Skip to main content
Erschienen in: Inflammation 6/2013

01.12.2013

Sivelestat Prevents Cytoskeletal Rearrangements in Neutrophils Resulting from Lung Re-expansion Following One-Lung Ventilation During Thoracic Surgery

verfasst von: Takashi Eguchi, Kazuo Yoshida, Ryoichi Kondo, Kazutoshi Hamanaka, Takayuki Shiina, Yoshimichi Komatsu, Hiroshi Yamamoto, Keishi Kubo, Jo Hasegawa, Tomonobu Koizumi

Erschienen in: Inflammation | Ausgabe 6/2013

Einloggen, um Zugang zu erhalten

Abstract

Patients undergoing lobectomy are at risk of developing acute lung injury resulting from one-lung ventilation (OLV) during surgery. We investigated the morphological and functional behavior of neutrophils in patients who underwent lobectomy and assessed the ability of sivelestat to inhibit neutrophil activity. This was a blinded randomized study. Sixteen patients who underwent lobectomy were given intravenous sivelestat (n = 8) or intravenous saline (n = 8). We studied the cytoskeletal rearrangements of circulating neutrophils by determining the localization of filamentous actin (F-actin). Pulmonary oxygenation was evaluated by measuring the partial pressure of arterial oxygen. We found that the number of circulating, F-actin-rimmed neutrophils increased during OLV and after lung re-expansion. Our results suggest that, in addition to the surgical procedure and OLV, re-expansion of the remaining lung after lobectomy increases the neutrophil activation levels. Furthermore, administration of sivelestat limited neutrophil activation and improved pulmonary oxygenation in our patients.
Literatur
2.
Zurück zum Zitat Pittet, J.F., R.C. Mackersie, T.R. Martin, and M.A. Matthay. 1997. Biological markers of acute lung injury: Prognostic and pathogenetic significance. Am J Respir Crit Care Med 155: 1187–1205.PubMedCrossRef Pittet, J.F., R.C. Mackersie, T.R. Martin, and M.A. Matthay. 1997. Biological markers of acute lung injury: Prognostic and pathogenetic significance. Am J Respir Crit Care Med 155: 1187–1205.PubMedCrossRef
3.
Zurück zum Zitat Kozian, A., T. Schilling, F. Freden, E. Maripuu, C. Rocken, C. Strang, T. Hachenberg, and G. Hedenstierna. 2008. One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: An experimental study. Br J Anaesth 100: 549–559.PubMedCrossRef Kozian, A., T. Schilling, F. Freden, E. Maripuu, C. Rocken, C. Strang, T. Hachenberg, and G. Hedenstierna. 2008. One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung: An experimental study. Br J Anaesth 100: 549–559.PubMedCrossRef
4.
Zurück zum Zitat Doerschuk, C.M. 2001. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8: 71–88.PubMed Doerschuk, C.M. 2001. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 8: 71–88.PubMed
5.
Zurück zum Zitat Drost, E.M., and W. MacNee. 2002. Potential role of IL-8, platelet-activating factor and TNF-alpha in the sequestration of neutrophils in the lung: Effects on neutrophil deformability, adhesion receptor expression, and chemotaxis. Eur J Immunol 32: 393–403.PubMedCrossRef Drost, E.M., and W. MacNee. 2002. Potential role of IL-8, platelet-activating factor and TNF-alpha in the sequestration of neutrophils in the lung: Effects on neutrophil deformability, adhesion receptor expression, and chemotaxis. Eur J Immunol 32: 393–403.PubMedCrossRef
6.
Zurück zum Zitat Komatsu, Y., H. Yamamoto, K. Tsushima, S. Furuya, S. Yoshikawa, M. Yasuo, K. Kubo, Y. Yamazaki, J. Hasegawa, T. Eguchi, R. Kondo, K. Yoshida, and T. Koizumi. 2012. Increased interleukin-8 in epithelial lining fluid of collapsed lungs during one-lung ventilation for thoracotomy. Inflammation 35: 1844–1850.PubMedCrossRef Komatsu, Y., H. Yamamoto, K. Tsushima, S. Furuya, S. Yoshikawa, M. Yasuo, K. Kubo, Y. Yamazaki, J. Hasegawa, T. Eguchi, R. Kondo, K. Yoshida, and T. Koizumi. 2012. Increased interleukin-8 in epithelial lining fluid of collapsed lungs during one-lung ventilation for thoracotomy. Inflammation 35: 1844–1850.PubMedCrossRef
7.
