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Erschienen in: European Journal of Plastic Surgery 3/2013

01.03.2013 | Experimental Study

Effects of neutrophil elastase inhibitor on flap survival after venous ischemia

verfasst von: Kunio Kotsu, Ichiro Hashimoto, Masahiro Yamano, Keisuke Kashiwagi, Yoshiro Abe, Hideki Nakanishi

Erschienen in: European Journal of Plastic Surgery | Ausgabe 3/2013

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Abstract

Background

Venous ischemia is more of a threat to tissue viability than is arterial ischemia. The mechanism of injury is complex and involves many factors. Neutrophil activation is thought to be a trigger and final pathway for the tissue injury.

Methods

We conducted a two-part animal study to examine the effect of neutrophil elastase inhibitor on ischemia–reperfusion injury. In the first experiment, island abdominal skin flaps were elevated in 20 rabbits (ten treated with neutrophil elastase inhibitor and ten not treated), and the pedicle vein was occluded for 6 h in both groups. Survival rates (i.e., flap survival areas) and histologic findings were compared. In the second experiment, thrombus formation was assessed in arterioles and venules injured by reactive oxygen species.

Results

Survival of the treated flaps and non-treated flaps was 91 (46–100) and 0 (0–98) %, respectively, and differed significantly (p < 0.002). Histologically, infiltration of neutrophils was observed 12 h after congestion, and severe obstruction of vessels due to thrombi was observed 48 h after congestion in the non-treatment group, but vessels were not obstructed in the treated group. Thrombi in venules contained leukocytes, but those in arterioles did not. Time to stasis in the venules in the treatment group and non-treatment group was 130.5 (96–197) and 93 (62–133) s, respectively (p < 0.01).

