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

M Zaar; N H Secher; P I Johansson; B Vainer; M Ezban; H Agersø; P L Madsen; N Lomholt; M B Hermit; B Lauritzen

doi:10.1093/bja/aep274

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

M Zaar, N H Secher, P I Johansson, B Vainer, M Ezban, H Agersø, P L Madsen, N Lomholt, M B Hermit, B Lauritzen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

4 Citationer (Scopus)

Abstract

Udgivelsesdato: 2009-Dec

Originalsprog	Engelsk
Tidsskrift	British Journal of Anaesthesia
Vol/bind	103
Udgave nummer	6
Sider (fra-til)	840-7
Antal sider	7
ISSN	0007-0912
DOI	https://doi.org/10.1093/bja/aep274
Status	Udgivet - 2009

Bibliografisk note

Keywords: Animals; Disease Models, Animal; Factor VII; Factor VIIa; Hemorrhage; Hemostatics; Injections, Intramuscular; Injections, Intravenous; Liver; Liver Diseases; Oxygen Consumption; Random Allocation; Recombinant Proteins; Survival Analysis; Sus scrofa; Swine; Swine, Miniature; Treatment Outcome

Adgang til dokumentet

10.1093/bja/aep274

Citationsformater

Effects of a recombinant FVIIa analogue, NN1731, on blood loss and survival after liver trauma in the pig. / Zaar, M; Secher, N H; Johansson, P I; Vainer, B; Ezban, M; Agersø, H; Madsen, P L; Lomholt, N; Hermit, M B; Lauritzen, B.

I: British Journal of Anaesthesia, Bind 103, Nr. 6, 2009, s. 840-7.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

@article{c22d73f0373411df8ed1000ea68e967b,

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

abstract = "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 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg 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 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability of approximately 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.",

author = "M Zaar and Secher, {N H} and Johansson, {P I} and B Vainer and M Ezban and H Agers{\o} and Madsen, {P L} and N Lomholt and Hermit, {M B} and B Lauritzen",

note = "Keywords: Animals; Disease Models, Animal; Factor VII; Factor VIIa; Hemorrhage; Hemostatics; Injections, Intramuscular; Injections, Intravenous; Liver; Liver Diseases; Oxygen Consumption; Random Allocation; Recombinant Proteins; Survival Analysis; Sus scrofa; Swine; Swine, Miniature; Treatment Outcome",

year = "2009",

doi = "10.1093/bja/aep274",

language = "English",

volume = "103",

pages = "840--7",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Oxford University Press",

number = "6",

}

TY - JOUR

T1 - Effects of a recombinant FVIIa analogue, NN1731, on blood loss and survival after liver trauma in the pig

AU - Zaar, M

AU - Secher, N H

AU - Johansson, P I

AU - Vainer, B

AU - Ezban, M

AU - Agersø, H

AU - Madsen, P L

AU - Lomholt, N

AU - Hermit, M B

AU - Lauritzen, B

N1 - Keywords: Animals; Disease Models, Animal; Factor VII; Factor VIIa; Hemorrhage; Hemostatics; Injections, Intramuscular; Injections, Intravenous; Liver; Liver Diseases; Oxygen Consumption; Random Allocation; Recombinant Proteins; Survival Analysis; Sus scrofa; Swine; Swine, Miniature; Treatment Outcome

PY - 2009

Y1 - 2009

N2 - 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 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg 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 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability of approximately 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.

AB - 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 microg kg(-1), n=6; i.m. 540 microg kg(-1), n=4, or 2000 microg 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 microg kg(-1) and i.m. 540 microg kg(-1), with a bioavailability of approximately 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.

U2 - 10.1093/bja/aep274

DO - 10.1093/bja/aep274

M3 - Journal article

C2 - 19808774

VL - 103

SP - 840

EP - 847

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 6

ER -