1-Esterase inhibitor: an anti-inflammatory agent and its potential use in the treatment of diseases other than hereditary angioedema. Pharmacol Rev 52:91–112PubMed
23.
go back to reference Quezado ZM, Hoffman WD, Winkelstein JA, Yatsiv I, Koev CA, Cork LC, Elin RJ, Eichacker PQ, Natanson C (1994) The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure. J Exp Med 179:569–578CrossRef Quezado ZM, Hoffman WD, Winkelstein JA, Yatsiv I, Koev CA, Cork LC, Elin RJ, Eichacker PQ, Natanson C (1994) The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure. J Exp Med 179:569–578CrossRef
24.
go back to reference Stevens JH, O’Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA (1986) Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 77:1812–1816CrossRef Stevens JH, O’Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, Raffin TA (1986) Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 77:1812–1816CrossRef
25.
go back to reference Solvik UO, Haraldsen G, Fiane AE, Boretti E, Thorsby E, Mollnes TE (2001) C1-inhibitor attenuates human serum induced E-selectin expression of pig aortic endothelial cells. Transplant Proc 33:789–790CrossRef Solvik UO, Haraldsen G, Fiane AE, Boretti E, Thorsby E, Mollnes TE (2001) C1-inhibitor attenuates human serum induced E-selectin expression of pig aortic endothelial cells. Transplant Proc 33:789–790CrossRef
26.
go back to reference Lehmann TG, Heger M, Munch S, Kirschfink M, Klar E (2000) In vivo microscopy reveals that complement inhibition by C1-esterase inhibitor reduces ischemia/reperfusion injury in the liver. Transpl Int 13:S547–S550CrossRef Lehmann TG, Heger M, Munch S, Kirschfink M, Klar E (2000) In vivo microscopy reveals that complement inhibition by C1-esterase inhibitor reduces ischemia/reperfusion injury in the liver. Transpl Int 13:S547–S550CrossRef
27.
go back to reference Akita N, Nakase H, Kanemoto Y, Kaido T, Nishioka T, Sakaki (2001) The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain. No To Shinkei 53:641–644PubMed Akita N, Nakase H, Kanemoto Y, Kaido T, Nishioka T, Sakaki (2001) The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain. No To Shinkei 53:641–644PubMed
28.
go back to reference Guerrero R, Velasco F, Rodriguez M, Lopez A, Rojas R, Alvarez MA, Villalba R, Rubio V, Torres A, del Castillo D (1993) Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor. J Clin Invest 91:2754–2760CrossRef Guerrero R, Velasco F, Rodriguez M, Lopez A, Rojas R, Alvarez MA, Villalba R, Rubio V, Torres A, del Castillo D (1993) Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor. J Clin Invest 91:2754–2760CrossRef
29.
go back to reference Poulle M, Burnouf-Radosevich M, Burnouf T (1994) Large-scale preparation of highly purified human C1-inhibitor for therapeutic use. Blood Coagul Fibrinolysis 5:543–549PubMed Poulle M, Burnouf-Radosevich M, Burnouf T (1994) Large-scale preparation of highly purified human C1-inhibitor for therapeutic use. Blood Coagul Fibrinolysis 5:543–549PubMed
30.
go back to reference Horstick G, Berg O, Heimann A, Gotze O, Loos M, Hafner G, Bierbach B, Petersen S, Bhakdi S, Darius H, Horstick M, Meyer J, Kempski O (2001) Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects. Circulation 104:3125–3131CrossRef Horstick G, Berg O, Heimann A, Gotze O, Loos M, Hafner G, Bierbach B, Petersen S, Bhakdi S, Darius H, Horstick M, Meyer J, Kempski O (2001) Application of C1-esterase inhibitor during reperfusion of ischemic myocardium: dose-related beneficial versus detrimental effects. Circulation 104:3125–3131CrossRef
Metadata
Title
Effects of C1 esterase inhibitor administration on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia
Authors
Christian Lehmann
Jürgen Birnbaum
Carsten Lührs
Oskar Rückbeil
Claudia Spies
Sabine Ziemer
Matthias Gründling
Dragan Pavlovic
Taras Usichenko
Michael Wendt
Wolfgang J. Kox
Publication date
01-02-2004
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 2/2004
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-003-2042-2

Other articles of this Issue 2/2004

Intensive Care Medicine 2/2004 Go to the issue

Announcements

February 2004