gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

HyperHaesTM enhances the effect of LF16-0687 on post traumatic edema formation following CCI in rats

HyperHaesTM verstärkt den postiven Effekt von LF16-0687 auf das posttraumatische Hirnödem nach CCI bei der Ratte

Meeting Abstract

  • corresponding author Ulrich-W. Thomale - Klinik für Neurochirurgie, Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
  • M. Griebenow - Klinik für Neurochirurgie, Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
  • D. Pruneau - Laboratoire de Bioanalytique, Fournier /F
  • S.-N. Kroppenstedt - Klinik für Neurochirurgie, Charité, Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
  • A. W. Unterberg - Klinik für Neurochirurgie, Ruprecht-Karls Universität, Heidelberg
  • J. F. Stover - Klinik für Chirurgie, Chirurgische Intensivmedizin, Universitätsklinikum Zürich, Zürich /CH

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocDI.04.05

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0183.shtml

Veröffentlicht: 23. April 2004

© 2004 Thomale 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 vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

The hyperoncotic/hyperosmotic agent HyperHaesTM (HHES) successfully improves post traumatic pericontusional hypoperfusion. We hypothesize that HHES may enhance drug delivery of neuroprotective agents into the cerebral tissue. We investigated the effect of HHES and the bradykinin-2 receptor antagonist LF16-0687 on post traumatic edema and quantified drug concentration in the traumatized hemisphere.

Methods

In 64 male sprague dawley rats, anaesthetized with isoflurane (O2:N2O mixture; 2:1), a moderate cortical contusion was applied to the left parietal cortex using the Controlled Cortical impact injury. LF 16-0687 (10 mg/kg bw), which was injected subcutanously (SC) alone or in combination with HHES (4ml/kg bw) was administered intravenously (IV) 5 minutes following trauma. For placebo administration physiological saline was given accordingly. All animals were subdivided into 6 groups. In group A-D (n=32)posttraumatic edema was quantified gravimetrically at 24 hours following trauma. In group E and F (n=32) the tissue and plasma concentration of LF 16-0687 was quantified using HPLC at 8 and 24 hours following trauma. In group A and E LF 16-0687 and HHES was given in combination. Group B and F received LF 16-0687 alone. In group C only HHES was administered. Group D received placebo IV and SC, respectively.

Results

Water content in the traumatized hemisphere in group A (79.82 ± 0.1%) was reduced versus placebo group D (80.22 ± 0.2%). Only a slight reduction was seen in group B (80 ± 0.2%) and C (79.94 ± 0.1%) in comparison to placebo. The amount of LF 16-0687 concentration in the plasma decreased from 8 to 24 hours. Drug brain tissue concentration increased over time. No significant differences in drug tissue concentration of LF 16-0687 were quantified between groups E (37,1 ± 10 ng/g brain tissue) and F (45.4 ± 18 ng/g brain tissue).

Conclusions

The additive effect of LF 16-0687 and HHES on post traumatic edema does not result from increased cerebral drug concentration. Enhanced pericontusional perfusion does not increase drug delivery of LF 16-0687 to the CNS.