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61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010
Joint Meeting mit der Brasilianischen Gesellschaft für Neurochirurgie am 20. September 2010

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21. - 25.09.2010, Mannheim

Vasorelaxant effect of losartan-potassium in basilar arteries of rats: a new therapeutic approach to prevent cerebral vasospasm?

Meeting Abstract

  • Jürgen Konczalla - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
  • Jan Mrosek - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
  • Stefan Wanderer - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
  • Erdem Güresir - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
  • Volker Seifert - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany
  • Hartmut Vatter - Klinik und Poliklinik für Neurochirurgie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt/Main, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1869

DOI: 10.3205/10dgnc340, URN: urn:nbn:de:0183-10dgnc3406

Veröffentlicht: 16. September 2010

© 2010 Konczalla et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Cerebral vasospasm (CVS) remains to be one of the substantial causes for worse outcome after subarachnoid hemorrhage (SAH). Endothelin-1 (ET-1) is known to play a leading role in the pathophysiological cascade leading to CVS. Clazosentan, an ET-receptor antagonist, is tested in a phase III-study. Some data show a contractile influence of ET-1 to an angiotensin II (ATII)-induced contraction. Therefore, the aim of the present study was to investigate the effect of the ATII-antagonist losartan-potassium (LOS), a save and established drug, to find an additive protective effect to avoid CVS.

Methods: Experimental SAH was induced by a rat double hemorrhage model. Autologous arterial blood was injected into the cisterna magna on day 1 and day 2, in sham operated rats (sham) sodium-chloride solution instead of blood was injected and basilar arteries tested on day 3 (d3) and day 5 (d5) after SAH induction in an organ bath. Concentration-effect curves (CECs) were constructed by cumulative application of ET-1. In rats without SAH (Sham) and after SAH day 3 (d3) and day 5 (d5) we tested the contraction without LOS (LOS-) and under LOS 3x10-4M (LOS+), given 30min prior to the first ET-1 contraction. CECs were compared by the maximum effect (Emax) and the pD2 (mean values [± standard error of the mean]). The pD2 is the negative decadic logarithm of the concentration producing the half maximal effect (-log10_EC50). A p ≤ 0.05 was considered statistically significant (*).

Results: Cumulative application of ET-1 induced a dose-dependent contraction, in controls, sham-operated rats and rats after SAH. The Emax was significantly lower in the LOS+ compared to the LOS- group for sham operated rats (sham LOS-: 118±3%, LOS 3x10-4M: 57±13%*, p<0,001). Also in the SAH groups the Emax was significantly lower in LOS+ versus the LOS- groups (SAH day 3 LOS-: 140±12%, LOS+: 102±6%*, p<0,05; SAH d5 LOS-: 130±8%; LOS+: 95±4%*, p<0,01). The pD2 wasn’t altered significantly, neither in the sham group (LOS-: -7,42; LOS+: -7,79) nor in the SAH-groups (SAH d3 LOS-: -7,64; LOS+: -7,28; SAH d5 LOS-: -7,54; LOS+: -7,63).

Conclusions: The present data indicate that LOS decreases the contractility of rat basilar arteries to ET-1 in control animals and animals after SAH, as an indirect sign for an ATII-dependent influence to an ET-1 induced contraction. The reduced contraction under LOS could be another additive therapeutic approach to prevent CVS after SAH.