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Karotis-Endarterektomie in der Ratte

Ein Beispiel gefäßchirurgischer Grundlagenforschung

Carotid endarterectomy in the rat model

An example of basic research in vascular surgery

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Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Eine durch Hyperplasie der Neointima verursachte Restenose schränkt die Langzeitergebnisse chirurgischer Gefäßrekonstruktionen ein. Studien berichteten über eine reduzierte Aktivität der zyklischen Guanosinmonophosphat-Signaltransduktion im Rahmen der Neointimabildung. Im Rattenmodell der Endarterektomie haben wir die Effekte des selektiven Phosphodiesterase-5-Inhibitors Vardenafil untersucht, dessen Wirkung auf einer Hemmung des zyklisches Guanosinmonophosphat-Abbaus beruht. Es wurde eine Arteriotomie mit Endothelentfernung an der rechten A. carotis communis männlicher Ratten durchgeführt. Die Versuchsgruppen bestanden aus neun Kontrolltieren und neun Vardenafil-behandelten Tieren (10 mg/kg/Tag). Nach drei Wochen wurden die Gefäßwandschichten an mit Hematoxylin und Eosin gefärbten mikroskopischen Bildern begutachtet. Bei der immunohistochemischen Analyse zeigte sich intensive Transforming-growth-factor-beta1- und -alpha-smooth-muscle-Actin-Immunreaktivität in der Neointima der zur Kontrolle endarterektomierten Ratten. Die Behandlung mit Vardenafil führte zur Reduktion der Stenose (24,64±7,46% vs. 54,12±10,30% in der Kontrollgruppe; p<0,05) sowie Abregulierung beider neointimaler Marker. Aus unseren Ergebnissen schließen wir, dass die Behandlung mit Vardenafil eine neue therapeutische Option für die Behandlung der Restenose darstellen könnte.

Abstract

The long-term results of surgical vessel reconstruction are compromised by restenosis due to neointimal hyperplasia. Recent studies suggest that reduced cyclic guanosine monophosphate signaling may be associated with neointima formation. In a rat model of endarterectomy, we investigated the effect of pharmacological inhibition of cyclic guanosine monophosphate degradation by using the selective phosphodiesterase-5 inhibitor vardenafil. We performed right carotid endarterectomy with endothelial denudation in male rats. There were nine controls, while nine rats received vardenafil (10 mg/kg/d). After 3 weeks of treatment, vessel compartment areas were measured by microscopy using hematoxylin-eosin staining. Immunohistochemical analysis was performed, which demonstrated intensive staining for transforming growth factor-beta 1 and alpha-smooth muscle actin in the control neointima. Vardenafil significantly reduced the stenosis grade (24.64±7.46% vs. 54.12±10.30% in the control group; p<0.05) and the neointimal expression of both markers. Based on our results, treatment with vardenafil can be considered as a new possibility to prevent neointimal hyperplasia after endarterectomy.

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Danksagungen

Der Autor bedankt sich bei seinen Kollegen für die Unterstützung bei Durchführung dieses Projektes. Ein besonderes Dankeschön gilt Herr S. Loganathan und S. Zöllner beim Gestalten des Textes.

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  1. Labor der Experimentellen Herzchirurgie, Universitätsklinikum Heidelberg, INF 326, 69120, Heidelberg, Deutschland

    K. Hirschberg

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Correspondence to K. Hirschberg.

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Hirschberg, K. Karotis-Endarterektomie in der Ratte. Z Herz- Thorax- Gefäßchir 23, 223–228 (2009). https://doi.org/10.1007/s00398-009-0727-8

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  • DOI: https://doi.org/10.1007/s00398-009-0727-8

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