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Erschienen in: European Journal of Trauma and Emergency Surgery 5/2015

01.10.2015 | Original Article

5-HT2a receptor antagonism reduces burn-induced macromolecular efflux in rats

verfasst von: J. F. Hernekamp, H. Klein, K. Schmidt, U. Kneser, T. Kremer

Erschienen in: European Journal of Trauma and Emergency Surgery | Ausgabe 5/2015

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Abstract

Background

Major thermal injuries lead to a systemic inflammatory response with systemic capillary leakage and multiple organ dysfunction. This systemic inflammatory response is induced by a variety of immunmodulative molecules including TNFα and serotonin. Unspecific serotonin antagonism leads to reduced macromolecular efflux in rat mesenteries after burn plasma transfer. The aim of the present study was to evaluate the effect of specific 5-HT2a antagonism on early burn edema.

Methods

Donor rats (DR) underwent thermal injury (100 °C water, 30 % BSA, 12 s) for positive controls. For negative controls, DR underwent sham burn (37 °C water, 30 % BSA, 12 s). DR plasma (harvested 4 h post-trauma) was transferred to healthy individuals for positive controls. Study rats received burn plasma (BP) and a Bolus injection of Ketanserin (Ket) (1 mg kg−1 body weight). Negative controls underwent sham burn plasma infusion. Intravital microscopy was performed in mesenteric venules (0/60/120 min). Edema was assessed by FITC-albumin extravasation. Additionally, leukocyte rolling and sticking (cells mm−2) as well as microhemodynamic parameters were assessed.

Results

Significant systemic capillary leakage was observed after BP transfer at 120 min and additional administration of Ket attenuated the postburn edema to sham burn levels. Ket also leads to significantly decreased leukocyte–endothelial interactions when compared to positive controls.