Conclusions

Neutrophil elastase inhibitor was shown to maintain flap circulation and thus promote flap survival. This agent may slow thrombus formation in venules by acting on neutrophils in the venules.
Literatur
1.
Zurück zum Zitat Kerrigan CL, Wizman P, Hjortdal VE, Sampalis J (1994) Global flap ischemia: a comparison of arterial versus venous etiology. Plast Reconstr Surg 93:1485–1495PubMedCrossRef Kerrigan CL, Wizman P, Hjortdal VE, Sampalis J (1994) Global flap ischemia: a comparison of arterial versus venous etiology. Plast Reconstr Surg 93:1485–1495PubMedCrossRef
2.
Zurück zum Zitat Siemionow M, Arslan E (2004) Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery 24:468–475PubMedCrossRef Siemionow M, Arslan E (2004) Ischemia/reperfusion injury: a review in relation to free tissue transfers. Microsurgery 24:468–475PubMedCrossRef
3.
Zurück zum Zitat Hauge EM, Balling E, Hartmund T, Hjortdal VE (1997) Secondary ischemia caused by venous or arterial occlusion shows differential effects on myocutaneous island flap survival and muscle ATP levels. Plast Reconstr Surg 99:825–833PubMedCrossRef Hauge EM, Balling E, Hartmund T, Hjortdal VE (1997) Secondary ischemia caused by venous or arterial occlusion shows differential effects on myocutaneous island flap survival and muscle ATP levels. Plast Reconstr Surg 99:825–833PubMedCrossRef
4.
Zurück zum Zitat Marzella L, Jesudass RR, Manson PN, Myers RA, Bulkley GB (1988) Functional and structural evaluation of the vasculature of skin flaps after ischemia and reperfusion. Plast Reconstr Surg 81:742–750PubMedCrossRef Marzella L, Jesudass RR, Manson PN, Myers RA, Bulkley GB (1988) Functional and structural evaluation of the vasculature of skin flaps after ischemia and reperfusion. Plast Reconstr Surg 81:742–750PubMedCrossRef
5.
Zurück zum Zitat Messsina LM (1990) In vivo assessment of acute microvascullar injury after reperfusion of ischemic tibialis anterior muscle of the hamster. J Surg Res 48:615–621CrossRef Messsina LM (1990) In vivo assessment of acute microvascullar injury after reperfusion of ischemic tibialis anterior muscle of the hamster. J Surg Res 48:615–621CrossRef
6.
Zurück zum Zitat Zamboni WA, Roth AC, Russell RC, Graham B, Suchy H, Kucan JO (1993) Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. Plast Reconstr Surg 91:1110–1123PubMedCrossRef Zamboni WA, Roth AC, Russell RC, Graham B, Suchy H, Kucan JO (1993) Morphologic analysis of the microcirculation during reperfusion of ischemic skeletal muscle and the effect of hyperbaric oxygen. Plast Reconstr Surg 91:1110–1123PubMedCrossRef
7.
Zurück zum Zitat Hashimoto I, Nakanishi H, Shono Y, Yamano M, Toda M (2003) The features of thrombus in a microvessel injury model and the antithrombotic efficacy of heparin, urokinase, and prostaglandin E1. Plast Reconstr Surg 111:2307–2314PubMedCrossRef Hashimoto I, Nakanishi H, Shono Y, Yamano M, Toda M (2003) The features of thrombus in a microvessel injury model and the antithrombotic efficacy of heparin, urokinase, and prostaglandin E1. Plast Reconstr Surg 111:2307–2314PubMedCrossRef
8.
Zurück zum Zitat Hashimoto I, Nakanishi H, Shono Y, Tanaka S (1999) The effects of desferrioxamine on thrombus formation in injured microvessels of the rabbit ear. J Med Invest 46:200–204PubMed Hashimoto I, Nakanishi H, Shono Y, Tanaka S (1999) The effects of desferrioxamine on thrombus formation in injured microvessels of the rabbit ear. J Med Invest 46:200–204PubMed
9.
Zurück zum Zitat Khalil AA, Aziz FA, Hall JC (2006) Reperfusion injury. Plast Reconstr Surg 2006:1024–1033 Khalil AA, Aziz FA, Hall JC (2006) Reperfusion injury. Plast Reconstr Surg 2006:1024–1033
10.
Zurück zum Zitat Faxon DP, Gibbons RJ, Chronos NA, Gurbel PA, Sheehan F, Investigators HALT-MI (2002) The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study. J Am Coll Cardiol 40:1199–1204PubMedCrossRef Faxon DP, Gibbons RJ, Chronos NA, Gurbel PA, Sheehan F, Investigators HALT-MI (2002) The effect of blockade of the CD11/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: the results of the HALT-MI study. J Am Coll Cardiol 40:1199–1204PubMedCrossRef
11.
Zurück zum Zitat May JW Jr, Chait LA, O'Brien BM, Hurley JV (1978) The no-reflow phenomenon in experimental free flaps. Plast Reconstr Surg 61:256–267PubMedCrossRef May JW Jr, Chait LA, O'Brien BM, Hurley JV (1978) The no-reflow phenomenon in experimental free flaps. Plast Reconstr Surg 61:256–267PubMedCrossRef
12.
Zurück zum Zitat Gould JS, Sully L, O'Brien BM, Das SK, Knight KR, Hurley JV (1985) The effects of combined cooling and perfusion on experimental free-flap survival in rabbits. Plast Reconstr Surg 76:104–109PubMedCrossRef Gould JS, Sully L, O'Brien BM, Das SK, Knight KR, Hurley JV (1985) The effects of combined cooling and perfusion on experimental free-flap survival in rabbits. Plast Reconstr Surg 76:104–109PubMedCrossRef
13.