Zurück zum Zitat Lee, C.T., A.M. Fein, M. Lippmann, H. Holtzman, P. Kimbel, and G. Weinbaum. 1981. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med 304: 192–196.PubMedCrossRef Lee, C.T., A.M. Fein, M. Lippmann, H. Holtzman, P. Kimbel, and G. Weinbaum. 1981. Elastolytic activity in pulmonary lavage fluid from patients with adult respiratory-distress syndrome. N Engl J Med 304: 192–196.PubMedCrossRef
8.
Zurück zum Zitat Ryugo, M., Y. Sawa, H. Takano, G. Matsumiya, S. Iwai, M. Ono, H. Hata, T. Yamauchi, M. Nishimura, Y. Fujino, and H. Matsuda. 2006. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: Findings of a double-blind randomized study. Surg Today 36: 321–326.PubMedCrossRef Ryugo, M., Y. Sawa, H. Takano, G. Matsumiya, S. Iwai, M. Ono, H. Hata, T. Yamauchi, M. Nishimura, Y. Fujino, and H. Matsuda. 2006. Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: Findings of a double-blind randomized study. Surg Today 36: 321–326.PubMedCrossRef
9.
Zurück zum Zitat Tamakuma, S., M. Ogawa, N. Aikawa, T. Kubota, H. Hirasawa, A. Ishizaka, N. Taenaka, C. Hamada, S. Matsuoka, and T. Abiru. 2004. Relationship between neutrophil elastase and acute lung injury in humans. Pulm Pharmacol Ther 17: 271–279.PubMedCrossRef Tamakuma, S., M. Ogawa, N. Aikawa, T. Kubota, H. Hirasawa, A. Ishizaka, N. Taenaka, C. Hamada, S. Matsuoka, and T. Abiru. 2004. Relationship between neutrophil elastase and acute lung injury in humans. Pulm Pharmacol Ther 17: 271–279.PubMedCrossRef
10.
Zurück zum Zitat Inoue, Y., H. Tanaka, H. Ogura, I. Ukai, K. Fujita, H. Hosotsubo, T. Shimazu, and H. Sugimoto. 2006. A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury. J Trauma 60: 936–943. discussion 943.PubMedCrossRef Inoue, Y., H. Tanaka, H. Ogura, I. Ukai, K. Fujita, H. Hosotsubo, T. Shimazu, and H. Sugimoto. 2006. A neutrophil elastase inhibitor, sivelestat, improves leukocyte deformability in patients with acute lung injury. J Trauma 60: 936–943. discussion 943.PubMedCrossRef
11.
Zurück zum Zitat Matsuzaki, K., Y. Hiramatsu, S. Homma, S. Sato, O. Shigeta, and Y. Sakakibara. 2005. Sivelestat reduces inflammatory mediators and preserves neutrophil deformability during simulated extracorporeal circulation. Ann Thorac Surg 80: 611–617.PubMedCrossRef Matsuzaki, K., Y. Hiramatsu, S. Homma, S. Sato, O. Shigeta, and Y. Sakakibara. 2005. Sivelestat reduces inflammatory mediators and preserves neutrophil deformability during simulated extracorporeal circulation. Ann Thorac Surg 80: 611–617.PubMedCrossRef
12.
Zurück zum Zitat Saito, H., J. Lai, R. Rogers, and C.M. Doerschuk. 2002. Mechanical properties of rat bone marrow and circulating neutrophils and their responses to inflammatory mediators. Blood 99: 2207–2213.PubMedCrossRef Saito, H., J. Lai, R. Rogers, and C.M. Doerschuk. 2002. Mechanical properties of rat bone marrow and circulating neutrophils and their responses to inflammatory mediators. Blood 99: 2207–2213.PubMedCrossRef
13.
Zurück zum Zitat Yoshida, K., R. Kondo, Q. Wang, and C.M. Doerschuk. 2006. Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats. Am J Respir Crit Care Med 174: 689–698.PubMedCrossRef Yoshida, K., R. Kondo, Q. Wang, and C.M. Doerschuk. 2006. Neutrophil cytoskeletal rearrangements during capillary sequestration in bacterial pneumonia in rats. Am J Respir Crit Care Med 174: 689–698.PubMedCrossRef
14.
Zurück zum Zitat Kaynar, A.M., A.M. Houghton, E.H. Lum, B.R. Pitt, and S.D. Shapiro. 2008. Neutrophil elastase is needed for neutrophil emigration into lungs in ventilator-induced lung injury. Am J Respir Cell Mol Biol 39: 53–60.PubMedCrossRef Kaynar, A.M., A.M. Houghton, E.H. Lum, B.R. Pitt, and S.D. Shapiro. 2008. Neutrophil elastase is needed for neutrophil emigration into lungs in ventilator-induced lung injury. Am J Respir Cell Mol Biol 39: 53–60.PubMedCrossRef
15.