Conclusion

5-HT2a antagonism reduces plasma extravasation after burn plasma transfer in healthy individuals. The influence of leukocyte–endothelial interactions on postburn edema remains unclear.
Literatur
1.
5.
Zurück zum Zitat Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, et al. International union of pharmacology classification of receptors for 5-Hydroxytryptamie (Serotonin). Pharmacol Rev. 1994;46(2):157–203.PubMed Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, et al. International union of pharmacology classification of receptors for 5-Hydroxytryptamie (Serotonin). Pharmacol Rev. 1994;46(2):157–203.PubMed
8.
Zurück zum Zitat Kaumann AJ, Levy FO. 5-hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther. 2006;111(3):674–706.CrossRefPubMed Kaumann AJ, Levy FO. 5-hydroxytryptamine receptors in the human cardiovascular system. Pharmacol Ther. 2006;111(3):674–706.CrossRefPubMed
9.
Zurück zum Zitat Taheri PA, Lippton HL, Force SD, Franklin EW, Hyman AL, Lewis MF, et al. Analysis of regional hemodynamic regulation in response to scald injury. J Clin Invest. 1994;93:147–54.PubMedCentralCrossRefPubMed Taheri PA, Lippton HL, Force SD, Franklin EW, Hyman AL, Lewis MF, et al. Analysis of regional hemodynamic regulation in response to scald injury. J Clin Invest. 1994;93:147–54.PubMedCentralCrossRefPubMed
12.
Zurück zum Zitat Walther A, Peter C, Secchi A, Gebhard MM, Martin E, Schmidt H. Selective serotonin receptor antagonism and leukocyte-independent plasma extravasation during endotoxemia. Microvasc Res. 2002;63(1):135–8. doi:10.1006/mvre.2001.2370.CrossRefPubMed Walther A, Peter C, Secchi A, Gebhard MM, Martin E, Schmidt H. Selective serotonin receptor antagonism and leukocyte-independent plasma extravasation during endotoxemia. Microvasc Res. 2002;63(1):135–8. doi:10.​1006/​mvre.​2001.​2370.CrossRefPubMed
15.
16.
Zurück zum Zitat Cioffi WG, Burleson DG, Pruitt BA Jr. Leukocyte responses to injury. Arch Surg. 1993;128(11):1260–7.CrossRefPubMed Cioffi WG, Burleson DG, Pruitt BA Jr. Leukocyte responses to injury. Arch Surg. 1993;128(11):1260–7.CrossRefPubMed
17.
Zurück zum Zitat Childs EW, Udobi KF, Wood JG, Hunter FA, Smalley DM, Cheung LY. In vivo visualization of reactive oxidants and leukocyte-endothelial adherence following hemorrhagic shock. Shock. 2002;18(5):423–7.CrossRefPubMed Childs EW, Udobi KF, Wood JG, Hunter FA, Smalley DM, Cheung LY. In vivo visualization of reactive oxidants and leukocyte-endothelial adherence following hemorrhagic shock. Shock. 2002;18(5):423–7.CrossRefPubMed
18.
Zurück zum Zitat Walther A, Weihrauch M, Schmidt W, Gebhard MM, Martin E, Schmidt H. Leukocyte-independent plasma extravasation during endotoxemia. Crit Care Med. 2000;28(8):2943–8.CrossRefPubMed Walther A, Weihrauch M, Schmidt W, Gebhard MM, Martin E, Schmidt H. Leukocyte-independent plasma extravasation during endotoxemia. Crit Care Med. 2000;28(8):2943–8.CrossRefPubMed
22.
Zurück zum Zitat Yuan Y, Granger HJ, Zawieja DC, Chilian WM. Flow modulates coronary venular permeability by a nitric oxide-related mechanism. Am J Physiol Heart Circ Physiol. 1992;263:641–6. Yuan Y, Granger HJ, Zawieja DC, Chilian WM. Flow modulates coronary venular permeability by a nitric oxide-related mechanism. Am J Physiol Heart Circ Physiol. 1992;263:641–6.
25.
Zurück zum Zitat Demling RH. The burn edema process: current concepts. J Burn Care Rehabil. 2005;26(3):207–27.PubMed Demling RH. The burn edema process: current concepts. J Burn Care Rehabil. 2005;26(3):207–27.PubMed
26.
Zurück zum Zitat Ferrara JJ, Westervelt CL, Kukuy EL, Franklin EW, Choe EU, Mercurio KK, et al. Burn edema reduction by methysergide is not due to control of regional vasodilatation. J Surg Res. 1996;61:11–6.CrossRefPubMed Ferrara JJ, Westervelt CL, Kukuy EL, Franklin EW, Choe EU, Mercurio KK, et al. Burn edema reduction by methysergide is not due to control of regional vasodilatation. J Surg Res. 1996;61:11–6.CrossRefPubMed
28.
Zurück zum Zitat Vanhoutte PM, Cohen RA. The elusory role of serotonin in vascular function and disease. Biochem Pharmacol. 1983;32(24):3671–4.CrossRefPubMed Vanhoutte PM, Cohen RA. The elusory role of serotonin in vascular function and disease. Biochem Pharmacol. 1983;32(24):3671–4.CrossRefPubMed