Zurück zum Zitat van den Heuvel MG, Buurman WA, Bast A, van der Hulst RR (2009) Review: ischemia–reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg 62:721–726PubMedCrossRef van den Heuvel MG, Buurman WA, Bast A, van der Hulst RR (2009) Review: ischemia–reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg 62:721–726PubMedCrossRef
14.
Zurück zum Zitat Kerrigan CL, Stotland MA (1993) Ischemia–reperfusion injury: a review. Microsurgery 14:165–175PubMedCrossRef Kerrigan CL, Stotland MA (1993) Ischemia–reperfusion injury: a review. Microsurgery 14:165–175PubMedCrossRef
15.
Zurück zum Zitat Weiss SJ, Curnutte JT, Regiani S (1986) Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. J Immunol 136:636–641PubMed Weiss SJ, Curnutte JT, Regiani S (1986) Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes. J Immunol 136:636–641PubMed
16.
Zurück zum Zitat Ishikawa N, Oda M, Kawaguchi M, Tsunezuka Y, Watanabe G (2003) The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia–reperfusion injury. Transpl Int 16:341–346PubMedCrossRef Ishikawa N, Oda M, Kawaguchi M, Tsunezuka Y, Watanabe G (2003) The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia–reperfusion injury. Transpl Int 16:341–346PubMedCrossRef
17.
Zurück zum Zitat Kambe M, Bessho R, Fujii M, Ochi M, Shimizu K (2009) Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. Interact Cardiovasc Thorac Surg 8:629–634PubMedCrossRef Kambe M, Bessho R, Fujii M, Ochi M, Shimizu K (2009) Sivelestat reduces myocardial ischemia and reperfusion injury in rat hearts even when administered after onset of myocardial ischemia. Interact Cardiovasc Thorac Surg 8:629–634PubMedCrossRef
18.
Zurück zum Zitat Uchida Y, Freitas MC, Zhao D, Busuttil RW, Kupiec-Weglinski JW (2010) The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury. Transplantation 89:1050–1056PubMedCrossRef Uchida Y, Freitas MC, Zhao D, Busuttil RW, Kupiec-Weglinski JW (2010) The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury. Transplantation 89:1050–1056PubMedCrossRef
19.
Zurück zum Zitat Hayama T, Matsuyama M, Funao K, Tanaka T, Tsuchida K, Takemoto Y, Kawahito Y, Sano H, Nakatani T, Yoshimura R (2006) Beneficial effect of neutrophil elastase inhibitor on renal warm ischemia–reperfusion injury in the rat. Transplant Proc 38:2201–2202PubMedCrossRef Hayama T, Matsuyama M, Funao K, Tanaka T, Tsuchida K, Takemoto Y, Kawahito Y, Sano H, Nakatani T, Yoshimura R (2006) Beneficial effect of neutrophil elastase inhibitor on renal warm ischemia–reperfusion injury in the rat. Transplant Proc 38:2201–2202PubMedCrossRef
20.
Zurück zum Zitat Akiyama D, Hara T, Yoshitomi O, Maekawa T, Cho S, Sumikawa K (2010) Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine. J Anesth 24:575–581PubMedCrossRef Akiyama D, Hara T, Yoshitomi O, Maekawa T, Cho S, Sumikawa K (2010) Postischemic infusion of sivelestat sodium hydrate, a selective neutrophil elastase inhibitor, protects against myocardial stunning in swine. J Anesth 24:575–581PubMedCrossRef
21.
Zurück zum Zitat Kusner DJ, King CH (1989) Protease-modulation of neutrophil superoxide response. J Immunol 143:1696–1702PubMed Kusner DJ, King CH (1989) Protease-modulation of neutrophil superoxide response. J Immunol 143:1696–1702PubMed
22.
Zurück zum Zitat Yamaguchi Y, Matsumura F, Wang FS, Akizuki E, Liang J, Matsuda T, Okabe K, Ohshiro H, Horiuchi T, Yamada S, Mori K, Ogawa M (1998) Neutrophil elastase enhances intercellular adhesion molecule-1 expression. Transplantation 65:1622–1628PubMedCrossRef Yamaguchi Y, Matsumura F, Wang FS, Akizuki E, Liang J, Matsuda T, Okabe K, Ohshiro H, Horiuchi T, Yamada S, Mori K, Ogawa M (1998) Neutrophil elastase enhances intercellular adhesion molecule-1 expression. Transplantation 65:1622–1628PubMedCrossRef
23.
Zurück zum Zitat Demirseren ME, Sarici M, Gokrem S, Yenidunya S (2007) Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in venous ischemia–reperfusion injury: experimental study in rats. J Reconstr Microsurg 23:41–44PubMedCrossRef Demirseren ME, Sarici M, Gokrem S, Yenidunya S (2007) Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in venous ischemia–reperfusion injury: experimental study in rats. J Reconstr Microsurg 23:41–44PubMedCrossRef
24.
Zurück zum Zitat Tosa Y, Lee WP, Kollias N, Randolph MA, May JW Jr (1998) Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps against ischemia–reperfusion injury: an experimental study in rats. Plast Reconstr Surg 101:1586–1594PubMedCrossRef Tosa Y, Lee WP, Kollias N, Randolph MA, May JW Jr (1998) Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps against ischemia–reperfusion injury: an experimental study in rats. Plast Reconstr Surg 101:1586–1594PubMedCrossRef
Metadaten
Titel
Effects of neutrophil elastase inhibitor on flap survival after venous ischemia
verfasst von
Kunio Kotsu
Ichiro Hashimoto
Masahiro Yamano
Keisuke Kashiwagi
Yoshiro Abe
Hideki Nakanishi
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
European Journal of Plastic Surgery / Ausgabe 3/2013
Print ISSN: 0930-343X
Elektronische ISSN: 1435-0130
DOI
https://doi.org/10.1007/s00238-012-0804-1

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