Zurück zum Zitat Cai, T.Q., and S.D. Wright. 1996. Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte adhesion. J Exp Med 184: 1213–1223.PubMedCrossRef Cai, T.Q., and S.D. Wright. 1996. Human leukocyte elastase is an endogenous ligand for the integrin CR3 (CD11b/CD18, Mac-1, alpha M beta 2) and modulates polymorphonuclear leukocyte adhesion. J Exp Med 184: 1213–1223.PubMedCrossRef
16.
Zurück zum Zitat Kuebler, W.M., G.E. Kuhnle, J. Groh, and A.E. Goetz. 1994. Leukocyte kinetics in pulmonary microcirculation: Intravital fluorescence microscopic study. J Appl Physiol 76: 65–71.PubMed Kuebler, W.M., G.E. Kuhnle, J. Groh, and A.E. Goetz. 1994. Leukocyte kinetics in pulmonary microcirculation: Intravital fluorescence microscopic study. J Appl Physiol 76: 65–71.PubMed
17.
Zurück zum Zitat Tanaka, H., M. Nishino, and T.E. Dahms. 2002. Physiologic responses to small emboli and hemodynamic effects of changes in deformability of polymorphonuclear leukocytes in isolated rabbit lung. Microvasc Res 63: 81–90.PubMedCrossRef Tanaka, H., M. Nishino, and T.E. Dahms. 2002. Physiologic responses to small emboli and hemodynamic effects of changes in deformability of polymorphonuclear leukocytes in isolated rabbit lung. Microvasc Res 63: 81–90.PubMedCrossRef
18.
Zurück zum Zitat Inoue, Y., A. Seiyama, H. Tanaka, I. Ukai, P. Akimau, M. Nishino, T. Shimazu, and H. Sugimoto. 2005. Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation. Crit Care Med 33: 1814–1822.PubMedCrossRef Inoue, Y., A. Seiyama, H. Tanaka, I. Ukai, P. Akimau, M. Nishino, T. Shimazu, and H. Sugimoto. 2005. Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation. Crit Care Med 33: 1814–1822.PubMedCrossRef
19.
Zurück zum Zitat Hofman, P., L. d'Andrea, E. Guzman, E. Selva, G. Le Negrate, D.F. Far, E. Lemichez, P. Boquet, and B. Rossi. 1999. Neutrophil F-actin and myosin but not microtubules functionally regulate transepithelial migration induced by interleukin 8 across a cultured intestinal epithelial monolayer. Eur Cytokine Netw 10: 227–236.PubMed Hofman, P., L. d'Andrea, E. Guzman, E. Selva, G. Le Negrate, D.F. Far, E. Lemichez, P. Boquet, and B. Rossi. 1999. Neutrophil F-actin and myosin but not microtubules functionally regulate transepithelial migration induced by interleukin 8 across a cultured intestinal epithelial monolayer. Eur Cytokine Netw 10: 227–236.PubMed
20.
Zurück zum Zitat de Perrot, M., M. Liu, T.K. Waddell, and S. Keshavjee. 2003. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 167: 490–511.PubMedCrossRef de Perrot, M., M. Liu, T.K. Waddell, and S. Keshavjee. 2003. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med 167: 490–511.PubMedCrossRef
21.
Zurück zum Zitat Misthos, P., S. Katsaragakis, N. Milingos, S. Kakaris, E. Sepsas, K. Athanassiadi, D. Theodorou, and I. Skottis. 2005. Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation. Eur J Cardiothorac Surg 27: 379–382. discussion 382-373.PubMedCrossRef Misthos, P., S. Katsaragakis, N. Milingos, S. Kakaris, E. Sepsas, K. Athanassiadi, D. Theodorou, and I. Skottis. 2005. Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation. Eur J Cardiothorac Surg 27: 379–382. discussion 382-373.PubMedCrossRef
22.
Zurück zum Zitat Beatty, K., J. Bieth, and J. Travis. 1980. Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. J Biol Chem 255: 3931–3934.PubMed Beatty, K., J. Bieth, and J. Travis. 1980. Kinetics of association of serine proteinases with native and oxidized alpha-1-proteinase inhibitor and alpha-1-antichymotrypsin. J Biol Chem 255: 3931–3934.PubMed
Metadaten
Titel
Sivelestat Prevents Cytoskeletal Rearrangements in Neutrophils Resulting from Lung Re-expansion Following One-Lung Ventilation During Thoracic Surgery
verfasst von
Takashi Eguchi
Kazuo Yoshida
Ryoichi Kondo
Kazutoshi Hamanaka
Takayuki Shiina
Yoshimichi Komatsu
Hiroshi Yamamoto
Keishi Kubo
Jo Hasegawa
Tomonobu Koizumi
Publikationsdatum
01.12.2013
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 6/2013
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-013-9689-9

Weitere Artikel der Ausgabe 6/2013

Inflammation 6/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.