29.
Zurück zum Zitat De Clerck F. Effects of serotonin on platelets and blood vessels. J Cardiovasc Pharmacol. 1991;17(Suppl. 5):1–5. De Clerck F. Effects of serotonin on platelets and blood vessels. J Cardiovasc Pharmacol. 1991;17(Suppl. 5):1–5.
30.
Zurück zum Zitat De Clerck F, van Gorp L, Beetens J, Reneman RS. Platelet-mediated vascular permeability in the rat: a predominant role for 5-Hydroxytryptamine. Thromb Res. 1985;38:321–39.CrossRefPubMed De Clerck F, van Gorp L, Beetens J, Reneman RS. Platelet-mediated vascular permeability in the rat: a predominant role for 5-Hydroxytryptamine. Thromb Res. 1985;38:321–39.CrossRefPubMed
31.
Zurück zum Zitat Cerrito F, Lazzaro MP, Gaudio E, Arminio P, Alois G. 5HT2-receptors and serotonin release: their role in human platetlet aggregation. Life Sci. 1993;53:209–15.CrossRefPubMed Cerrito F, Lazzaro MP, Gaudio E, Arminio P, Alois G. 5HT2-receptors and serotonin release: their role in human platetlet aggregation. Life Sci. 1993;53:209–15.CrossRefPubMed
32.
33.
36.
Zurück zum Zitat McLennan PL, Taylor DA. Antagonism by ketanserin of 5-HT-induced vasoconstriction unmasks a 5-HT-induced vasodilation. Eur J Pharmacol. 1984;104(3–4):313–8.CrossRefPubMed McLennan PL, Taylor DA. Antagonism by ketanserin of 5-HT-induced vasoconstriction unmasks a 5-HT-induced vasodilation. Eur J Pharmacol. 1984;104(3–4):313–8.CrossRefPubMed
37.
Zurück zum Zitat Bertoni S, Ghizzardi P, Cattaruzza F, Ballabeni V, Impicciatore M, Tognolini M, et al. Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice. Pharmacol Res. 2007;56(6):550–5. doi:10.1016/j.phrs.2007.10.004.CrossRefPubMed Bertoni S, Ghizzardi P, Cattaruzza F, Ballabeni V, Impicciatore M, Tognolini M, et al. Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice. Pharmacol Res. 2007;56(6):550–5. doi:10.​1016/​j.​phrs.​2007.​10.​004.CrossRefPubMed
38.
Zurück zum Zitat Holliman CJ, Meuleman TR, Larsen KR, Port JD, Stanley TH, Pace NL, et al. The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model. J Trauma. 1983;23(10):867–71.CrossRefPubMed Holliman CJ, Meuleman TR, Larsen KR, Port JD, Stanley TH, Pace NL, et al. The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model. J Trauma. 1983;23(10):867–71.CrossRefPubMed
39.
Zurück zum Zitat Ogawa T, Sugidachi A, Tanaka N, Fujimoto K, Asai F. Pharmacological profiles of R-96544, the active form of a novel 5-HT2A receptor antagonist R-102444. Eur J Pharmacol. 2002;457(2–3):107–14.CrossRefPubMed Ogawa T, Sugidachi A, Tanaka N, Fujimoto K, Asai F. Pharmacological profiles of R-96544, the active form of a novel 5-HT2A receptor antagonist R-102444. Eur J Pharmacol. 2002;457(2–3):107–14.CrossRefPubMed
40.
Zurück zum Zitat Barbe F, Gautier E, Bidouard JP, Grosset A, O’Connor SE, Janiak P. SL65.0472 blocks 5-hydroxytryptamine-induced vasoconstriction in a dog hindlimb ischemia model. Eur J Pharmacol. 2003;474(1):117–20.CrossRefPubMed Barbe F, Gautier E, Bidouard JP, Grosset A, O’Connor SE, Janiak P. SL65.0472 blocks 5-hydroxytryptamine-induced vasoconstriction in a dog hindlimb ischemia model. Eur J Pharmacol. 2003;474(1):117–20.CrossRefPubMed
41.
Zurück zum Zitat Dhennin C, Vesin L, Feauveaux JF. Ketanserin as an adjunct to burn treatment. Intensive Care Med. 1988;14(6):677–8.CrossRefPubMed Dhennin C, Vesin L, Feauveaux JF. Ketanserin as an adjunct to burn treatment. Intensive Care Med. 1988;14(6):677–8.CrossRefPubMed
42.
Zurück zum Zitat Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, et al. Ketanserin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 2000;(2). doi:10.1002/14651858.CD000954. Pope J, Fenlon D, Thompson A, Shea B, Furst D, Wells G, et al. Ketanserin for Raynaud’s phenomenon in progressive systemic sclerosis. Cochrane Database Syst Rev. 2000;(2). doi:10.​1002/​14651858.​CD000954.
Metadaten
Titel
5-HT2a receptor antagonism reduces burn-induced macromolecular efflux in rats
verfasst von
J. F. Hernekamp
H. Klein
K. Schmidt
U. Kneser
T. Kremer
Publikationsdatum
01.10.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Trauma and Emergency Surgery / Ausgabe 5/2015
Print ISSN: 1863-9933
Elektronische ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-014-0486-4

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