Skip Navigation



BJA Advance Access published online on October 6, 2009
British Journal of Anaesthesia, doi:10.1093/bja/aep274
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
103/6/840    most recent
aep274v1
Right arrow E-Letters: Submit a response to the article
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Zaar, M.
Right arrow Articles by Lauritzen, B.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zaar, M.
Right arrow Articles by Lauritzen, B.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2009]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournal.org

Effects of a recombinant FVIIa analogue, NN1731, on blood loss and survival after liver trauma in the pig

M. Zaar1,*, N. H. Secher1, P. I. Johansson2, B. Vainer3, M. Ezban5, H. Agersø5, P. L. Madsen5, N. Lomholt4, M. B. Hermit5 and B. Lauritzen5

1 Department of Anaesthesia
2 Department of Clinical Immunology
3 Department of Pathology
4 Department of Pharmacology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
5 Biopharmaceuticals Research Unit, Novo Nordisk A/S, Måløv, Denmark

* Corresponding author. E-mail: morten.zaar{at}biology.au.dk

Background: We considered whether haemorrhage after a liver trauma would be reduced by early administration of a pro-haemostatic agent and evaluated the effect of i.v. vs i.m. administration of the coagulation factor VIIa analogue NN1731 on haemorrhage after a liver trauma in the pig.

Methods: The pharmacokinetics of i.v. and i.m. NN1731 was evaluated in eight minipigs, and the effects of dose and administration route of NN1731 (i.v. 180 µg kg–1, n=6; i.m. 540 µg kg–1, n=4, or 2000 µg kg–1, n=6) vs vehicle (n=16) were studied on a liver laceration injury in pigs. To simulate a pre-hospital setting, the administration of NN1731 was delayed by 1 min for i.m. administration and 7 min for i.v. administration, at which time fluid resuscitation also began.

Results: In the minipigs, NN1731 exposure was similar after i.v. 180 µg kg–1 and i.m. 540 µg kg–1, with a bioavailability of ~35%. The injury and blood loss at 7 min was comparable between the four groups of pigs; however, after 60 min, the blood loss was lower in the i.v. treated animals: 1.3 (0.3) (i.v.) vs 2.2 (0.8) litres (i.m.540, i.m.2000, and vehicle) (P<0.001). Also, the survival time was increased: 117 (14) (i.v.) vs 84 (28) min (i.m.540, i.m.2000, and vehicle) (P<0.001).

Conclusions: After a liver trauma in the pig, i.v. administration of NN1731 reduced the bleeding and increased the survival time. In contrast, i.m. administration had no effect, presumably because reduced muscle perfusion during haemorrhage reduced the uptake of NN1731.

Keywords: blood, coagulation; complications, haemorrhage; drug delivery; oxygen, uptake; research, animal


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.